Measuring optimal ultrasound speed using endoscopic ultrasound in patients with chronic pancreatitis, including early stage.

OBJECTIVES: Ultrasound speed (USS) correction improves image quality by estimating the optimal USS correcting the deviation from a predetermined USS. This study assessed USS differences between chronic pancreatitis (CP), early CP (ECP), and normal pancreas when using endoscopic ultrasound (EUS). The usefulness of measuring optimal USS was evaluated for patients with CP, including early stage patients. METHODS: This study enrolled 116 consecutive patients for whom USS was measured using an EUS system. The USS correction principle is generation of a B-mode image by changing the USS in all ranges while correcting the delay in the received data. Final diagnoses were made according to the Japanese diagnostic criteria for CP in 2019. They were classified as CP, ECP, or normal. We compared USS applied for these three groups. RESULTS: The medians and ranges of USS values for patients in the normal, ECP, and CP groups were 1506.0 (1407-1600) m/s, 1580.0 (1520-1630) m/s, and 1574.0 (1537-1610) m/s, respectively. The USS values of the ECP and CP groups were significantly higher than those of the normal group (P < 0.001). Analyses of the receiver operating characteristic curve in the normal pancreas, ECP, and CP revealed the area as 0.957, with specificity and sensitivity of 95.9% and 87.5%, respectively, using the USS of 1535 m/s as a cut-off. CONCLUSION: Measurement of USS might be particularly useful for distinguishing between normal and ECP imaging.

Does the Use of Low Osmolality Contrast Medium Reduce the Frequency of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Comparative Study between Use of Low and High Osmolality Contrast Media.

INTRODUCTION: A few reports stating that differences in the various types of contrast media injected into the pancreatic duct are related to the onset of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) have been published, and it was indicated that iodixanol which is a nonionic iodide radiographic contrast medium with a dimeric (2 dimers) structure may reduce the incidence of PEP. The aim of this retrospective study is to evaluate the usefulness of iodaxanol for prevention PEP in comparison with megulamine amidototrizoate. METHODS: Two hundred and ninety-one patients were enrolled and divided into the 2 groups according to the contrast medium used. One hundred and fifty-five patients underwent ERCP with meglumine amidotrizoate, and 136 patients underwent ERCP with iodaxanol. The primary outcome of this study was the incidence of PEP associated with the use of each contrast medium. RESULTS: In this study, comparison of the meglumine amidotrizoate treatment and iodaxanol treatment groups showed no significant difference with respect to the incidence of PEP. In addition, there was also no difference between the groups with respect to PEP severity. CONCLUSION: Our study suggested that iodaxanol does not necessarily contribute to the prevention of PEP in comparison with meglumine amidotrizoate.

Crohn's Disease Activity Evaluation by Transabdominal Ultrasonography: Correlation with Double-Balloon Endoscopy.

OBJECTIVES: Transabdominal ultrasonography (US) has been reported as a useful tool for evaluating Crohn's disease (CD) activity. Endoscopic findings and Crohn's disease activity index (CDAI) are currently considered the gold standard for assessing CD activity. We assessed the correlation between US and double-balloon endoscopy (DBE), and CDAI for evaluating CD activity. METHODS: We analyzed patients with CD undergoing US and DBE within 10 days between the procedures. The intestine was divided into four segments and analyzed by the US scoring system (US-CD) and the simple endoscopic score for Crohn's disease (SES-CD). CDAI was compared with US-CD and SES-CD. Spearman's rank correlation coefficient was used for statistical analysis. RESULTS: Twenty-five patients with CD (11 women, 14 men; mean age 35.4 ± 14.9 years, range 16-65 years) were enrolled. Twenty-four patients received antitumor necrosis factor inhibitor therapy. CDAI was 128.1 (range 36-227). A significant moderate correlation was found between the US-CD and SES-CD in all segments (ρ = .64, P < .01). The US-CD showed a strong correlation with CDAI (ρ = .78, P < .01), whereas the SES-CD showed a moderate correlation (ρ = .55, P < .05). CONCLUSIONS: US-CD and SES-CD showed a moderate correlation for assessing CD activity. US-CD showed a stronger correlation with CDAI than SES-CD, suggesting that US could more accurately evaluate the disease activity.

Prevalence, clinical course, and predictive factors of immune checkpoint inhibitor monotherapy-associated hepatitis in Japan.

BACKGROUND AND AIM: Immune checkpoint inhibitors (ICI) have revolutionized anti-malignancy therapy and thus have been increasingly used. Although ICI may cause immune-related adverse events (irAE) in various organs, including the liver, the prevalence and predictive factors of irAE have not been clarified. METHODS: In this retrospective study, consecutive patients who had malignancies and were treated with ICI without other chemotherapeutic agents at Hokkaido University Hospital between 2014 and 2019 were screened. Patients were excluded if they were < 20 years old and had insufficient clinical data. RESULTS: Of the 233 patients screened, 202 patients met the inclusion criteria and were included in the analysis. The patients were aged 25-92 years, and 60.9% were male. The patients received nivolumab (n = 137), pembrolizumab (n = 45), ipilimumab (n = 17), atezolizumab (n = 2), and avelumab (n = 1). The prevalence of any grade and grade ≥ 3 irAE hepatitis was 8.4% (17/202) and 4.0% (8/202), respectively. irAE hepatitis occurred at a median duration of 42 days in any grade and 36 days in grade ≥ 3 after ICI initiation. The clinical course of grade ≥ 3 irAE hepatitis was generally favorable; however, 50% required corticosteroid treatment and two patients required additional mycophenolate mofetil. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis. CONCLUSIONS: Grade ≥ 3 irAE hepatitis was observed in 4.0% of the patients who were treated with ICI. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis.

A case report of a recurrent abscess secondary to fish bone penetration of the ileum.

A 62-year-old man with right upper abdominal swelling was admitted to our hospital. Abdominal computed tomography (CT) revealed a hepatic abscess. He was treated with percutaneous abscess drainage along with antibiotic therapy. After the treatment, the patient was discharged. However, we failed to notice a fish bone, which had been revealed in the CT scan. One year and five months later, the same patient presented with right lower abdominal pain and vomiting. Abdominal CT showed a subcutaneous abdominal abscess of the right lower abdomen, with the same fish bone penetrating out of the ileum. Accordingly, the patient was subjected to surgical abscess drainage, and the fish bone was successfully removed. The findings of this case suggest that the source of infection of the hepatic abscess should be identified, searching not only the nearby organs but also the distally located organs, including the lower gastrointestinal tract. The findings also suggest that the surgical removal of a fish bone should be considered.

A resected case of pancreatic head cancer developing 40 years after lateral pancreaticojejunostomy for chronic pancreatitis.

A 72-year-old male patient presented to our department complaining of with upper abdominal pain and jaundice. He had a history of a side-to-side pancreaticojejunostomy performed 40 years previously for chronic pancreatitis. A diagnostic workup revealed a tumor 3 cm in size in the pancreatic head as the etiology of the jaundice. Subsequently, the patient was diagnosed with resectable pancreatic cancer. Following two cycles of neoadjuvant chemotherapy, an extended pancreatoduodenectomy was performed because of tumor invasion at the previous pancreaticojejunostomy site. Concurrent portal vein resection and reconstruction were performed. Pathological examination confirmed invasive ductal carcinoma (T2N1M0, Stage IIB). This case highlights the clinical challenges in pancreatic head carcinoma following a side-to-side pancreaticojejunostomy. Although pancreaticojejunostomy is believed to reduce the risk of pancreatic cancer in patients with chronic pancreatitis, clinicians should be aware that, even after this surgery, there is still a chance of developing pancreatic cancer during long-term follow-up.

Characteristics and usefulness of transabdominal ultrasonography in immune-mediated colitis.

BACKGROUND/AIMS: The usefulness of ultrasonography (US) in diseases of the gastrointestinal tract has been reported recently. This prospective study aimed to determine the features of US findings in immune-mediated colitis (IMC), an adverse event induced by immune checkpoint inhibitor, and examine the correlation between US findings, colonoscopy (CS) findings, and severity of colitis. METHODS: We studied patients examined using CS and US upon suspicion of IMC in Hokkaido University Hospital between April 2018 and February 2021. Endoscopic findings of IMC were assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). The severity of US findings in IMC was evaluated using US grade, which is the ultrasonographic grading scale in ulcerative colitis. Bowel wall thickness and the intensity of the color Doppler signal were also analyzed. Severity of colitis was evaluated using Common Terminology Criteria for Adverse Events (CTCAE) grade version 5. RESULTS: Fourteen patients with IMC were enrolled. The US findings were bowel wall thickening, loss of stratification, ulceration and increased blood flow signal. The US grade was moderately correlated with the UCEIS (r=0.687, p=0.009) and CTCAE grade (r=0.628, p=0.035). Bowel wall thickness and UCEIS (r=0.628, p=0.020), as well as color Doppler signal grade and CTCAE grade (r=0.724, p=0.008), were significantly correlated. CONCLUSIONS: US findings in IMC were mainly similar to those of ulcerative colitis, but there were some findings that were characteristic only of IMC. Significant correlation was found between US findings, CS findings, and severity of colitis. Hence, US could be useful for the evaluation of IMC.

Proposal and Validation of New Diagnostic Criteria for Diagnostic Weights of Endoultrasonographic Findings for Early Chronic Pancreatitis.

[Background and study aim] A commonly applied method for diagnosing chronic pancreatitis (CP) uses endoscopic ultrasonography (EUS), assigning weights to each EUS diagnostic finding. It is the Rosemont classification (RC). In 2019, to improve EUS diagnostic specificity, Japanese diagnostic criteria for early chronic pancreatitis (ECP) were revised. Nevertheless, the criteria use no weighting of EUS diagnostic findings, as the RC does. This study was undertaken to propose diagnostic criteria that would weight each EUS finding of ECP and that would be more specific than the RC. [Methods] By EUS of the pancreas, 773 patients underwent detailed observation from January 2018 to March 2019 at our institution. An expert finalized all cases when patients were diagnosed. Using data from the medical records, 97 consecutive patients with EUS diagnostic findings of ECP based on the Japanese diagnostic criteria of ECP2009 (JDCECP2009) were selected. The definition under the RC of "Indeterminate for CP" was equivalent to ECP. Each case was diagnosed using (1) JDCECP2009 and (2) the Japanese diagnostic criteria of ECP2019 (JDCECP2019). Moreover, the four diagnostic EUS findings in JDCECP2019 were applied to the RC, weighted (modified-JDCECP2019), and subsequently compared with the earlier diagnostic criteria. As Modified-JDCECP2019, we suggested (3) RC-A-the current four items scored related to the RC, and (4) RC-B-the five items scored by dividing lobularity with and without honeycombing. [Results] Diagnoses produced based on each criterion were normal: ECP = (1) 20:77, (2) 46:51, (3) 52:42, and (4) 60:35. [Conclusions] Modified-JDCECP2019 may provide EUS diagnoses for ECP with higher specificity.

Diagnosing chronic pancreatitis by endoscopic ultrasound assessing the association between ultrasound and pathological findings: A narrative review.

Endoscopic ultrasound (EUS) is widely recognized for its non-invasiveness and for its usefulness in chronic pancreatitis (CP) diagnosis, including early CP. Although it is desirable to obtain a definitive diagnosis of CP by tissue sampling with EUS-guided fine needle aspiration, histopathological changes in CP are heterogeneous in terms of the extent and the distribution of lesions. Therefore, histopathological diagnosis of appropriate tissue sampling by EUS-fine needle aspiration is expected to be difficult. Furthermore, it is virtually impossible to match EUS images with pathological sections, making direct contrast between EUS findings and pathology difficult. This narrative review presents a discussion of the diagnosis of CP/early CP by EUS, particularly assessing the association between ultrasound and pathological findings. Recently, the histological corroboration and correlation of EUS findings related to CP have been clarified by surgical specimens, including those obtained from animal studies. Furthermore, remarkable advances have occurred in the objective and quantitative diagnosis of pancreatic fibrosis by EUS-elastography. Future technological advances in EUS are expected to improve the accuracy of diagnosis of pancreatic fibrosis at earlier stages.

A case in which the tip of a plastic stent placed to prevent recurrence of walled-off necrosis penetrated the bile duct and formed a stent-stone complex.

A woman in her 60s underwent endoscopic sphincterotomy for choledocholithiasis. Unfortunately, post-endoscopic retrograde cholangiopancreatography pancreatitis occurred. In addition, huge walled-off necrosis (WON) appeared as a late complication. For the infected WON, endoscopic ultrasound-guided fistuloplasty and endoscopic necrosectomy were performed, and a double pigtail plastic stent (PS) (7Fr, 7 cm) was placed to prevent a recurrence. Plain computed tomography conducted two years later showed that the stent implanted for WON had deviated. The distal end of the stent was found to have migrated into the bile duct. In addition, common bile duct stones with stents as nuclei were observed. Upon performing endoscopic retrograde cholangiography, it was revealed that the stent tip perforated the distal bile duct just above the papilla. After removal of the stent using grasping forceps, we made an incision between the duodenal - bile duct fistula and bile duct orifice using a sphincterotome. Then, the stone was removed by a balloon catheter. Although such late adverse events are rare occurrences, placement of long-term PS after treatment of WON should be followed up regularly with imaging examination, and if there is no recurrence for several months, removal of the PS at that point may be considered.

Investigating COVID-19 Pandemic Effects on Acute Pancreatitis Development-From the Perspective of Alcohol Sales (Consumption) in a Japanese Regional Hospital.

[Aim and Background] People's lifestyles changed considerably due to the coronavirus disease 2019 (COVID-19) pandemic. The number of patients with acute pancreatitis (AP) can be expected to decrease as alcohol consumption decreases. This study was conducted to assess COVID-19 pandemic effects on AP patients in a Japanese regional hospital. [Methods] Based on the first and second states of emergency declarations in Tochigi Prefecture, the survey periods were set as follows: period A, 16 April-14 May; period B, 15 May-13 January; period C, 14 January-7 February; and period D, 8 February-15 April. Using data acquired in 2017, 2018, 2019, and 2020, we retrospectively reviewed the number of patients admitted to our hospital with a diagnosis of AP, and their clinical characteristics. [Results] According to a National Tax Agency survey, the average alcohol sales per adult in Tochigi Prefecture were 71.3 L in 2017 before the pandemic, and 64.0 L in 2021 under the pandemic. The number of AP patients in 2020 was 38% lower than in 2017. Comparing 2017 with 2020, the number of alcoholic AP patients was lower in 2020 (p = 0.007). [Conclusions] The findings suggest that COVID-19-pandemic-related lifestyle changes contributed to the decrease in AP patients.

The Risk Factors for Progression to Chronic Pancreatitis in Patients with Past-History of Acute Pancreatitis: A Retrospective Analysis Based on Mechanistic Definition.

BACKGROUND: According to the mechanistic definition, the history of acute pancreatitis (AP) is a risk factor for chronic pancreatitis (CP). However, the etiology and severity of previous AP involved in the progression to CP have not been clarified. Here, we investigated risk factors for the progression to CP in patients with past-history of AP. METHODS: Sixty-four patients with AP who were followed-up for at least two years at our institution between April 2009 and March 2017 were enrolled. The multivariate analysis was performed based on the risk factors extracted by univariate analysis. RESULTS: Among the 64 patients, 13 patients (20.3%) progressed to CP (PCP group), while 48 did not (non-PCP group). Regarding the etiology of AP, rate of alcohol AP was significantly higher in the PCP group (76.9% vs. 33.3%, p = 0.003). In univariate analysis, smoking, number of previous AP, and alcohol consumption and drinking habits (Alcohol Use Disorders Identification Test-Concise; AUDIT-C) were identified as factors associated with progression to CP. Furthermore, multivariate analysis showed that AUDIT-C ≥ 6 points (male) and 4 points (female) after AP was a significant risk factor for CP (p = 0.003). CONCLUSIONS: Our results indicated that AUDIT-C ≥ 6 points (male) and 4 points (female) after AP was a risk factor in the process of progression to CP in patients with past-history of AP.

The Risk of Bleeding in Small/Straight Esophageal Varices with Red Color Sign on Endoscopy: A Retrospective Analysis from the Natural Course.

Red color sign-positive (RC-positive) esophageal varices present a high bleeding risk, necessitating prophylactic treatment. Among RC-positive esophageal varices, those classified morphologically as small straight varices (Form level 1: F1) are difficult to treat. Moreover, the appropriate time for therapeutic intervention remains undefined. This study assessed the bleeding risk in RC-positive F1 esophageal varices. After extracting 541 cases of F1 esophageal varices diagnosed during 1 January 2012−29 February 2020, 76 cases of RC-positive F1 esophageal varices were divided into two groups in terms of treatment intervention at diagnosis: 49 cases with (treatment group) and 27 cases without (follow-up group). We assessed the bleeding rates, bleeding-associated factors, and early-bleeding-associated factors. The treatment group's bleeding rate was 10% (5/49). The follow-up group's bleeding rate was 78% (21/24). The subsequent bleeding rate was low in the treatment group (p < 0.001). The median period of sustained absence of bleeding was longer in the treatment group than in the follow-up group (1156 [274−1582] days vs. 105 [1−336] days; p < 0.001). In the follow-up group, a significant number of bleedings had varices that included a hematocystic spot (HCS) as RC or combined with RC (p = 0.017). Early bleeding occurred often in varices that included HCS or combined with RC (p = 0.024). Red wale marking (RWM) only was not a factor of early bleeding (p = 0.012). In conclusion, RC-positive varices should be treated even as F1 varices. Patients with RWM only show the possibility of not accepting early treatment intervention. A fast response is crucially important in HCS cases because of its associated bleeding and early bleeding.

The impact of endoscopic sphincterotomy incision size on common bile duct stone recurrence: A propensity score matching analysis.

BACKGROUND/PURPOSE: The aim of this study is to clarify the relation between the incision size for endoscopic sphincterotomy (EST) and common bile duct stone (CBDS) recurrence. METHODS: Patients who underwent elective endoscopic treatment for CBDS between January 2013 and December 2017 were enrolled, excluding those who met the exclusion criteria. The clinical characteristics were investigated using propensity score matching analysis. RESULTS: A total of 243 patients were investigated. Propensity scores were calculated using multinomial logistic regression with five relevant variables (age, gender, follow-up time, maximum stone size, and bile duct diameter), which led to extraction of 188 cases to compose cohorts of the small and medium EST incision groups. The CBDS recurrence rate was 17.0% in the small incision group and 6.4% in the medium incision group. Multivariate analysis identified the medium incision as an independent predictor of CBDS recurrence (hazard ratio 0.350, 95% confidence interval 0.133-0.922, P = .034). The CBDS non-recurrence rate of the medium incision group was significantly higher than that of the small incision group (log-rank test P = .019). CONCLUSIONS: Our findings suggest that the CBDS recurrence rate was lower in EST with medium incision size than with small incision size.

Effectiveness of administering zinc acetate hydrate to patients with inflammatory bowel disease and zinc deficiency: a retrospective observational two-center study.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) patients frequently have zinc deficiency. IBD patients with zinc deficiency have higher risks of IBD-related hospitalization, complications, and requiring surgery. This study aimed to examine the effectiveness of zinc acetate hydrate (ZAH; Nobelzin) in IBD patients with zinc deficiency. METHODS: IBD patients with zinc deficiency who received ZAH from March 2017 to April 2020 were registered in this 2-center, retrospective, observational study. Changes in serum zinc levels and disease activity (Crohn's Disease Activity Index [CDAI]) before and after ZAH administration were analyzed. RESULTS: Fifty-one patients with Crohn's disease (CD, n = 40) or ulcerative colitis (UC, n = 11) were registered. Median serum zinc level and median CDAI scores significantly improved (55.5-91.0 µg/dL, P< 0.001; 171.5-129, P< 0.001, respectively) in CD patients 4 weeks after starting ZAH administration. Similarly, median serum zinc levels and CDAI scores significantly improved (57.0-81.0 µg/dL, P< 0.001; 177-148, P= 0.012, respectively) 20 weeks after starting ZAH administration. Similar investigations were conducted in groups where no treatment change, other than ZAH administration, was implemented; significant improvements were observed in both serum zinc level and CDAI scores. Median serum zinc levels in UC patients 4 weeks after starting ZAH administration significantly improved from 63.0 to 94.0 µg/dL (P= 0.002), but no significant changes in disease activity were observed. One patient experienced side effects of abdominal discomfort and nausea. CONCLUSIONS: ZAH administration is effective in improving zinc deficiency and may contribute to improving disease activity in IBD.