Treatment outcomes of gemcitabine plus nab-paclitaxel in pancreatic cancer patients with malignant ascites.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) therapy has been shown to improve the prognosis in patients with metastatic pancreatic cancer (PC); however, the efficacy and safety of GnP in PC patients with malignant ascites (MA) remains unknown. METHODS: We retrospectively investigated PC patients with peritoneal dissemination who had received GnP as first-line chemotherapy at our institution between March 2015 and August 2021. The following patient data were reviewed: patient characteristics, overall survival (OS), progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and relative dose intensity (RDI). The severity of MA was categorized based on the CT findings as grade 1 (small), grade 2 (moderate), or grade 3 (massive). RESULTS: A total of 189 patients were included; the study endpoints were compared between patients with each ascites grade and 41 patients without MA. The MA was classified as grade 1 in 85 patients, grade 2 in 41 patients, and grade 3 in 22 patients. In the patients with MA, the median OS, PFS and ORR were 11.2 months, 5.7 months and 24.3%, respectively. The OS and PFS decreased with increasing the severity of MA; in particular, patients with grade 2 and 3 showed a poorer prognosis. There were no differences in AEs, except for anorexia, or the RDI according to the severity of MA. CONCLUSION: GnP showed moderate efficacy with manageable safety profile in PC patients with MA. However, PC patients with moderate to massive ascites still have a dismal prognosis, and further development of effective treatments is needed.

Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study.

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.

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.

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.

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.

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.

Usefulness of Adding Maspin Staining to p53 Staining for EUS-FNA Specimens of Pancreatic Ductal Adenocarcinoma.

Background: Endoscopic ultrasound-guided puncture aspiration biopsy (EUS-FNA) of pancreatic ductal adenocarcinoma (PDAC) is highly diagnostic, but it is difficult to distinguish from benign disease. Our objective was to determine the usefulness of maspin staining, in addition to conventional p53 staining, in the diagnosis of PDAC by EUS-FNA. Methods: Of the patients who underwent EUS-FNA and were diagnosed with PDAC, we retrospectively identified 90 cases in which both maspin and p53 staining were performed. In addition, we identified 28 cases of benign pancreatic disease diagnosed using EUS-FNA and these were selected as a control group. For analysis of EUS-FNA specimens, Cohen's Kappa (κ) coefficient and the prevalence and bias adjusted Kappa statistic (PABAK) were applied to assess the significance of sensitivity and specificity, comparing p53, maspin, p53+maspin. Results: The sensitivity and specificity of p53 staining were 48.9% and 100%. The κ coefficient was 0.31 (95%CI 0.18−0.44) (p < 0.01) and the PABAK coefficient was 0.22 (95%CI 0.03−0.40). The results for maspin staining were 88.9% and 92.9%. The κ coefficient was 0.72 (95%CI 0.54−0.90) (p < 0.01) and the PABAK coefficient was 0.78 (95%CI 0.64−0.88). The results for the combination of maspin and p53 staining were 94.4% and 92.2%. The κ coefficient was 0.82 (95%CI 0.64−1.00) (p < 0.01) and the PABAK coefficient was 0.86 (95%CI 0.74−0.94). Conclusion: Adding maspin staining to p53 staining showed high sensitivity and specificity. Our results demonstrated the usefulness of their combined use that might contribute to the improvement of tissue diagnostic performance of PDAC by EUS-FNA.

Curative resection with endoscopic submucosal dissection of early gastric cancer in Helicobacter pylori-negative Ménétrier's disease: A case report.

BACKGROUND: Adult-onset Ménétrier's disease is strongly associated with Helicobacter pylori (H. pylori) infection and an elevated risk of carcinogenesis. Cases of early-stage gastric cancer developed in H. pylori-negative Ménétrier's disease are extremely rare. We report a case of early gastric cancer in H. pylori-negative Ménétrier's disease that was curatively resected with endoscopic submucosal dissection (ESD). CASE SUMMARY: A 60-year-old woman was referred to our hospital after her medical examination detected anemia. Contrast-enhanced upper gastrointestinal (UGI) radiography revealed translucency of the nodule-aggregating surface with giant rugae. Blood tests showed hypoproteinemia and were negative for serum H. pylori immunoglobulin G antibodies. The 99mTc-DTPA-human serum albumin scintigraphy showed protein loss from the stomach. UGI endoscopy showed a 40-mm protruding erythematous lesion on giant rugae of the greater curvature of lower gastric body, suggesting early-stage gastric cancer due to Ménétrier's disease. En bloc resection with ESD was performed for diagnosis and treatment. Histology of ESD showed well-differentiated tubular adenocarcinoma. The cancer was confined to the mucosa, and complete curative resection was achieved. Foveolar hyperplasia and atrophy of the gastric glands were observed in non-tumor areas, histologically corresponding to Ménétrier's disease. Three years after ESD, gastric cancer had not recurred, and Ménétrier's disease remained in remission with spontaneous regression of giant gastric rugae. CONCLUSION: Complete curative resection was achieved through ESD in a patient with early-stage gastric cancer and H. pylori-negative Ménétrier's disease.

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.

Factors Affecting Technical Difficulty in Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography in Patients with Surgically Altered Anatomy.

Success rates of balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) for patients with a reconstructed intestinal tract after surgical procedures are unsatisfactory. We retrospectively investigated the factors associated with unsuccessful BE-ERCP. Ninety-one patients who had a reconstructed intestinal tract after gastrectomy or choledochojejunostomy were enrolled. Age, sex, operative method, malignancy, endoscope type, endoscopist's skill, emergency procedure, and time required to reach the papilla/anastomosis were examined. The primary endpoints were the factors associated with unsuccessful BE-ERCP selective cannulation, while the secondary endpoints were the rate of reaching the papilla/anastomosis, causes of failure to reach the papilla/anastomosis, cannulation success rate, procedure success rate, and rate of adverse events. Younger age (odds ratio, 0.832; 95% CI, 0.706-0.982; p = 0.001) and Roux-en-Y partial gastrectomy (odds ratio, 54.9; 95% CI, 1.09-2763; p = 0.045) were associated with unsuccessful BE- ERCP. The rate of reaching the papilla/anastomosis was 92.3%, the success rate of biliary duct cannulation was 90.5%, procedure success rate was 78.0%, and the rate of adverse events was 5.6%. In conclusion, Roux-en-Y partial gastrectomy and younger age were associated with unsuccessful BE-ERCP. If BE-ERCP is extremely difficult to perform in such patients after Roux-en-Y partial gastrectomy, alternative procedures should be considered early.

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.

Multiple esophageal ulcers due to tofacitinib 10 mg twice daily for ulcerative colitis.

A 26-year-old man was admitted to our institution for ulcerative colitis treatment. He used mesalamine, steroid, immunomodulators, and anti-TNFα anti-body, but it was difficult to maintain remission. We started induction therapy with tofacitinib (TOF) 10 mg twice daily. He maintained clinical remission but had chest pain 44 days after the start of TOF. Esophagogastroduodenoscopy showed multiple ulcers from middle to lower esophagus. Although rare, TOF induced esophageal ulcers were considered based on his clinical course and endoscopic findings.

Endoscopic score vs blood cell indices for determining timing of immunomodulator withdrawal in quiescent ulcerative colitis.

While immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p < 0.01). No significant difference was observed between the IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and the IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower (p = 0.08). Higher remission maintenance rates were observed in the IM continuation group of patients for whom MH had been achieved compared to the IM continuation group of patients for whom MH had not been achieved (p = 0.03). No significant difference was observed between the IM withdrawal group with MES 0 and the IM withdrawal group with MES 1. (p = 0.48). This retrospective study showed that remission maintenance could be firmly obtained by continuing IM administration in case of endoscopic MH; however, MH was not an indicator of IM withdrawal.

Relationship between endoscopic mucosal healing and histologic inflammation during remission maintenance phase in ulcerative colitis: a retrospective study.

Background and study aims Recently, histological inflammation has been suggested to be an important predictor of sustained remission or relapse of ulcerative colitis (UC). In this study, we retrospectively compared severity of histological inflammation with endoscopic findings in UC patients with mucosal healing (MH) in the remission maintenance phase, and investigated whether histological healing could be a predictor of sustained remission. Patients and methods This study included 166 patients with MH in the remission maintenance phase. Endoscopic evaluation was based on the Mayo endoscopic subscore (MES), and MH was defined as MES 0 or 1. Severity of histological inflammation was graded according to the Matts classification. Patients with Matts 1 and 2 were included in the histological healing (HH) group, and those with Matts 3, 4, and 5, in the non-histological healing (NHH) group. In patients with MH, incidence of relapse was compared and analyzed according to severity of histological inflammation. Results The remission maintenance rate was significantly higher in the MES 0 group than in the MES 1 group ( P  = 0.004). The rate was significantly higher in the HH group than in the NHH group ( P  = 0.003). Within the MES 1 group, the rate was significantly higher in the HH subgroup than in the NHH subgroup ( P  = 0.030). Conclusions This retrospective study suggests that histological healing can be a predictor of sustained remission in UC patients, and examination of histological inflammation provides useful information for long-term management of UC, particularly in patients with MES 1.

Severe acute pancreatitis with inflammation extending to the scrotum.

Extension of inflammation into the scrotum is rare in acute pancreatitis. If inflammation spreads in the scrotum, it may become severe. Clinicians should be aware of this condition as a possible complication. Proactive imaging testing is recommended when complaining of cyst swelling or testicular pain.

Gastroduodenal ulcer bleeding in elderly patients on low dose aspirin therapy.

AIM: To determine the clinical characteristics of elderly patients of hemorrhagic gastroduodenal ulcer on low-dose aspirin (LDA) therapy. METHODS: A total of 1105 patients with hemorrhagic gastroduodenal ulcer treated in our hospital between January 2000 and March 2016 were grouped by age and drugs used, and these groups were compared in several factors. These groups were compared in terms of length of hospital stay, presence/absence of hemoglobin (Hb) decrease, presence/absence of blood transfusion, Forrest I, percentage of Helicobacter pylori infection, presence/absence of underlying disease, and percentage of severe cases. RESULTS: The percentage of blood transfusion (62.6% vs 47.7 %, P < 0.001), Hb decrease (53.8% vs 40.8%, P < 0.001), and the length of hospital stay (23.5 d vs 16.7 d, P < 0.001) were significantly greater in those on drug therapy. The percentage of blood transfusion (65.3% vs 47.8%, P < 0.001), Hb decrease (54.2% vs 42.1%, P < 0.001), and length of hospital stay (23.3 d vs 17.5 d, P < 0.001) were significantly greater in the elderly. In comparison with the LDA monotherapy group, the percentage of severe cases was significantly higher in the LDA combination therapy group when elderly patients were concerned (16.1% vs 34.0%, P = 0.030). Meanwhile, among those on LDA monotherapy, there was no significant difference between elderly and non-elderly (16.1% vs 16.0%, P = 0.985). CONCLUSION: A combination of LDA with antithrombotic drugs or non-steroidal anti-inflammatory drugs (NSAIDs) contributes to aggravation. And advanced age is not an aggravating factor when LDA monotherapy is used.

Recent trends in the occurrence of bleeding gastric and duodenal ulcers under the Japanese evidence-based clinical practice guideline for peptic ulcer disease.

BACKGROUND: Gastrointestinal hemorrhage occurs frequently. We reviewed the tendency of occurrence of bleeding gastric and duodenal ulcers and their association with antithrombotic therapy before and after the widespread use of Evidence-Based Clinical Practice Guidelines for Peptic Ulcer 2009 (1st edition), which was published to improve treatment outcomes and prevent peptic ulcers. METHODS: The study enrolled 1105 patients with bleeding gastric and duodenal ulcers treated at our hospital between January 2000 and March 2016. They were divided into the preguideline group (807 patients treated between January 2000 and December 2010) and the postguideline group (298 patients treated between January 2011 and March 2016). The use of medications, severity, the incidence of Helicobacter pylori infection, the presence of any underlying disease, and other factors were compared between the pre- and postguideline groups. RESULTS: The number of patients receiving antithrombotic therapy was slightly higher in the postguideline group without a significant difference (P = 0.50). The incidence of H. pylori infection was significantly lower in the postguideline group (P < 0.001). The rate of premedication with a proton pump inhibitor (PPI) and the rate of severe ulcers were significantly higher in the postguideline group (P = 0.001 and P < 0.001, respectively). The rebleeding rate showed no significant difference, whereas the recurrence rate was significantly higher in the postguideline group (P = 0.041). CONCLUSIONS: The major cause of hemorrhagic gastroduodenal ulcers seems to be shifting from H. pylori infection to the administration of drugs with gastrointestinal risk. Antithrombotic therapy tends to be associated with severe ulcers but without statistical significance.