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.

Non-interventional Management of Asymptomatic Diminutive Choledocholithiasis Versus Endoscopic Extraction in Consecutive Patients.

BACKGROUND: Current guidelines recommend treating choledocholithiasis, regardless of symptoms or stone size, with endoscopic retrograde cholangiopancreatography (ERCP). However, asymptomatic choledocholithiasis, discovered incidentally on imaging, may carry a higher risk of ERCP-related adverse events, and some asymptomatic and diminutive stones may not cause biliary adverse events during extended follow-up. Therefore, we aimed to clarify the best treatment strategies for asymptomatic choledocholithiasis based on stone size. METHODS: We retrospectively identified patients with incidental imaging-found asymptomatic diminutive (≤ 4 mm) or non-diminutive (> 4 mm) choledocholithiasis and divided them into two groups: those who did not undergo ERCP and were treated when complications arose (on-demand group) and those who underwent ERCP before being symptomatic (intervention group). Adverse events were defined as any biliary or pancreatic complication related to ERCP or arising during observation or after intervention. The primary outcome was the adjusted overall adverse event-free survival using the propensity score-based matching weights method comparing the two groups of stone size. RESULTS: Among 148 patients identified (median follow-up period, 969 days), 68 had diminutive stones and 80 had non-diminutive stones. Of the 68 patients with diminutive stones, 51 were in the on-demand group and 17 in the intervention group. The overall adjusted adverse event-free survival was significantly higher in the on-demand group for diminutive stones (97.4% and 70.1%, respectively, at 3 years; p = 0.01). DISCUSSION: Patients with incidental imaging-detected asymptomatic diminutive choledocholithiasis may benefit from clinical observation, pursuing ERCP when symptoms develop.

Microangiopathic Hemolytic Anemia Is a Late and Fatal Complication of Gastric Signet Ring Cell Carcinoma: A Systematic Review and Case-Control Study.

BACKGROUND: Microangiopathic hemolytic anemia (MAHA) is a rare paraneoplastic syndrome that has been reported in patients with gastric signet ring cell carcinoma (SRCC). Clinical and prognostic features of MAHA in this setting have been poorly described. MATERIALS AND METHODS: We conducted a systematic review in 8 databases of gastric SRCC complicated by MAHA and performed a case-control study assessing factors associated with survival in patients with gastric SRCC and MAHA in our pooled cohort compared with age-, sex-, and stage-matched cases of gastric SRCC from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive analyses were performed and multivariable Cox-proportional hazards regression modeling was used to determine factors associated with overall survival. RESULTS: All identified patients (n = 47) were symptomatic at index presentation, commonly with back/bone pain, and dyspnea. Microangiopathic hemolytic anemia was the first manifestation of gastric SRCC in 94% of patients. Laboratory studies were notable for anemia (median 7.7 g/dL), thrombocytopenia (median 45.5 × 103/µL), and hyperbilirubinemia (median 2.3 mg/dL). All patients with MAHA had metastatic disease at presentation, most often to the bone, bone marrow, and lymph nodes. Median survival in patients with gastric SRCC and MAHA was significantly shorter than a matched SEER-derived cohort with metastatic gastric SRCC (7 weeks vs 28 weeks, P < .01). In multivariate analysis, patients with MAHA were at significantly increased risk of mortality (HR 3.28, 95% CI 2.11-5.12). CONCLUSION: Microangiopathic hemolytic anemia is a rare, late-stage complication of metastatic gastric SRCC and is associated with significantly decreased survival compared with metastatic gastric SRCC alone.

A single center randomized double blind controlled trial of pentoxifylline in acute pancreatitis: Challenges and opportunities.

OBJECTIVES: Despite substantial morbidity and mortality associated with acute pancreatitis (AP), only one small randomized controlled drug trial (RCT) is available in the past few decades from the United States. Hence, we conducted a single-center, double-blind, placebo-controlled RCT of pentoxifylline in AP. METHODS: A total of 9 doses of oral pentoxifylline 400 mg or placebo tablet, three times daily, was administered within 72 h of diagnosis, using randomization blocks by pharmacy. Primary outcome was a composite outcome including any of the following: death, peripancreatic and/or pancreatic necrosis, infected pancreatic necrosis, persistent organ failure, persistent systemic inflammatory response syndrome, hospital stay longer than 4 days, need for intensive care, and need for intervention for necrosis. RESULTS: Between July 7, 2015, and April 4, 2017, we identified 685 patients with AP, 233 met eligibility criteria and 176 were approached for the study. Of these, 91 (51.7%) declined and finally 45 in pentoxifylline group and 38 in placebo group (83 total) were compared. There were no significant differences in primary outcome (27 [60.0%] vs 15 [39.5%]; P = .06). Pentoxifylline group was not associated with any benefit, but withlonger stay (42% vs. 21%; P = .04) and higher readmission rates (16 %vs 3%; P = .047). CONCLUSIONS: We could not demonstrate superiority of pentoxifylline over placebo. Smaller sample size and inclusion of all types of severity might be the reasons for lack of efficacy. The challenges observed in the present study indicate that, in order to conduct a successful drug trial in AP, a multi center collaboration is essential.

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.

Horibe GI bleeding prediction score: a simple score for triage decision-making in patients with suspected upper GI bleeding.

BACKGROUND AND AIMS: Although upper GI bleeding (UGIB) is a significant cause of inpatient admissions, no scoring method has proven to be accurate and simple as a standard for triage purposes. Therefore, we compared a previously described 3-variable score (1 point each for absence of daily proton pump inhibitor use in the week before the index presentation, shock index [heart rate/systolic blood pressure] ≥1, and blood urea nitrogen/creatinine ≥30 [urea/creatinine≥140]), the Horibe gAstRointestinal BleedING scoRe (HARBINGER), with the 8-variable Glasgow-Blatchford Score (GBS) and 5-variable AIMS65 to evaluate and validate the accuracy in predicting high-risk features that warrant admission and urgent endoscopy. METHODS: Consecutive patients presenting with suspected UGIB between 2012 and 2015 were prospectively enrolled in 3 acute care Japanese hospitals. On presentation to the emergency setting, an endoscopy was performed in a timely fashion. The primary outcome was the prediction of high-risk endoscopic stigmata. RESULTS: Of 1486 enrolled patients, 637 (43%) harbored high-risk endoscopic stigmata according to international consensus statements. The area under the receiver operating characteristic curve (AUC) for the HARBINGER was .76 (95% confidence interval [CI], .72-.79), which was significantly superior to both the GBS (AUC, .68; 95% CI, .64-.71; P < .001) and the AIMS65 (AUC, .54; 95% CI, .50-.58; P < .001). When the HARBINGER cutoff value was set at 1 to rule out patients who needed admission and urgent endoscopy, its sensitivity and specificity was 98.8% (95% CI, 97.9-99.6) and 15.5% (95% CI, 13.1-18.0), respectively. CONCLUSIONS: The HARBINGER, a simple 3-variable score, provides a more accurate method for triage of patients with suspected UGIB than both the GBS and AIMS65.

Impact of electrical pulse cut mode during endoscopic papillectomy: Pilot randomized clinical trial.

OBJECTIVE: Endoscopic papillectomy is increasingly being used for ampullary adenoma treatment. However, it remains challenging despite increased safety with treatment advances. The ideal power output and electrosurgical current mode for mucosal resection are not established. We aimed to identify the ideal electrical pulse for use during resection. METHODS: This pilot randomized, single-blind, prospective, multicenter trial, recruited patients with ampullary adenomas and conventional anatomy who were scheduled to undergo endoscopic papillectomy. Endoscopic treatment was performed using a standardized algorithm and patients were randomized for endoscopic papillectomy with Endocut or Autocut. The primary outcome was the incidence of delayed bleeding. Incidence of procedure-related pancreatitis, successful complete resection, pathological findings, and other adverse events were secondary endpoints. RESULTS: Sixty patients were enrolled over a 2-year period. The incidences of delayed bleeding (13.3% vs. 16.7%, P = 1.00) and pancreatitis (27% vs. 30%, P = 0.77) were similar between both groups. The rate of crush artifacts was higher in the Endocut than in the Autocut group (27% vs. 3.3%, P = 0.03). Immediate bleeding when resecting tumors greater than 14 mm in diameter was more common in the Autocut than in the Endocut group (88% vs. 46%, P = 0.04). CONCLUSIONS: The Autocut and Endocut modes have similar efficacy and safety for endoscopic papillectomy. The Endocut mode may prevent immediate bleeding in cases with large tumor sizes, although it causes more frequent crush artifacts. REGISTRY AND THE REGISTRATION NUMBER: The Japanese UMIN Clinical Trials Registry (UMIN-CTR: 000021382).

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.

Successful management of bile duct injury with duodenal perforation using endoscopic naso-pancreatic drainage and fully covered self-expandable metallic stent deployment.

Video 1A case of bile and pancreatic duct injury with duodenal perforation during endoscopic submucosal dissection for superficial duodenal epithelial neoplasia.

Normal saline versus Ringer's solution and critical-illness mortality in acute pancreatitis: a nationwide inpatient database study.

BACKGROUND: Fluid resuscitation is fundamental in acute pancreatitis (AP) treatment. However, the optimal choice between normal saline (NS) and Ringer's solution (RS), and its impact on mortality in critically ill patients, remains controversial. This retrospective cohort study, utilizing a national Japanese inpatient database, investigates this question. METHODS: Using the Japanese Diagnosis Procedure Combination database between July 2010 and March 2021, we identified adult patients hospitalized in intensive care units (ICU) or high-dependency care units (HDU) for AP who survived at least three days and received sufficient fluid resuscitation (≥ [10 ml/kg/hr*1 h + 1 ml/kg/hr*71 h] ml) within three days of admission including emergency room infusions. Patients were classified into groups based on the predominant fluid type received: the NS group (> 80% normal saline) and the RS group (> 80% Ringer's solution). Propensity score matching was employed to reduce potential confounding factors and facilitate a balanced comparison of in-hospital mortality between the two groups. RESULTS: Our analysis included 8710 patients with AP. Of these, 657 (7.5%) received predominantly NS, and 8053 (92.5%) received predominantly RS. Propensity score matching yielded 578 well-balanced pairs for comparison. The NS group demonstrated significantly higher in-hospital mortality than the RS group (12.8% [474/578] vs. 8.5% [49/578]; risk difference, 4.3%; 95% confidence interval, 0.3% to 8.3%). CONCLUSIONS: In patients admitted to ICU or HDU with AP receiving adequate fluid resuscitation, RS can be a preferred infusion treatment compared to NS.

Risk of Syndrome-Associated Cancers Among First-Degree Relatives of Patients With Pancreatic Ductal Adenocarcinoma With Pathogenic or Likely Pathogenic Germline Variants.

Importance: Increased cancer risk in first-degree relatives of probands with pancreatic ductal adenocarcinoma (PDAC probands) who carry pathogenic or likely pathogenic germline variants (PGVs) in cancer syndrome-associated genes encourages cascade genetic testing. To date, unbiased risk estimates for the development of cancers on a gene-specific basis have not been assessed. Objective: To quantify the risk of development of PDAC and extra-PDAC among first-degree relatives of PDAC probands who carry a PGV in 1 of 9 cancer syndrome-associated genes-ATM, BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2, and CDKN2A. Design, Setting, and Participants: This case series focused on first-degree relatives of PDAC probands carrying PGVs in specific cancer syndrome-associated genes. The cohort comprised clinic-ascertained patients enrolled in the Mayo Clinic Biospecimen Resource for Pancreas Research registry with germline genetic testing. In total, 234 PDAC probands carrying PGVs were drawn from the prospective research registry of 4562 participants who had undergone genetic testing of cancer syndrome-associated genes. Demographic and cancer-related family histories were obtained by questionnaire. The data were collected from October 1, 2000, to December 31, 2021. Main Outcomes and Measures: For the PDAC probands, the genetic test results of the presence of PGVs in 9 cancer syndrome-associated genes were obtained by clinical testing. Cancers (ovary, breast, uterus or endometrial, colon, malignant melanoma, and pancreas) among first-degree relatives were reported by the probands. Standardized incidence ratios (SIRs) were used to estimate cancer risks among first-degree relatives of PDAC probands carrying a PGV. Results: In total, 1670 first-degree relatives (mean [SD] age, 58.1 [17.8] years; 853 male [51.1%]) of 234 PDAC probands (mean [SD] age, 62.5 [10.1] years; 124 male [53.0%]; 219 [94.4%] White; 225 [98.7%] non-Hispanic or non-Latino]) were included in the study. There was a significantly increased risk of ovarian cancer in female first-degree relatives of probands who had variants in BRCA1 (SIR, 9.49; 95% CI, 3.06-22.14) and BRCA2 (SIR, 3.72; 95% CI, 1.36-8.11). Breast cancer risks were higher with BRCA2 variants (SIR, 2.62; 95% CI, 1.89-3.54). The risks of uterine or endometrial cancer (SIR, 6.53; 95% CI, 2.81-12.86) and colon cancer (SIR, 5.83; 95% CI, 3.70-8.75) were increased in first-degree relatives of probands who carried Lynch syndrome mismatch repair variants. Risk of PDAC was also increased for variants in ATM (SIR, 4.53; 95% CI, 2.69-7.16), BRCA2 (SIR, 3.45; 95% CI, 1.72-6.17), CDKN2A (SIR, 7.38; 95% CI, 3.18-14.54), and PALB2 (SIR, 5.39; 95% CI, 1.45-13.79). Melanoma risk was elevated for first-degree relatives of probands with CDKN2A variants (SIR, 7.47; 95% CI, 3.97-12.77). Conclusions and Relevance: In this case series, the presence of PGVs in 9 cancer syndrome-associated genes in PDAC probands was found to be associated with increased risk of 6 types of cancers in first-degree relatives. These gene-specific PDAC and extra-PDAC cancer risks may provide justification for clinicians to counsel first-degree relatives about the relevance and importance of genetic cascade testing, with the goal of higher uptake of testing.

Successful radiotherapy for recurrent obstructive pancreatitis secondary to pancreatic metastasis from cervical squamous-cell carcinoma.

Metastatic pancreatic cancer is a rare condition and cases of pancreatic metastasis from cervical cancer are infrequently reported. Furthermore, the incidence rates of pancreatic tumors as the cause of pancreatitis and of pancreatitis in patients with pancreatic tumors are similarly low. Pancreatitis may occur when a tumor obstructs the pancreatic duct. This condition may be difficult to manage and significantly reduces the quality of life because of severe abdominal pain. Here, we present a rare case of obstructive pancreatitis caused by pancreatic metastasis from cervical squamous-cell carcinoma, pathologically confirmed using endoscopic ultrasonography-guided fine-needle biopsy and treated with palliative irradiation to achieve rapid therapeutic relief. It is important to obtain appropriate tissue samples, confirm the pathological diagnosis, and compare the pathological findings with those of the primary tumor to select the appropriate treatment for obstructive pancreatitis caused by a metastatic pancreatic tumor.

Association between computerized tomography (CT) study of body composition and severity of acute pancreatitis: Use of a novel Z-score supports obesity paradox.

BACKGROUND & AIMS: The association between body composition parameters measured on computed tomography (CT) and severity of acute pancreatitis (AP) is conflicting because these composition parameters vary considerably by sex and age. We previously developed normative body composition data, in healthy subjects. Z-score calculated from the normative data gives age and sex adjusted body composition parameters. We studied the above association using this novel Z-score in a large cohort of patients with AP. METHODS: Between January 2014 and March 2018, patients admitted with AP and had CT scans within a week of admission, were enrolled. Body composition data including skeletal muscle (SM), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were calculated from the CT scan using deep learning automated algorithm. Then we converted the value to Z-score, and then compared the same score between mild AP, moderately severe AP and severe AP defined by revised Atlanta criteria. RESULTS: Out of 514 patients, 336 (65.4%) are mild AP, 130 (25.3%) moderately severe AP, and 48 (9.3%) severe AP. Patients with moderately severe AP had significantly lower SM-z-score than those with mild AP (1.21 vs1.73, p = 0.048) and patients with severe AP had significantly lower SAT-z-score than those with mild AP (0.70 vs.1.29, p = 0.016). VAT-z-score was not significantly different between three groups. (p = 0.76). CONCLUSION: Lower SM-z-score and SAT-z-score were associated with moderately severe and severe types of AP, respectively. Future prospective studies in patients with AP using Z-scores, may define the association between body composition and severity of AP, and explain the inconsistencies reported in previous studies.

Endoscopic Ultrasound-Guided Sampling for Personalized Pancreatic Cancer Treatment.

Pancreatic cancer is the most lethal solid malignancy, and the number of patients with pancreatic cancer is increasing. Systemic chemotherapies are often ineffective for such patients, and there is an urgent need for personalized medicine. Unlike other types of cancer, personalized treatments for pancreatic cancer are still in development. Consequently, pancreatic cancer is less sensitive to anticancer drugs and is often refractory to common treatments. Therefore, advances in personalized medicine for pancreatic cancer are necessary. This review examined advances in personalized medicine for pancreatic cancer, including the use of endoscopic ultrasound (EUS)-guided sampling. EUS-guided sampling is widely used for diagnosing pancreatic tumors and is expected to be applied to sampled tissues. Additionally, there has been an increase in clinical research using EUS-guided sampling. The combination of precision medicine using genomic testing and pharmacological profiles based on high-throughput drug sensitivity testing using patient-derived organoids is expected to revolutionize pancreatic cancer treatment.

Endoscopic Diagnosis of Biliary Stricture Combined with Digital Cholangioscope: A Case Series.

The endoscopic diagnosis of biliary tract lesions is applied as a non-invasive method; however, its diagnostic accuracy is not yet high. Moreover, digital cholangioscopy is used for directly visualizing the inside of the bile duct, resulting in a more precise biopsy. We present the case series of the outcomes of diagnosis using digital cholangioscopy in patients who underwent cholangioscopy for the evaluation of biliary stenosis in our department between January 2014 and March 2021. The controls were those who underwent a biopsy for biliary stenosis with conventional endoscopic retrograde cholangiopancreatography (ERCP). Background data for each case were collected, and the clinical outcomes by biopsy were evaluated, focusing on the accuracy of the diagnosis. Cholangioscopy was performed in 15 cases, while a conventional biopsy by ERCP was performed in 172 cases. Nine of 15 cases (60.0%) were diagnosed with cholangiocarcinoma. The number of specimens obtained through conventional ERCP and cholangioscopy was 2.5 ± 1.3 and 3.3 ± 1.5, respectively (p = 0.043). The diagnostic accuracy of conventional ERCP and cholangioscopy were 65.7% (113 of 172 cases) and 100%, respectively, which was significantly higher in the group with cholangioscopy. Digital cholangioscopy is useful when the diagnosis of the biliary stricture using the conventional ERCP method is difficult.