Details of a Researcher - Horibe, Masayasu

Papers - Horibe, Masayasu

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Discordant risk factors between pancreatic neuroendocrine neoplasms and pancreatic ductal adenocarcinoma

Chandra S., Halfdanarson T.R., Carlson E.E., Rabe K.G., Mahipal A., Majumder S., Bamlet W.R., Horibe M., Tella S.H., Shariq O., Carr R.M., Cleary S.P., Oberg A.L., Antwi S.O.

Endocrine Related Cancer 32 ( 4 ) 2025.04

ISSN 13510088

Pancreatic neuroendocrine neoplasm (panNEN) is a rare malignancy and the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma (PDAC), but its etiology is poorly understood. We investigated whether the risk factors of panNEN are concordant with those known for PDAC. We performed the largest case-control study to date on panNENs, comprising 927 sporadic nonfunctional panNEN cases and 1807 frequency-matched controls, using data from the Mayo Clinic Biospecimen Resource for Pancreas Research. We assessed associations for obesity, first-degree family history of pancreatic cancer, cigarette smoking, overall type II diabetes mellitus (T2DM), new-onset T2DM (<1 year before panNEN diagnosis), longstanding T2DM (≥5 years), alcohol intake and aspirin use. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs). Our results show that overall T2DM (OR = 1.71, 95% CI: 1.37–2.14) and new-onset T2DM (OR = 2.65, 95% CI: 1.92–3.69) are associated with higher odds of panNEN, but not longstanding T2DM (OR = 1.29, 95% CI: 0.94–1.75). A non-significant elevated odds of panNEN was observed among participants with a positive family history of pancreatic cancer (OR = 1.44, 95% CI: 0.96–2.14). Alcohol use was inversely related to panNEN (OR = 0.52, 95% CI: 0.42–0.66, ever-vs-never). No association was observed for smoking, obesity or aspirin use. These findings indicate that overall T2DM and new-onset T2DM are associated with higher odds of panNEN. Unlike PDAC, alcohol use was inversely related to panNEN, and we found no associations for cigarette smoking, obesity or aspirin use. These results indicate differences in the risk factor profiles of panNEN and PDAC.

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Feasibility of endoscopic submucosal dissection including papilla (with video)

Yahagi N., Takatori Y., Sasaki M., Imura Y., Murata S., Sato T., Minezaki D., Hayakawa T., Nakajima Y., Okada H., Sakurai H., Tojo A., Iwata K., Miyazaki K., Kayashima A., Masunaga T., Mizutani M., Akimoto T., Seino T., Kawasaki S., Horibe M., Fukuhara S., Matsuura N., Sujino T., Nakayama A., Takabayashi K., Iwasaki E., Kato M.

Digestive Endoscopy 37 ( 4 ) 402 - 410 2025.04

ISSN 09155635

Objectives: Endoscopic papillectomy (EP) is a low-invasive treatment for duodenal tumors including papilla. The limit of lesion size and local recurrence have been issues in EP. We developed endoscopic submucosal dissection (ESD) for the duodenal tumors including papilla (ESDIP: ESD including papilla) to overcome the problems. The aim of this study was to evaluate the feasibility of ESDIP. Methods: We included the patients who underwent ESDIP from August 2010 to January 2024 in this study. We evaluated the retrospective characteristics of patients and lesions, clinical results of ESDIP and of endoscopic retrograde cholangiopancreatography (ERCP) as prevention for delayed adverse events, and pathological findings. We also calculated the cumulative recurrence rate and overall survival rate at 12 months after ESDIP. Results: Fifty-four patients were included in this study. The mean lesion size was 39 mm. The third-quarter cases revealed a less than half-circumferential lesion, and the one case with a full-circumferential lesion. Resection was accomplished in 96% (n = 52), and also the en-bloc resection rate was 96%. Of the cases in accomplished resection, 98% of patients were intubated with a pancreaticobiliary drainage tube by ERCP. Intraprocedural perforation occurred in eight cases. Delayed bleeding occurred in 10 cases. Delayed perforation was seen only in one case. The incidence of post-ERCP pancreatitis was 25%. Cumulative local recurrence rate and the overall survival rate were 15% and 96%, respectively. Conclusion: ESDIP may be feasible for duodenal tumors including papilla, and is a potential alternative option to avoid pancreaticoduodenectomy.

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Evaluation of a novel contrast-enhanced fluoroscopy protocol for endoscopic retrograde cholangiopancreatography in a phantom model (with video)

Hayakawa T., Horibe M., Iwasaki E., Bazerbachi F., Suno Y., Sato T., Okada H., Nakajima Y., Mizukami Y., Kayashima A., Seino T., Kawasaki S., Kanai T.

Den Open 5 ( 1 ) 2025.04

Objectives: This study evaluated a novel contrast-enhanced (CE) fluoroscopy protocol for endoscopic retrograde cholangiopancreatography, which optimizes image processing to enhance contrast of devices and contrast media. We compared the CE protocol with the conventional standard protocol to assess its potential for reducing radiation exposure while improving image visibility. Methods: The study utilized a multidirectional fluoroscopy unit and phantoms to evaluate the new CE protocol against the conventional protocol. Comparisons included radiation dose rates, spatial resolution, and concentration resolution under various fluoroscopic conditions. The investigation aimed to determine if the CE protocol offered improved visibility while potentially reducing radiation exposure. Results: Three CE protocol modes (LOW-7.5 fps, MID-3.75 fps, and LOW-3.75 fps) achieved lower dose rates than the standard MID-7.5 fps mode commonly used in clinical practice. Dynamic spatial resolution was significantly superior in all three CE modes compared to the standard protocol (p < 0.0167). Static spatial resolution did not differ significantly between protocols. Only the CE MID-3.75 fps mode showed superior concentration resolution compared to the standard protocol (p < 0.00833). Conclusions: The novel CE fluoroscopy protocol provides superior dynamic spatial resolution in endoscopic retrograde cholangiopancreatopgraphy while reducing radiation exposure, potentially enhancing procedure guidance and safety for both patients and clinicians.

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Bodyweight-Adjusted Nonsteroidal Anti-inflammatory Drugs Dose in the Prevention of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis

Kayashima A., Horibe M., Iwasaki E., Bazerbachi F., Kawasaki S., Kanai T.

Pancreas 54 ( 3 ) e188 - e193 2025.03

ISSN 08853177

Objectives: Although rectal nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence of postendoscopic retrograde cholangiopancreatography pancreatitis (PEP), their optimal dosage is unknown. Given possible interindividual variability in the pharmacodynamics of NSAIDs, we hypothesized that the dose required to achieve adequate PEP prophylaxis varies with body weight. Materials and Methods: We conducted an analysis using single-center, prospective, observational cohort study data. The primary outcome was PEP incidence by NSAID dosage per body weight (mg/kg). Patients meeting the inclusion criteria were classified into 3 groups. Results: We included 891 patients, with 400, 454, and 37 patients in the control group with no NSAID therapy, the NSAID <1.0 mg/kg group, and the NSAID ≥1.0 mg/kg group, respectively. In the adjusted cohort, the odds ratio of PEP was 0.18 (95% confidence interval: 0.041–0.79; P = 0.023) for NSAID ≥1.0 mg/kg and 1.3 (95% confidence interval: 0.76–2.3; P = 0.31) for NSAID <1.0 mg/kg compared to the control group without NSAID. Conclusions: PEP was not prevented by NSAID dosages below 1.0 mg/ kg body weight whereas a dosage above 1.0 mg/kg body weight had a significant prophylactic effect. An NSAID dosage adjusted to body weight may be necessary to achieve an adequate prophylactic effect against PEP.

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Capnographic monitoring using a novel mainstream system during endoscopic ultrasound and endoscopic retrograde cholangiopancreatography: A prospective randomized controlled trial

Takimoto Y., Iwasaki E., Horibe M., Fukuhara S., Minami K., Kawasaki S., Masaoka T., Ogata H., Bazerbachi F., Kanai T.

Journal of Hepato Biliary Pancreatic Sciences 32 ( 3 ) 254 - 263 2025.03

ISSN 18686974

Background/Purpose: Insufficient studies exist on capnography efficacy during endoscopic ultrasound or endoscopic retrograde cholangiopancreatography, and no definitive conclusions have been drawn. To evaluate the feasibility and efficacy of a novel mainstream capnography using an over-the-biteblock end-tidal CO<inf>2</inf> (EtCO<inf>2</inf>) detector in decreasing the risk of hypoxemia during endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). Methods: Patients undergoing EUS or ERCP with conscious sedation at a single Japanese center were randomized to a control or a novel capnography monitored (intervention) group in a 1:1 ratio. Hypoxemia correction maneuvers were pursued if the oxygen saturation decreased to <92% in the control or intervention group and if a 15-s suspension of EtCO<inf>2</inf> wave occurred in the intervention group. The primary outcome was the incidence of hypoxemic events, defined as oxygen saturation <90%, during the procedures. Secondary outcomes included technical feasibility of EUS and ERCP with the use of this novel over-the-biteblock monitor. Results: In total, 250 patients were enrolled without dropouts or missing data (control group: 125; capnography group: 125). There was no significant difference in the incidence of hypoxemia between the control and capnography groups (29.6% [37/125] vs. 26.4% [33/125]; p =.573). The estimated odds ratio was 0.925 (95% confidence interval: 0.708–1.208). The EtCO<inf>2</inf> concentration was successfully captured without impeding endoscopic maneuvers from the beginning to the end of the procedure in all patients. Conclusions: Although the novel mainstream capnography with an over-the-biteblock EtCO<inf>2</inf> detector captures the EtCO<inf>2</inf> concentration in EUS or ERCP under conscious sedation, it does not lead to the prevention of hypoxemia.

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

Horibe M., Kayashima A., Ohbe H., Bazerbachi F., Mizukami Y., Iwasaki E., Matsui H., Yasunaga H., Kanai T.

Journal of Intensive Care 12 ( 1 ) 2024.12

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.

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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

Yamamoto T., Horibe M., Sanui M., Sasaki M., Mizobata Y., Esaki M., Sawano H., Goto T., Ikeura T., Takeda T., Oda T., Yasuda H., Namiki S., Miyazaki D., Kitamura K., Chiba N., Ozaki T., Yamashita T., Oshima T., Hirota M., Moriya T., Shirai K., Yamamoto S., Kobayashi M., Saito K., Saito S., Iwasaki E., Kanai T., Mayumi T.

Pancreatology 24 ( 6 ) 827 - 833 2024.09

ISSN 14243903

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.

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Efficacy of a novel ultra-tapered endoscopic nasobiliary drainage tube in gallbladder drainage

Hayakawa T., Iwasaki E., Okada H., Nakajima Y., Kayashima A., Kawasaki S., Horibe M., Kanai T.

Videogie 9 ( 4 ) 208 - 210 2024.04

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

Okada H., Iwasaki E., Fukuhara S., Horibe M., Sasaki M., Kanai T., Yahagi N., Kato M.

Videogie 9 ( 3 ) 154 - 157 2024.03

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

Kayashima A., Horibe M., Iwasaki E., Bazerbachi F., Okada H., Nakajima Y., Mizukami Y., Machida Y., Kawasaki S., Kitago M., Kanai T.

Digestive Diseases and Sciences 68 ( 12 ) 4456 - 4465 2023.12

ISSN 01632116

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.

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

Nakajima Y., Iwasaki E., Kayashima A., Machida Y., Kawasaki S., Horibe M., Kawaida M., Masugi Y., Iwata T., Kanai T.

Clinical Journal of Gastroenterology 16 ( 5 ) 755 - 760 2023.10

ISSN 18657257

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.

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Risk of Syndrome-Associated Cancers among First-Degree Relatives of Patients with Pancreatic Ductal Adenocarcinoma with Pathogenic or Likely Pathogenic Germline Variants

Chen X., Meyer M.A., Kemppainen J.L., Horibe M., Chandra S., Majumder S., Petersen G.M., Rabe K.G.

JAMA Oncology 9 ( 7 ) 955 - 961 2023

ISSN 23742437

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.

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

Lam R., Tarangelo N., Wang R., Horibe M., Grimshaw A.A., Jain D., Haffar S., Bazerbachi F., Kunz P.L., Li D.K.

Oncologist 27 ( 9 ) 751 - 759 2022.09

ISSN 10837159

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 × 10<sup>3</sup>/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.

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

Horibe M., Takahashi N., Weston A.D., Philbrick K., Yamamoto S., Takahashi H., Vege S.S.

Clinical Nutrition 41 ( 8 ) 1676 - 1679 2022.08

ISSN 02615614

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.

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

Fukuhara S., Iwasaki E., Kayashima A., Machida Y., Tamagawa H., Kawasaki S., Horibe M., Hori S., Abe Y., Kitago M., Ogata H., Kanai T.

Healthcare (Switzerland) (Healthcare (Switzerland)) 10 ( 1 ) 2022.01

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.

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Current issue of management of post ERCP pancreatitis

Iwasaki E., Horibe M., Kanai T.

Journal of Japanese Society of Gastroenterology 119 ( 8 ) 733 - 743 2022

ISSN 04466586

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Superiority of urgent vs early endoscopic hemostasis in patients with upper gastrointestinal bleeding with high-risk stigmata

Horibe M., Iwasaki E., Matsuzaki J., Bazerbachi F., Kaneko T., Minami K., Fukuhara S., Masaoka T., Hosoe N., Ogura Y., Namiki S., Hosoda Y., Ogata H., Kanai T.

Gastroenterology Report 9 ( 6 ) 543 - 551 2021.12

Background Guidelines recommend that all patients with upper gastrointestinal bleeding (UGIB) undergo endoscopy within 24 h. It is unclear whether a subgroup may benefit from an urgent intervention. We aimed to evaluate the influence of endoscopic hemostasis and urgent endoscopy on mortality in UGIB patients with high-risk stigmata (HRS). Methods Consecutive patients with suspected UGIB were enrolled in three Japanese hospitals with a policy to perform endoscopy within 24 h. The primary outcome was 30-day mortality. Endoscopic hemostasis and endoscopy timing (urgent, ≤6 h; early, >6 h) were evaluated in a regression model adjusting for age, systolic pressure, heart rate, hemoglobin, creatinine, and variceal bleeding in multivariate analysis. A propensity score of 1:1 matched sensitivity analysis was also performed. Results HRS were present in 886 of 1966 patients, and 35 of 886 (3.95%) patients perished. Median urgent-endoscopy time (n = 769) was 3.0 h (interquartile range [IQR], 2.0–4.0 h) and early endoscopy (n = 117) was 12.0 h (IQR, 8.5–19.0 h). Successful endoscopic hemostasis and urgent endoscopy were significantly associated with reduced mortality in multivariable analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09–0.52; P = 0.0006, and OR, 0.37; 95% CI, 0.16–0.87; P = 0.023, respectively). In a propensity-score-matched analysis of 115 pairs, adjusted comparisons showed significantly lower mortality of urgent vs early endoscopy (2.61% vs 7.83%, P < 0.001). Conclusions A subgroup of UGIB patients, namely those harboring HRS, may benefit from endoscopic hemostasis and urgent endoscopy rather than early endoscopy in reducing mortality. Implementing triage scores that predict the presence of such lesions is important.

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Diagnosing Biliary Strictures: Distinguishing IgG4-Related Sclerosing Cholangitis From Cholangiocarcinoma and Primary Sclerosing Cholangitis

Hori Y., Chari S.T., Tsuji Y., Takahashi N., Inoue D., Hart P.A., Uehara T., Horibe M., Yamamoto S., Satou A., Zhang L., Notohara K., Naitoh I., Nakazawa T.

Mayo Clinic Proceedings Innovations Quality and Outcomes 5 ( 3 ) 535 - 541 2021.06

Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)–related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography–related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4–SC from cholangiocarcinoma and/or primary SC.

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

Nakashima I., Horibe M., Sanui M., Sasaki M., Sawano H., Goto T., Ikeura T., Takeda T., Oda T., Yasuda H., Ogura Y., Miyazaki D., Kitamura K., Chiba N., Ozaki T., Yamashita T., Koinuma T., Oshima T., Yamamoto T., Hirota M., Moriya T., Shirai K., Izai J., Takeda K., Sekino M., Iwasaki E., Kanai T., Mayumi T.

Pancreas (Pancreas) 50 ( 3 ) 371 - 377 2021.03

ISSN 08853177

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.

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Endoscopic ultrasound-guided sampling for personalized pancreatic cancer treatment

Iwasaki E., Fukuhara S., Horibe M., Kawasaki S., Seino T., Takimoto Y., Tamagawa H., Machida Y., Kayashima A., Noda M., Hayashi H., Kanai T.

Diagnostics (Diagnostics) 11 ( 3 ) 2021.03

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.

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Verrucous esophageal carcinoma is a unique indolent subtype of squamous cell carcinoma: a systematic review and individual patient regression analysis

Li D.K., Haffar S., Horibe M., Homsi H.A., Zukerberg L., Murad M.H., Visrodia K.H., Gala M., Katzka D.A., Bazerbachi F.

Journal of Gastroenterology (Journal of Gastroenterology) 56 ( 1 ) 12 - 24 2021.01

ISSN 09441174

Background and aims: Verrucous esophageal carcinoma (VEC) is a rare malignancy that presents a diagnostic challenge. We aim to characterize the clinical and genomic features, tumor behavior, and treatment outcomes of VEC to guide clinical practice. Methods: We performed a systematic review of the literature and identified additional cases from Massachusetts General Hospital records and The Cancer Genome Atlas (TCGA). We obtained individual VEC patient data and analyzed publicly available clinicogenomic data from TCGA. We performed a regression analysis comparing cases of VEC to esophageal squamous cell carcinoma (ESCC) to identify factors influencing survival. Results: A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol). Symptoms were present at diagnosis in 95% of patients, most commonly dysphagia and weight loss. Median symptom onset to diagnosis time was 11.5 months with frequent misdiagnosis as Candida esophagitis. Among VEC cases with pathologic staging, lymph node metastases were rare (5%) compared to ESCC (40%). VEC was genomically characterized by enrichment of SMARCA4 missense mutations and a lack of pathogenic TP53 mutations. Despite its diagnostic elusiveness, in a multivariate regression analysis, VEC was detected at earlier stages (p = < 0.001) compared to ESCC, and advanced stage was the only significant factor affecting survival (p = 0.013). Conclusions: VEC is a rare, clinically and genomically distinct subtype of ESCC. Recognition and diagnosis of this lesion may allow the pursuit of curative and less morbid treatment strategies.

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

Vege S.S., Horibe M., Chari S.T., Clemens M.A., Loftus C.G., Enders F.T.

Pancreatology (Pancreatology) 20 ( 8 ) 1592 - 1597 2020.12

ISSN 14243903

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.

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

Minami K., Horibe M., Sanui M., Sasaki M., Iwasaki E., Sawano H., Goto T., Ikeura T., Takeda T., Oda T., Yasuda H., Ogura Y., Miyazaki D., Kitamura K., Chiba N., Ozaki T., Yamashita T., Koinuma T., Oshima T., Yamamoto T., Hirota M., Tokuhira N., Azumi Y., Nagata K., Takeda K., Furuya T., Lefor A.K., Mayumi T., Kanai T.

Journal of Gastrointestinal Surgery (Journal of Gastrointestinal Surgery) 24 ( 9 ) 2037 - 2045 2020.09

ISSN 1091255X

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.

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

Horibe M., Iwasaki E., Bazerbachi F., Kaneko T., Matsuzaki J., Minami K., Masaoka T., Hosoe N., Ogura Y., Namiki S., Hosoda Y., Ogata H., Chan A.T., Kanai T.

Gastrointestinal Endoscopy (Gastrointestinal Endoscopy) 92 ( 3 ) 578 - 588.e4 2020.09

ISSN 00165107

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.

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Efficacy and safety of immediate oral intake in patients with mild acute pancreatitis: A randomized controlled trial

Horibe M., Iwasaki E., Nakagawa A., Matsuzaki J., Minami K., Machida Y., Tamagawa H., Takimoto Y., Ueda M., Katayama T., Kawasaki S., Matsushita M., Seino T., Fukuhara S., Kanai T.

Nutrition (Nutrition) 74 2020.06

ISSN 08999007

Objectives: Early enteral nutrition is recommended for patients with severe acute pancreatitis (AP); however, nutritional management strategies for patients with mild AP have not been established. The aim of this study was to evaluate the benefits and safety of immediate oral intake of low-fat solid food in patients with mild AP who were allowed to take opioid analgesics. Methods: In this single-center randomized study, the immediate feeding (IMF) group was permitted immediate oral intake of low-fat (15 g/d) solid food. In the standard food (STF) group, patients received gradually increasing amounts of dietary fat. Twenty-six patients were randomized, with 13 allocated to each group. The primary outcome was the period between diagnosis and recovery from AP. The cost and rate of progression to severe disease were evaluated as secondary outcomes. Results: The IMF group (mean recovery days: 2 ± 1) recovered significantly earlier (mean difference in recovery days: 6.3; 95% confidence interval [CI], 4.8–7.9; P < 0.001) than the STF group (mean recovery days: 8.3 ± 2.3), with a lower overall treatment cost (mean difference in costs: −$460; 95% CI, −$880 to –$40; P = 0.034). The IMF group showed a lower rate of progression to severe AP (IMF, 0%; STF, 15.3%; P = 0.48). Conclusion: The initial treatment strategy for mild AP should be altered from the gradual introduction of oral feeding upon the absence of pain to immediate oral nutrition with opioid analgesics, to improve treatment efficacy and reduce treatment cost.

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

Yasuda H., Horibe M., Sanui M., Sasaki M., Suzuki N., Sawano H., Goto T., Ikeura T., Takeda T., Oda T., Ogura Y., Miyazaki D., Kitamura K., Chiba N., Ozaki T., Yamashita T., Koinuma T., Oshima T., Yamamoto T., Hirota M., Sato M., Miyamoto K., Mine T., Misumi T., Takeda Y., Iwasaki E., Kanai T., Mayumi T.

Pancreatology (Pancreatology) 20 ( 3 ) 307 - 317 2020.04

ISSN 14243903

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.

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

Iwasaki E., Minami K., Itoi T., Yamamoto K., Tsuji S., Sofuni A., Tsuchiya T., Tanaka R., Tonozuka R., Machida Y., Takimoto Y., Tamagawa H., Katayama T., Kawasaki S., Seino T., Horibe M., Fukuhara S., Kitago M., Ogata H., Kanai T.

Digestive Endoscopy (Digestive Endoscopy) 32 ( 1 ) 127 - 135 2020.01

ISSN 09155635

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).

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Large volume fluid resuscitation for severe acute pancreatitis is associated with reduced mortality: A multicenter retrospective study

Yamashita T., Horibe M., Sanui M., Sasaki M., Sawano H., Goto T., Ikeura T., Hamada T., Oda T., Yasuda H., Ogura Y., Miyazaki D., Hirose K., Kitamura K., Chiba N., Ozaki T., Koinuma T., Oshima T., Yamamoto T., Hirota M., Masuda Y., Tokuhira N., Kobayashi M., Saito S., Izai J., Lefor A.K., Iwasaki E., Kanai T., Mayumi T.

Journal of Clinical Gastroenterology (Journal of Clinical Gastroenterology) 53 ( 5 ) 385 - 391 2019.05

ISSN 01920790

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.

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Impact of Antimicrobial Prophylaxis for Severe Acute Pancreatitis on the Development of Invasive Candidiasis: A Large Retrospective Multicenter Cohort Study

Horibe M., Sanui M., Sasaki M., Honda H., Ogura Y., Namiki S., Sawano H., Goto T., Ikeura T., Takeda T., Oda T., Yasuda H., Miyazaki D., Hirose K., Kitamura K., Chiba N., Ozaki T., Yamashita T., Koinuma T., Oshima T., Yamamoto T., Hirota M., Yamamoto S., Oe K., Ito T., Masuda Y., Saito N., Iwasaki E., Kanai T., Mayumi T.

Pancreas (Pancreas) 48 ( 4 ) 537 - 543 2019.04

ISSN 08853177

Objective Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP. Methods This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis. Results Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029). Conclusions The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

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Electric endocut and autocut resection for endoscopic papillectomy: A systematic review

Minami K., Iwasaki E., Fukuhara S., Horibe M., Seino T., Kawasaki S., Katayama T., Takimoto Y., Tamagawa H., MacHida Y., Kanai T., Itoi T.

Internal Medicine (Internal Medicine) 58 ( 19 ) 2767 - 2772 2019

ISSN 09182918

Objective Risks of bleeding and pancreatitis after mucosal resection using the purecut/autocut and blendcut/ endocut modes for endoscopic papillectomy have not been fully clarified. Thus, a systematic review on electrosurgical cutting modes for endoscopic papillectomy was conducted focusing on the types and incidence of adverse events. Methods We searched the PubMed and Cochrane library for cases of endoscopic papillectomy recorded as of April 2017. Studies reporting the methods of electrically excising a tumor in the duodenal papilla and the number of adverse events were extracted. Studies were collected and examined separately based on the electrosurgical cutting mode, and the incidence rate for each adverse event was summarized. Results A total of 159 relevant articles were found; among them, 20 studies were included and 139 excluded. Five studies analyzed endoscopic papillectomy with the purecut/autocut mode and 16 with the blendcut/ endocut mode. Only one study investigated both modes (purecut and endocut). With the purecut/autocut mode, the incidence of bleeding was 2.8-50%, and that of pancreatitis was 0-50% (mean: 12.8%). With the blendcut/endocut mode, the incidence of bleeding was 0-42.3%, and that of pancreatitis was 0%-17.9% (mean: 9.5%). Conclusion Both methods had high adverse event rates for endoscopic papillectomy. Thus, a standard method of endoscopic papillectomy, including the electrosurgical cutting mode, needs to be established.

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Pancreatic Fat Content Detected by Computed Tomography and Its Significant Relationship with Intraductal Papillary Mucinous Neoplasm

Kashiwagi K., Seino T., Fukuhara S., Minami K., Horibe M., Iwasaki E., Takaishi H., Itoh K., Sugino Y., Inoue N., Iwao Y., Kanai T.

Pancreas (Pancreas) 47 ( 9 ) 1087 - 1092 2018.10

ISSN 08853177

Objectives Intraductal papillary mucinous neoplasms (IPMNs) are premalignant lesions of pancreatic ductal adenocarcinomas (PDACs). Fat accumulation in the pancreas is increasingly recognized as a cause of PDAC. We aimed to identify factors that are relevant between IPMN and metabolic-related factors, including pancreatic fat. Methods The database for 781 subjects who underwent a health checkup and upper abdominal magnetic resonance imaging was searched and computed tomography attenuation indexes (pancreatic and spleen attenuation, pancreas-to-spleen attenuation ratio) were decided by measuring the regions of interest in the pancreas and spleen on nonenhanced images, using Hounsfield units. Eighty-five subjects from each of the IPMN and noncyst groups were matched for age, sex, and glycemic status and statistically compared in clinical characteristics. Results There was no difference in metabolic-related factors except for apolipoprotein A1 and high-density lipoprotein cholesterol between the 2 groups in univariate analysis. Multivariate logistic regression analysis showed that both indexes were significantly associated with IPMN (odds ratio, 0.905 [95% confidence intervals, 0.851-0.963; P = 0.002]; odds ratio, 0.006 [95% confidence intervals, 0.000-0.152; P = 0.002]). Conclusions Pancreatic fat content measured by computed tomography was significantly associated with IPMN. These results suggest that IPMN may develop secondary to pancreatic steatosis that could be an overlapping risk factor for PDAC and IPMN.

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Absence of high-risk stigmata predicts good prognosis even in severely anemic patients with suspected acute upper gastrointestinal bleeding

Horibe M., Ogura Y., Matsuzaki J., Kaneko T., Yokota T., Okawa O., Nakatani Y., Iwasaki E., Nishizawa T., Hosoe N., Masaoka T., Yahagi N., Namiki S., Kanai T.

United European Gastroenterology Journal (United European Gastroenterology Journal) 6 ( 5 ) 684 - 690 2018.06

ISSN 20506406

Background: The need for a blood transfusion, defined as hemoglobin < 70 g/L, is the measure for assessing the risk levels in patients with upper gastrointestinal bleeding (UGIB). However, not all patients with a low hemoglobin level have a poor prognosis. Objective: We assessed the clinical predictive factors associated with poor short-term prognosis in patients with a low hemoglobin level. Methods: In this prospective cohort study, all consecutive patients with suspected acute UGIB at Tokyo Metropolitan Tama Medical Center were enrolled between 2008 and 2015. Then, we extracted those who needed a blood transfusion (hemoglobin < 70 g/L) and explored the variables associated with all-cause mortality within 28 days after presentation. Results: Among 1307 patients, 311 needed a blood transfusion and 13 (4.2%) died from all causes. The presence of high-risk stigmata requiring endoscopic treatment (peptic ulcers; Forrest scores Ia, Ib and IIa; varices with current bleeding or signs of recent bleeding; and spurting or gushing bleeding or visible vessel in other diseases), diagnosed by emergency endoscopy, was a unique factor affecting mortality (odds ratio: 8.47, 95% confidence interval: 1.45–160, P = 0.01). Patients without high-risk stigmata neither died from UGIB nor had rebleeding, irrespective of the hemoglobin levels. Conclusions: Patients without high-risk stigmata showed a good prognosis even if they needed a blood transfusion. This result could facilitate triage of patients with suspected acute UGIB who only need a blood transfusion.

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