A case of acute recurrent pancreatitis caused by biliopancreatic reflux without pancreaticobiliary maljunction.

Acute recurrent pancreatitis (ARP) is a clinical condition characterized by repeated episodes of acute pancreatitis. In this case study, a 62-year-old man was diagnosed with mild pancreatitis five years ago, with alcohol intake initially considered the cause. Since then, he experienced three episodes of pancreatitis despite ceasing alcohol consumption completely. Consequently, the patient was diagnosed with ARP. Various diagnostic and imaging tests were performed to determine the etiology of his condition, including blood tests, magnetic resonance cholangiopancreatography, endoscopic ultrasonography, and contrast-enhanced computed tomography. The results were inconclusive; however, endoscopic retrograde cholangiopancreatography revealed the reflux of bile and pancreatic juice into the alternative ducts, despite the absence of anatomical abnormalities in the biliary tract or pancreatic duct. These findings subsequently led to the diagnosis of biliopancreatic reflux, which activated pancreatic enzymes causing ARP. Endoscopic biliary sphincterotomy was performed to alleviate the patient's symptoms. One year later, the patient remained symptom-free. This case highlights the importance of examining bile and pancreatic juice components before considering endoscopic sphincterotomy in patients with unexplained ARP.

Endoscopic diagnosis of chronic diarrhea.

The prevalence of chronic diarrhea in the general population is reported to be 4%-5%. Since various pathological conditions cause diarrheal symptoms, etiological diagnosis of chronic diarrhea is difficult in many cases. Medical history taking, physical examinations, and laboratory testing are not adequately sensitive or specific, thus a colonoscopic investigation is frequently employed for etiological evaluation. However, for cases with non-bloody chronic diarrhea, the diagnostic yield of a colonoscopy procedure is reported to be not high enough. Furthermore, endoscopically identifiable findings are not adequately specific for the diagnosis of diarrheal disease, except for inflammatory bowel disease, while microscopic colitis, amyloidosis, eosinophilic gastroenteritis, celiac disease, and bile acid diarrhea are difficult to definitively diagnose using endoscopic findings. Thus, a histopathological examination of biopsy samples obtained with endoscopy is critically important. Endoscopists should consider obtaining biopsy samples from even normal-appearing gastrointestinal mucosa for chronic diarrhea diagnosis.

A case of COVID-19 diarrhea relieved by bile acid sequestrant administration.

Patients with coronavirus disease 2019 exhibit various gastrointestinal symptoms. Although diarrhea is reported in many cases, the pathophysiology of diarrhea has not been fully clarified. Herein, we report a case of coronavirus disease 2019 with diarrhea that was successfully relieved by the administration of a bile acid sequestrant. The patient was a 59-year-old man whose pneumonia was treated by the administration of glucocorticoids and mechanical ventilation. However, beginning on the 30th hospital day, he developed severe watery diarrhea (up to 10 times a day). Colonoscopy detected ulcers in the terminal ileum and ascending colon. The oral administration of a bile acid sequestrant, colestimide, improved his diarrhea quickly. Ileal inflammation is reported to suppress expression of the gut epithelial apical sodium-dependent bile acid transporter. It decreases bile acid absorption at the distal ileum and increases colonic delivery of bile acids, resulting in bile acid diarrhea. In summary, the clinical course of the case presented in this report suggests that bile acid diarrhea is a possible mechanism of watery diarrhea observed in patients with coronavirus disease 2019.

Folinic Acid, Fluorouracil, and Oxaliplatin Therapy for Recurrent Esophageal Cancer with Syndrome of Inadequate Antidiuretic Hormone Secretion (SIADH) After Preoperative Cisplatin/5-Fluorouracil Therapy.

BACKGROUND Cisplatin/5-fluorouracil therapy is the standard therapy for unresectable and recurrent esophageal cancer. Cisplatin-based chemotherapy often causes adverse effects, such as nausea, vomiting, and renal dysfunction, which may necessitate dose modification or treatment prolongation. Therefore, novel combination therapies are urgently needed to improve the efficacy and overcome drug toxicity in this setting. CASE REPORT A 77-year-old man with advanced esophageal cancer received cisplatin/5-fluorouracil therapy as neoadjuvant chemotherapy. On day 8 of administration, the patient had lightheadedness, diaphoresis, and nausea and became unconscious and developed severe hyponatremia. We diagnosed the patient with cisplatin-induced syndrome of inadequate antidiuretic hormone secretion (SIADH). Subsequently, water restriction was started, and treatment with a salt-added diet and 3% hypertonic saline infusion was initiated. The hyponatremia improved and the patient was discharged on day 16 of administration. Therefore, neoadjuvant chemotherapy was discontinued, and surgical treatment was performed. However, the tumor recurred and chemotherapy was required. The patient developed severe hyponatremia while receiving neoadjuvant chemotherapy; hence, folinic acid, fluorouracil, and oxaliplatin therapy (FOLFOX) were administered as an alternative treatment. The patient completed the FOLFOX therapy without developing SIADH. CONCLUSIONS The cisplatin/5-fluorouracil therapy is currently the standard chemotherapy regimen for esophageal cancer. However, SIADH is a known adverse effect when using cisplatin. In patients with esophageal cancer, oxaliplatin appears to have a lower risk of SIADH than cisplatin, suggesting that oxaliplatin can be a therapeutic option for patients with esophageal cancer who are at high risk of SIADH.

[An autopsy case of anaplastic pancreatic carcinoma with diffuse liver metastases in acute hepatic failure].

A 76-year-old man presented to our hospital with continuous abdominal pain and vomiting. The results of the computed tomography indicated a pancreatic head mass with multiple liver metastatic tumors. Multiple liver tumors progressed rapidly, and the patient died of the resulting acute hepatic failure approximately 1 month after the onset of symptoms. The results of the postmortem examination indicated anaplastic pancreatic carcinoma (pleomorphic type) with multiple liver metastases. The tumor cells in the primary pancreatic lesion and liver metastases were replaced with normal tissue, and they showed a decrease in stainability by E-cadherin staining. Overall, the pathological findings suggested that the inhibition of E-cadherin may be related to the proliferation and infiltration of anaplastic cancer cells.

Successful Treatment of Bouveret Syndrome by Electrohydraulic Lithotripsy and Double Balloon Endoscopy.

BACKGROUND Bouveret syndrome is a rare complication of cholelithiasis that often leads to symptoms of gastric outlet obstruction. CASE REPORT An 84-year-old woman developed acute abdominal symptoms due to impaction of a gallstone in the horizontal part of the duodenum. The diagnosis was supported by abdominal computed tomography and double balloon endoscopy. Considering her advanced age and the position of the calcified gallstone, we decided to perform electrohydraulic lithotripsy using double balloon endoscopy for treatment. Finally, the impacted stone was removed with reduced size. She was discharged home 10 days after admission without recurrence. CONCLUSIONS This case illustrates that electrohydraulic lithotripsy using double balloon endoscopy is very effective, especially for treatment of Bouveret syndrome caused by gallstone impaction in the horizontal part of the duodenum.

Long-term follow up of peginterferon-α-2a treatment of hepatitis B e-antigen (HBeAg) positive and HBeAg negative chronic hepatitis B patients in phase II and III studies.

AIM: We analyzed the 5-year post-treatment response to peginterferon α-2a (PEG IFN-α-2a) in hepatitis B e-antigen (HBeAg) positive and negative chronic hepatitis B patients. METHODS: One hundred and thirty-seven chronic hepatitis B (CHB) patients receiving 90 µg or 180 µg of PEG IFN-α-2a for 24 or 48 weeks in phase II or III studies were enrolled in the study, including 100 HBeAg positive patients and 37 HBeAg negative patients; 121 patients (88.4%) had genotype C. RESULTS: Of the 137 patients, 94 received additional antiviral therapy because of viral reactivation and 43 did not receive any additional antiviral treatment during follow up. Five years upon PEG IFN-α-2a treatment, 32 patients (23.4%) who did not receive any additional antiviral agent after PEG IFN-α-2a therapy achieved a good response (normal serum alanine aminotransferase, low-level hepatitis B virus [HBV] DNA, and HBeAg negativity). Female sex and low HBV DNA levels by the end of treatment were independently associated with favorable 5-year post-treatment responses. Forty-eight-week administration of PEG IFN-α-2a showed a better response (26.4%) than 24-week administration (18.0%). Six patients (4.3%), four males and two females, cleared hepatitis B surface antigen (HBsAg) during the 5-year follow-up period. CONCLUSION: The 48-week administration of PEG IFN-α-2a achieved better biochemical and virological responses than the 24-week administration, particularly in younger females. The 5-year post-treatment response rate was 23.4%; however, more than two-thirds of the patients received additional antiviral therapy because of viral reactivation after PEG IFN-α-2a treatment. HBsAg clearance was noted in six patients (4.3%). PEG IFN-α-2a is effective in young female patients.

Double-Filtration Plasmapheresis plus Interferon-ß for HCV-1b Patients with Non-Sustained Virological Response to Previous Combination Therapy.

BACKGROUND AND AIMS: Double-filtration plasmapheresis (DFPP) together with interferon (IFN) administration produces a substantial reduction in the viral load during the early stages of treatment. METHODS: Based on their responses to previous pegylated IFN and ribavirin (PEG-IFN/RBV) therapy, 20 patients were divided into null virological response (NVR; n = 12) and relapse (n = 8) groups. DFPP was used in combination with IFN-ß/RBV with subsequent administration of PEG-IFN-α2a/RBV therapy (DFPP + IFN-ß/RBV then PEG-IFN/RBV). Early viral dynamics was assessed, focusing especially on complete early virological response (cEVR) associated with sustained virological response. Additionally, the interleukin 28B gene, the IFN/RBV resistance-determining region, the IFN sensitivity-determining region and the core regions were analyzed. RESULTS: Rapid virological response was achieved in 0% (0/12) of NVR and in 75% (6/8) of relapse patients, with a significant difference between the two groups (p = 0.001). Similarly, cEVR was achieved in 8% (1/12) of NVR and in 88% (7/8) of relapse patients, with a significant difference between the two groups (p = 0.037). By multivariate logistic regression analysis, interleukin-28B major was a significant determiner of cEVR (odds ratio = 24.19, p = 0.037). CONCLUSION: DFPP + IFN-ß/RBV then PEG-IFN/RBV therapy is indicated more for relapse than for NVR patients.

In vivo interferon system assessed by 2'-5' oligoadenylate synthetase activity in chronic hepatitis C virus patients treated with pegylated interferon and ribavirin.

AIM: 2',5' oligoadenylate synthetase (2-5AS), an enzyme induced by interferon, is an accurate indicator of the antiviral effect of interferon. We measured it during pegylated interferon based therapies in patients with chronic hepatitis C virus (HCV) in order to determine the dynamics of antiviral status in vivo and the relationship between the response to exogenous interferon and the outcome of therapy. METHODS: A total of 160 patients with chronic HCV were treated with pegylated interferon alfa 2a or 2b or non-pegylated interferon, with or without ribavirin. Serum 2-5AS activity was measured by radioimmunoassay assay kits every 2 weeks. RESULTS: In 60 patients treated with pegylated interferon alfa 2a or 2b, 2-5AS levels increased to 7-40 times (average 235 pmol/dL) above the pretreatment levels (30 pmol/dL), which were significantly higher than the levels during non-pegylated interferon therapy. Ribavirin did not enhance 2-5AS levels. 2-5AS levels between sustained virological response (SVR) and non-SVR, including null responders to pegylated interferon plus ribavirin therapy were not significantly different. CONCLUSION: 2-5AS levels were significantly higher in patients treated with pegylated interferon than in those treated with non-pegylated interferon, suggesting that pegylated interferon is more potent at inducing interferon response genes resulting in an improved antiviral effect. Ribavirin did not appear to be related to interferon response gene induction.

Early reduction of infected hepatocytes by activated immunity at the time of interferon withdrawal hepatitis followed by lamivudine administration resulted in higher seroconversion in hepatitis Be antigen-positive patients with chronic hepatitis B.

BACKGROUND: It has been found that the efficacy of lamivudine (LAM) therapy can be improved by preceding administration with a short course of corticosteroid that induces a flare of the disease upon its withdrawal. Because of the side effects of corticosteroid, we tested the effect of a short course of interferon (IFN) as the primer instead of prednisolone, which was followed by LAM when the hepatitis flare occurred. The incidence of LAM resistance mutations and the effect of core promoter and precore mutations on the durability of the responses were also studied. METHODS: Patients treated with interferon (IFN)-LAM therapy (n=73) were compared to those treated with IFN alone (n=117). The IFN-LAM group received IFN-alpha MU/day, t.i.w. for a 3-month period. LAM (10mg/day during 1 year) was started when IFN withdrawal hepatitis occurred during 2-10 months after stopping IFN. The LAM-resistant, core promoter, and precore mutations were examined by sequencing. RESULTS: (1) The IFN-LAM group developed exacerbated hepatitis following IFN withdrawal in 63 patients before starting LAM therapy. The seroconversion (SC) rate was significantly higher in the IFN-LAM group than in the IFN-alone group (61% vs 26%, P=0.0001). (2) The LAM resistance mutation rate was 31% at 1 year after initiating LAM therapy. (3) In a stepwise discriminant-function analysis, decreased level of HBeAg determined at 4 weeks after LAM administration and increased level of HBeAb before the start of LAM administration contributed significantly on seroconversion to anti-HBe (P = 0.0073 and 0.004, respectively). (4) The reappearance rate of HBeAg within 6 months after the therapy (relapse) was 33% in the IFN-LAM group and 10% in the IFN-alone group. The prevalence of core promoter and precore mutations did not change before and after the therapy, nor did these mutations correlate with the relapse after stopping IFN-LAM therapy. CONCLUSIONS: (1) Our findings suggest that early reduction of infected hepatocytes expressed by HBeAg by LAM may contribute to a high SC rate of IFN-LAM therapy. (2) The emergence of LAM-resistant mutations was similar to the previously reported rate, and neither core promoter nor precore mutations correlated with relapse of seroconverters after IFN-LAM withdrawal.

Macroscopic and microscopic findings of livers in malignant hematologic disorders, biopsied under peritoneoscopy.

It is important to detect liver involvement in extranodal lesions in malignant hematologic disorders to make accurate diagnoses and estimate their clinical stage. We report seven cases of malignant lymphoma and a case of histiocytosis X. All patients expressed positive C-reactive protein and a high erythrocyte sedimentation rate, and a high serum value of alkaline phosphatase or lactic dehydrogenase was seen. Image analyses revealed enlarged livers without any space-occupying lesions. Peritoneoscopy with liver biopsy showed a diffuse presence of white maculae or peliosis hepatis on the liver surface among all the patients, and granulomas with or without malignant cells were observed histologically and congestion was seen in the lobules. Thus, peritoneoscopy with liver biopsy appears to be a useful tool not only to detect early liver involvement in malignant hematologic disorders but also to make their accurate diagnosis.

Influence of transfection with connexin 26 gene on malignant potential of human hepatoma cells.

We investigated the effect of transfection with connexin (Cx) 26 gene on the malignant potential of PLC/PRF/5 hepatoma cells, observing changes in their morphological features, alpha-fetoprotein (AFP) expression, cell proliferation and apoptosis in vitro, and their tumor growth in vivo. Fluorescence-activated cell sorting (FACS) analysis showed that 10.6% of PLC/PRF/5 hepatoma cells transfected with Cx26 cDNA expressed excessive Cx26, and the spread of lucifer yellow was wider in the colony of stable transfectants (PLC/Cx26) after its microinjection than in control. Nucleo-cytoplasmic (N/C) ratio was significantly lower in PLC/Cx26 (P < 0.0001). Cell proliferation assay showed significantly lower numbers in PLC/Cx26 on day 10 after seeding than in control (P = 0.0039), and AFP level /10(5) cells was significantly lower in medium of PLC/Cx26 (P = 0.0039). The number of proliferating cell nuclear antigen (PCNA)-positive cells was less in PLC/Cx26 in vitro than in control (P = 0.0039), and single-stranded DNA (ssDNA)-positive cells were more abundant in the colony of PLC/Cx26 (P = 0.029). Tumor volume in SCID mice was significantly smaller in the group of PLC/Cx26 than in the control (P < 0.01) throughout the observation period, and tumor weight of PLC/Cx26 was significantly lower (P = 0.0019) week 9 after inoculation. Transfection with Cx26 cDNA inhibited dedifferentiation, suppressed cell proliferation, and apoptosis was induced. Tumor growth of PLC/Cx26 was retarded. These findings suggest that transfection with Cx26 gene into human hepatoma cells reduces their malignant potential.