Difference in the Types of Treated Cancer between Clinics and Small-to-Middle-Sized Hospitals in Rural Communities of Japan.

Resolution of regional disparities in cancer mortality is global challenge. Establishing an equal system of cancer treatment throughout the country is required under the Cancer Control Act in Japan. The types of treated cancer may reflect practical experience at the institutions and cooperation to other institutions. This study investigated the types treated at the institutions in rural communities of Japan. A questionnaire survey was conducted for 811 public rural institutions (clinics and small-to-middle-sized hospitals [< 200 beds]) in 2013. The survey's items included the types of treated cancer (14 categories: stomach, colon, breast, liver, biliary tract, pancreatic, prostate, esophageal, lung, renal, urinary tract, testicular, hematopoietic, and others) and the first five types were defined as major cancers. The data were analyzed between hospitals and clinics. The response rate was about 60%, and of 177 hospitals and 281 clinics, 54 hospitals (30%) and 10 clinics (3%) reported the types of cancer. The median number of cancer types in hospitals was significantly greater than that of clinics (4 [interquartile range 3.0-7.8]) vs. 1 [1.0-1.8], P < 0.01). The prevalence of hospitals treating at least one of five major cancers was significantly greater than that of clinics (96% vs. 30%, P < 0.01). The prevalence of clinics treating prostate cancer was significantly greater than that of hospitals (31% vs. 70%, P = 0.03). In conclusion, most types of cancer are treated at small-to-middle-sized hospitals, except for prostate cancer, providing basic information about cancer treatment in rural communities of Japan.

Total dosage of gardenia fruit used by patients with mesenteric phlebosclerosis.

BACKGROUND: Mesenteric phlebosclerosis (MP) is a disease characterized by fibrotic change or calcification of the mesenteric vein. Recently, there has been an increase in case reports of MP related to herbal medicine usage. Long-term intake of gardenia fruit (GF) is suspected as a possible cause. However, many GF users do not develop this disease and the association between GF and MP remains unclear. In this study, we investigated for the first time the dosage of GF used by patients with and without MP. METHODS: We used a medical chart review study design to assess the association between GF and MP. We reviewed patients with a history of intake of herbal medicines containing GF. Among these patients, we selected patients who were examined by colonoscopy and abdominal plain computed tomography (CT). We investigated the findings of colonoscopy, CT scan and histological examination. We assessed the total dosages of GF alongside the duration of ambulatory visit, the administration period of herbal medicine containing GF and pre-existing disease in order to compare MP cases and non-MP patients. RESULTS: Ten MP cases and 42 non-MP patients were analyzed. We summarized clinical findings of MP cases. All MP cases used more GF than non-MP patients and were administered more than approximately 5,000 grams of GF in cumulative dosage. CONCLUSIONS: This study indicated that excessive intake of GF contributes to and/or accelerates the development of MP suggesting that long-term usage of GF in excessive amounts increases the risk of MP.

Perilla leaf extract prevents atopic dermatitis induced by an extract of Dermatophagoides farinae in NC/Nga mice.

BACKGROUND: Perilla (Perilla frutescens Britton) leaf comprises many types of active components, mainly flavonoids, and acts as an anti-inflammatory agent in in vitro and in vivo atopic dermatitis (AD) models. OBJECTIVE: We investigated the effects of orally administered perilla leaf extract (PLE) on the symptoms of AD induced by Dermatophagoides farinae extract (DFE) in NC/Nga AD model mice. METHODS: The mice were allowed free intake of 0.5% PLE. Skin lesions were assessed, and blood was sampled from the caudal vein on days 0, 7, 14, 21, and 31. On day 31, all mice were sacrificed to obtain blood, skin, spleen, and intestinal tissue samples. RESULTS: The assessment scores of the skin lesions and total serum IgE levels of PLE-treated mice (PLE group) were significantly lower than DFE-treated mice (DFE group) on days 7, 14, and 21. On day 31, the serum periostin and thymus and activation-regulated chemokine (TARC) levels in the PLE group were significantly lower than those in the DFE group. Histological analysis of the skin revealed that hyperplasia of the epidermal and dermal layers and infiltration of inflammatory cells (cell infiltration in corium tissues) were suppressed by PLE. Periostin deposition was observed in the skin tissue obtained from the DFE group. Moreover, the CD4+/CD8+ ratio of splenic T cells was suppressed in the PLE group but not in the DFE group.

[Abnormal posture of the trunk related to donepezil hydrochloride: report of 2 cases].

Patient 1, an 80-year-old woman with Alzheimer's disease, had been taking donepezil 5 mg for 2 years. Donepezil was increased to 10 mg, and 2 months later, the patient developed dropped head syndrome. MRI and needle EMG abnormality of the neck extensor muscles suggested focal myopathy, but the symptom disappeared within 2 months by discontinuing donepezil. Patient 2, a 78-year-old man with Lewy body dementia, had been taking levodopa and pramipexole (PPX). One month after tapering levodopa, donepezil 3 mg was introduced, and Pisa syndrome (bending of the trunk to the right anterior direction) developed 10 days later. Donepezil and PPX were discontinued and levodopa was increased. Within 5 months, his posture had almost recovered. Cholinesterase inhibitors can induce abnormal posture of the trunk, and clinicians should be aware of this uncommon but important side effect.

Tracheoarterial fistula in a patient with amyotrophic lateral sclerosis successfully managed by overinflation of the tracheostomy tube cuff alone: a case report.

BACKGROUND: Tracheoarterial fistula is the most devastating complication after tracheostomy, and its mortality, without definitive treatment, approaches 100%. In general, the combination of bedside emergency management, that is, overinflation of the tracheostomy tube cuff, and definitive treatment such as surgical or endovascular intervention is necessary to prevent the poor outcome. Patients with neuromuscular diseases such as amyotrophic lateral sclerosis are susceptible to tracheoarterial fistula because of long-term mechanical ventilation and muscle weakness. CASE PRESENTATION: We describe a case of tracheoarterial fistula in a Japanese 39-year-old patient with amyotrophic lateral sclerosis with long-term ventilator management. The patient was clinically diagnosed with a tracheoarterial fistula because of massive bleeding following sentinel hemorrhage. The massive hemorrhage was controlled by overinflation of the tracheostomy tube cuff alone, without definitive treatment. CONCLUSIONS: This case suggests overinflation of the tracheostomy tube cuff alone plays an important role, semi-permanently, in the management of tracheoarterial fistula, especially in cases where surgical or endovascular intervention is not indicated. Clinicians taking care of patients with tracheostomy undergoing long-term mechanical ventilation should be aware that tracheoarterial fistula might occur following tracheostomy.

[Eosinophilic granulomatosis with polyangiitis presenting with ischemic optic neuropathy].

A 60-year-old man with a history of bronchial asthma and nasal polyp presented with loss of vision in the right eye. His visual loss progressed within a single day, and he presented to our hospital 5 days after the onset of the symptom. Fundoscopy showed swelling and hemorrhage of the right optic disc. Blood tests revealed increased eosinophils, C-reactive protein, and perinuclear anti-neutrophil cytoplasmic antibody. Cerebrospinal fluid was normal. Cranial MRI showed local enhancement of the right optic disc and posterior ciliary arteries. He was diagnosed with arteritic anterior ischemic optic neuropathy caused by eosinophilic granulomatosis with polyangiitis (EGPA). High dose intravenous methylprednisolone was started on presentation, but the patient showed no improvement in visual function. Although a rare complication, ischemic optic neuropathy associated with EGPA should be noted, as this is an emergent condition and requires prompt diagnosis and treatment.

Oral Administration of Mulberry (Morus alba L.) Leaf Powder Prevents the Development of Hepatocellular Carcinoma in Stelic Animal Model (STAM) Mice.

BACKGROUND/AIM: We examined the inhibitory effect of mulberry leaf (ML) (Morus alba L.) administration on the development of hepatocellular carcinoma (HCC) in stelic animal model (STAM) mice. This STAM mouse model of nonalcoholic steatohepatitis (NASH) closely resembles the progression from NASH to HCC in human clinical practice. MATERIALS AND METHODS: Streptozotocin (STZ, 200 µg) was administered to C57L/6J mice that were fed a high-fat diet (HFD; STAM mice) with 1% ML ad libitum. After sacrificing, the liver and blood were collected. Biochemical tests of plasma and histologic examination of the liver were performed. RESULTS: Pathologic examination of all (6/6) liver samples of the STAM mice showed HCC. On the contrary, in STAM mice that received ML, fat deposition and adenoma were observed in 6/6 and 2/6 of the liver samples, respectively, but there was no HCC. CONCLUSION: Administration of ML in STAM mice inhibited the progression from nonalcoholic hepatitis (NASH) to HCC. ML may be effective in preventing the development of HCC.

Detection of SARS-CoV-2 Genome for over 100 Days after COVID-19 Onset.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is spreading globally. Generally, the viral genome becomes undetectable within a couple of weeks after infection. Herein, we report a case of long-term detection of the SARS-CoV-2 genome in the same individual for 106 days. Whole genome sequencing was performed on specimens taken at the onset of the disease and 2 months after onset, and the B.1.1.7 lineage was detected in both samples. A comparison of the full-length sequences revealed a single-base difference and no amino acid mutations. This is the first case in Japan where the virus was detected over a long period, and the full-length sequences were compared.

Comparative effects of azelnidipine and amlodipine on myocardial function and mortality after ischemia/reperfusion in dogs.

Effects of azelnidipine were examined and compared with those of amlodipine on stunned myocardium in dogs. The left anterior descending (LAD) coronary artery was ligated for 20 min and subsequently released for 60 min. A vehicle, azelnidipine (0.3 mg/kg), or amlodipine (0.3 or 1 mg/kg) was injected intravenously 20 min before LAD ligation. The heart rate increased after a depressor response in the presence of amlodipine, while it decreased despite a decrease in arterial pressures in the presence of azelnidipine. After reperfusion, the coronary flow (CF) significantly increased in the presence of azelnidipine, but did not change with amlodipine after reperfusion. A positive inotropic effect was observed after treatment with both calcium antagonists. Ischemia significantly decreased the percentage of segment shortening (%SS) in all groups. Treatment with both calcium antagonists significantly increased %SS after reperfusion, although high-energy phosphate levels did not improve in the presence of calcium antagonists 60 min after reperfusion. Mortality with azelnidipine was significantly lower than that with 0.3 mg/kg amlodipine immediately after reperfusion. In conclusion, improvement in myocardial stunning after pretreatment with azelnidipine is associated with an increase in CF after reperfusion. The negative chronotropic action may have contributed to decreased mortality due to reperfusion arrhythmias. Azelnidipine is more beneficial than amlodipine and may provide an additional advantage to patients with angina and hypertension.

[A case of rectal mucosa-associated lymphoid tissue lymphoma (MALT) successfully treated by radiation therapy].

A 33-year-old woman had hematochezia for 5 months. A total colonoscopy showed an easily-bleeding elevated lesion with a nodular lesion in the lower rectum. Histological findings of a conventional biopsy from the lesion showed MALT (mucosa-associated lymphoid tissue) lymphoma and she was diagnosed as stage I. The monoclonality of B-cells was not detected by polymerase chain reaction products for immunoglobulin heavy chain. We selected antibiotic therapy because Helicobacter pylori was detected in culture of the patient's gastric biopsy specimens. The antibiotic therapy was successful, but her symptoms worsened. We therefore gave her with 30 Gy radiation therapy. She recovered a month after the radiation. Histological complete remission was confirmed 4 months after the radiation. Adverse events of the radiation therapy included anal pain for 1 month and premature ovarian failure. Radiation therapy may be useful for localized rectal MALT lymphoma.

Predictors of At-Home Death for Cancer Patients in Rural Clinics in Japan.

BACKGROUND: The prediction of at-home deaths has become an important topic in rural areas of Japan with an advanced aging society. However, there are no well-established predictors to explain how these factors influence intention. This study aims to investigate the possible predictors of at-home death for cancer patients in rural clinics in Japan. METHODS: This is a nationwide cross-sectional survey. A self-administered questionnaire was sent to 493 rural clinics in Japan. The main outcome was the realization of at-home deaths for cancer patients. RESULTS: Among the 264 clinics (54%) that responded to the survey, there were 194 clinics with the realization of at-home death. The use of a clinical pathway (adjusted odds ratio 4.19; 95% confidence interval 1.57-11.19) and the provision of organized palliative care (adjusted odds ratio 19.16; 95% confidence interval 7.56-48.52) were associated with the prediction of at-home death, irrespective of island geography or the number of doctors and nurses. CONCLUSIONS: Having a clinical pathway and systematizing palliative care could be important to determine the possibility of at-home deaths for cancer patients in rural clinics in Japan.

Effects of Kumaizasa (Sasa senanensis) Leaf Extract on Innate Immune Regulation in HEK293 Cells and Macrophages.

BACKGROUND/AIM: We investigated the effect of Kumaizasa leaf extract (KLE) on innate immunity using the HEK293 and RAW 264.7 cell lines. MATERIALS AND METHODS: KLE, lipopolysaccharides (LPS), or KLE with LPS were added to RAW 264.7 cells. The TNF-α and IL-1ß mRNA expression was then quantified. The expression of MAPKs, NFĸB, TNF-α and IL-1ß proteins was also quantified. In addition, KLE was added to HEK293 cells and the IL-8 concentration was measured. RESULTS: In RAW 264.7 cells, KLE increased the levels of TNF-α and IL-1ß mRNA. By contrast, when KLE and LPS were added to RAW 264.7 cells, the increase in TNF-α and IL-1ß mRNA was ameliorated. Similarly, the expression of JNK and ERK proteins was reduced. The addition of KLE to HEK293 cells induced IL-8 production. CONCLUSION: Based on these results, a KLE-mediated mechanism may regulate immunity by suppressing the expression of JNK and ERK, which are involved in inflammatory signal transduction.

Three major metabolites of mulberroside A in rat intestinal contents and feces.

Mulberroside A, a major stilbene constituent of MORUS ALBA L. (Moraceae), displays significant antitussive and antiasthmatic effects in animals. As part of our ongoing research on its biotransformation in rats, mulberroside A was orally administered to rats, and the metabolites in the gastrointestinal contents and feces were investigated. Three major metabolites were isolated from the feces of rats and identified as oxyresveratrol-2- O- beta- D-glucopyranoside ( 1), oxyresveratrol-3'- O- beta- D-glucopyranoside ( 2), and oxyresveratrol ( 3) on the basis of chemical and spectroscopic evidence. The three metabolites were also detected in the small intestinal contents of rats following oral administration of mulberroside A. These findings suggest that mulberroside A is metabolized prior to absorption into the body.

[A case of acute pancreatitis after extracorporeal shock wave lithotripsy for renal pelvic calculus].

A 62-year-old man was admitted to receive extracorporeal shock wave lithotripsy (ESWL) for a right renal pelvic calculus. During the operation, the patient complained of right upper quadrant pain. Later in the day, laboratory data showed elevated serum amylase levels, and abdominal CT revealed an enlarged pancreas. These findings led to a diagnosis of acute pancreatitis. The following day, urine output had decreased, and pleural and ascitic fluid had accumulated. For these reasons, the patient was transferred to our hospital to receive combination therapy, including arterial infusion therapy with protease inhibitors, antibiotics and continuous hemodiafiltration. The condition of the patient improved, and he was discharged on day 30. Acute pancreatitis should be considered as an early complication after ESWL for urinary tract calculus.

Acute Brainstem Dysfunction Caused by Cavernous Sinus Dural Arteriovenous Fistula.

Symptoms of cavernous sinus dural arteriovenous fistula depend on the drainage patterns and are very diverse. Among these, brainstem dysfunction is a rare but serious complication. Here, we describe a case with isolated and rapidly progressive brainstem dysfunction due to cavernous sinus dural arteriovenous fistula. An 80-year-old woman presented with a 2-day history of progressive gait disturbance. Neurological examination revealed mild confusion, dysarthria, and left hemiparesis. Magnetic resonance imaging (MRI) revealed pontine swelling without evidence of infarction. Magnetic resonance angiography suggested a faint abnormality near the cavernous sinus. Dural arteriovenous fistula was suspected, and digital subtraction angiography was planned for the next day. Her condition had progressed to coma by the next morning. Pontine swelling worsened, and hyperintensity appeared on diffusion-weighted imaging. Digital subtraction angiography revealed a right-sided cavernous sinus dural arteriovenous fistula with venous reflux into the posterior fossa. Orbital or ocular symptoms had preceded brainstem symptoms in all nine previously reported cases, but brainstem symptoms were the only presentation in our case, making the diagnosis difficult. Some dural arteriovenous fistulas mimic inflammatory diseases when the clinical course is acute. Prompt diagnosis using enhanced computed tomography or MRI and emergent treatment are needed to avoid permanent sequelae.

Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages.

Disturbed activation of autophagy is implicated in the pathogenesis of inflammatory bowel disease. Accordingly, several autophagy-related genes have been identified as Crohn's disease susceptibility genes. We screened the autophagy activators from a library including 3,922 natural extracts using a high-throughput assay system. The extracts identified as autophagy activators were administered to mice with 2% dextran sodium sulfate (DSS). Among the autophagy inducers, Sanguisorba officinalis L. (SO) suppressed DSS-induced colitis. To identify the mechanism by which SO ameliorates colitis, epithelial cell and innate myeloid cells-specific Atg7-deficient mice (Villin-cre; Atg7f/f and LysM-cre; Atg7f/f mice, respectively) were analyzed. SO-mediated inhibition of colitis was observed in Villin-cre; Atg7f/f mice. However, SO and a mixture of its components including catechin acid, ellagic acid, gallic acid, and ziyuglycoside II (Mix4) did not suppressed colitis in LysM-cre; Atg7f/f mice. In large intestinal macrophages (Mφ) of Atg7f/f mice, SO and Mix4 upregulated the expression of marker genes of anti-inflammatory Mφ including Arg1, Cd206, and Relma. However, these alterations were not induced in LysM-cre; Atg7f/f mice. These findings indicate that SO and its active components ameliorate DSS-induced colitis by providing intestinal Mφ with anti-inflammatory profiles via promotion of Atg7-dependent autophagy.

Clinical characteristics of autoimmune disorders in the central nervous system associated with myasthenia gravis.

Myasthenia gravis (MG) is occasionally associated with autoimmune diseases in the central nervous system (CNS), such as neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), Morvan syndrome, and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Here, we report five original cases associated with autoimmune disorders in the CNS among 42 patients with MG in a single tertiary hospital in Japan (11.9%). In four of these five cases, the second disease developed when the preceding disease was unstable. Accurate diagnosis of the newly developing disease may be difficult in such cases, because some neurological symptoms can be seen in both disorders. This implies the great importance of recognizing the possible co-occurrence of MG and disorders in the CNS. In addition, a comprehensive review of the literature revealed distinct clinical characteristics depending on the associated disease in the CNS, including thymic pathology and temporal relationship between MG and associated CNS disorders. Notably, NMOSD usually develops after the onset of MG and thymectomy, in clear contrast to MS. Thymoma is highly prevalent among patients with Morvan syndrome, in contract to cases with NMOSD and MS. The analysis of clinical characteristics, representing the first such investigation to the best of our knowledge, suggests different pathogeneses of these autoimmune diseases in the CNS, and provides significant implications for clinical practice.

Sudden-onset C8 Radiculopathy due to a Plexiform Schwannoma of the Cervical Nerve Root.

Plexiform schwannoma is a rare variant of schwannomas and usually presents with chronic symptoms. We herein report a case of cervical nerve plexiform schwannoma that presented with unusually sudden severe left radiculopathy of the eighth cervical nerve after physical exercise. Coronal short-tau inversion recovery (STIR) magnetic resonance imaging (MRI) revealed a multinodular tumor along the eighth cervical nerve. The tumor was partially resected. A pathological analysis revealed that the tumor was a schwannoma, and we diagnosed the case as a plexiform schwannoma. The unusual sudden-onset presentation in this case was considered to be caused by the unusual localization of the tumor involving the nerve root and mechanical stress due to physical exercise.

Hypertrophic Pachymeningitis in Sjögren's Syndrome.

Although central nervous system manifestations seem common in primary Sjögren's syndrome, hypertrophic pachymeningitis is rare. We herein describe a case of Sjögren's syndrome that was associated with hypertrophic pachymeningitis. Sjögren's syndrome should be considered as a cause of hypertrophic pachymeningitis.