Primary esophageal mucosa‐associated lymphoid tissue lymphoma treated by endoscopic submucosal dissection

Primary esophageal mucosa‐associated lymphoid tissue (MALT) lymphoma is rare. There have been few reports about early primary esophageal MALT lymphoma being treated endoscopically. The clinical profile of primary esophageal MALT lymphoma is currently unclear, so it is important to accumulate more information about early esophageal MALT lymphoma. To achieve early detection of esophageal MALT lymphoma, we need more accurate knowledge and information about the macroscopic and morphological features of this tumor. Endoscopic resection is one of the most effective treatments. With respect to the lateral andvertical margins of the resected specimen, endoscopic submucosal dissection (ESD) may be superior to endoscopic mucosal resection for treating early esophageal MALT lymphoma. Here we report the macroscopic appearance of the tumor which is the first successful case of ESD for early esophageal MALT lymphoma.     

Heparin-induced thrombocytopenia with multiple organized thrombi accompanied by unusual cholesterin deposition: Autopsy case after long-term follow up

Heparin-induced thrombocytopenia (HIT) is characterized by a reduction in the platelet count and systemic thromboembolism during heparin therapy. Herein is reported a case of HIT with characteristic thrombus formation. A 68-year-old man who had been treated for hypertension for 27 years suffered a brain infarction and was treated with heparin. After this treatment, other new infarctions occurred in multiple organs. Because serum antibodies against heparin/PF4 complex were detected, he was diagnosed as having HIT, and warfarin and argatroban were administered instead of heparin. He died, however, 119 days after the first onset. At autopsy infarction due to organized thrombi with cholesterin deposition in multiple organs were found, similar to usual atherosclerotic emboli, but different to them with regard to clinical course and distribution of thrombi. This case in which organization and frequent cholesterin deposition were found in thromboembolized lesions of multiple organs after relatively long-term follow up, is unusual. The findings suggest that HIT accompanied by marked hypercholesterolemia of long duration contributes to a characteristic form of thromboembolism that needs careful management.     

Probiotic-Derived Polyphosphate Prevents Pancreatitis

Digestive Diseases and Sciences -     

A Targeted Biopsy during Menstruation for the Definitive Diagnosis of Rectovaginal Endometriosis: A Report of Two Cases

We herein report the definitive diagnosis of rectovaginal endometriosis in two cases. Case 1 involved a 46-year-old woman with abdominal pain and hematochezia. The diagnosis after the first and second examinations using lower gastrointestinal (GI) endoscopy was unclear. Differential diagnoses included mucosa-associated lymphoid tissue and colorectal cancer. The third lower GI endoscopy with a targeted biopsy, performed during menstruation, confirmed rectovaginal endometriosis. Case 2 involved a 38-year-old woman with hematochezia. Lower GI endoscopy during menstruation revealed rectovaginal endometriosis. When rectovaginal or bowel endometriosis is suspected, lower GI endoscopy and a targeted biopsy during menstruation can prevent unnecessary surgery.     

Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Solitary organ autoimmune disorders, formerly known as autoimmune pancreatitis (AIP), autoimmune sialadenitis, and autoimmune sclerosing cholangitis, are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease (IgG4-RD). AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody (Ab), accumulation of IgG4-expressing plasmacytes in the affected organs, and involvement of multiple organs. It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity. However, a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype. In addition, disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone. Therefore, it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD. Recently, we found that activation of plasmacytoid dendritic cells producing both interferon-α (IFN-α) and interleukin-33 (IL-33) mediate murine AIP and human IgG4-RD. More importantly, we provided evidence that serum concentrations of IFN-α and IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders. In this Frontier article, we have summarized and discussed biomarkers of AIP and IgG4-RD, including Igs, autoAbs, and cytokines to provide useful information not only for clinicians but also for researchers.     

Analysis of nocturnal desaturation waveforms using algorithms in patients with idiopathic pulmonary fibrosis

Purpose

Sleep-disordered breathing is recognized as a comorbidity in patients with idiopathic pulmonary fibrosis (IPF). Among them, nocturnal hypoxemia has been reported to be associated with poor prognosis and disease progression. We developed a diagnostic algorithm to classify nocturnal desaturation from percutaneous oxygen saturation (SpO₂) waveform patterns: sustained pattern, periodic pattern, and intermittent pattern. We then investigated the prevalence of nocturnal desaturation and the association between the waveform patterns of nocturnal desaturation and clinical findings of patients with IPF.

Methods

We prospectively enrolled patients with IPF from seven general hospitals between April 2017 and March 2020 and measured nocturnal SpO₂ and nasal airflow by using a home sleep apnea test. An algorithm was used to classify the types of nocturnal desaturation. We evaluated the association between sleep or clinical parameters and each waveform pattern of nocturnal desaturation.

Results

Among 60 patients (47 men) who met the eligibility criteria, there were 3 cases with the sustained pattern, 49 cases with the periodic pattern, and 41 cases with the intermittent pattern. Lowest SpO₂ during sleep and total sleep time spent with SpO₂?<?90% were associated with the sustained pattern, and apnea–hypopnea index was associated with the intermittent pattern.

Conclusion

We demonstrated the prevalence of each waveform and association between each waveform and sleep parameters in patients with IPF. This classification algorithm may be useful to predict the degree of hypoxemia or the complication of obstructive sleep apnea.

     

An optimal therapeutic expression level is crucial for suicide gene therapy for hepatic metastatic cancer in mice

The most serious problem in current gene therapy is discrepancies between experimental data and actual clinical outcomes, which may be due to insufficient analyses and/or inappropriate animal models. We have explored suicide gene therapy by using various clinically relevant animal models and doubt the clinical use of maximal suicide gene expression, which has been generally recommended. To explore this subject further, we studied what expression level of suicide gene and what promoter led to the maximal clinical benefit in the case of hepatic metastatic cancer in mice. Therapeutic and adverse side effects of 4 adenoviral vectors that express herpes simplex virus thymidine kinase (HSV-tk) under different promoters were scrupulously investigated in 2 mouse models of hepatic metastasis of gastric cancer that possess clinical characteristics. Surprisingly, increases in HSV-tk expression beyond a certain point, achieved by the Rous sarcoma virus long terminal repeat promoter, not only enhanced the adverse side effects of lethal hepatotoxicity and ganciclovir-independent cytotoxicity but also failed to further increase therapeutic potential. Moreover, the carcinoembryonic antigen (CEA) tumor-specific promoter, the therapeutic potential of which had been underestimated, was much more useful-even in the case of low CEA-producing cancer-than had been previously reported. In conclusion, the optimal therapeutic expression level of a suicide gene is a novel concept and a crucial factor for successful cancer gene therapy. The present results, which contradict those of previous studies, alert researchers about possible problems with ongoing and future clinical trials that lack this concept.     

Regulation of estrogen receptor alpha and beta expression by testosterone in the rat prostate gland

Although ER beta is known to be expressed at high levels in the rat prostate gland, its regulation is not well understood. Here we examined ER mRNA expression and the effects of testosterone administration in male rats at 1, 4 and 9 weeks of age who were castrated and/or treated with testosterone for a week, and then sacrificed. ER alpha was the major type of ER expressed in 2 week-old animals while dominant expression of ER beta mRNA was apparent in older age groups. Interestingly while ER beta expression was diminished and ER alpha mRNA increased in the castrated group, testosterone administration reversed this effect. A time-course study indicated that induction of ER beta mRNA increased within 9 hr and ER alpha decreased in 2 days after an injection (i.p.) of testosterone. Our results suggested that 1) testosterone up-regulates ER beta mRNA expression while ER alpha is down-regulated; and that 2) great changes in ER alpha and beta expression in the prostate gland during development from the newborn to adult may be due to the influence of testosterone.