We herein report a very rare case of spontaneous regression of recurrent undifferentiated carcinoma of the endometrium. An 80-year-old woman had undergone total hysterectomy with bilateral adnexectomy for undifferentiated carcinoma of the endometrium. The cancer recurred locally 10 months after surgery and then metastasized to the lung and liver. After she and her family elected to receive supportive care without active treatment, the local recurrences dramatically decreased, and the metastases of the lung, liver, and peritoneum also disappeared. This case showed that spontaneous regression can occur even with malignant tumors showing an extremely poor prognosis, such as undifferentiated carcinoma of the endometrium.

Background Extracorporeal life support (ECLS) is effective for improving the survival rate of patients with refractory cardiac arrest (rCA). As little data are available regarding the impact of ECLS on a favorable neurological outcome, the predictors of a favorable neurological outcome were evaluated in this study.

Methods Between January 2007 and August 2016, we retrospectively recruited patients with rCA caused by cardiac events treated with ECLS in our institute. A favorable neurological outcome was defined as a Glasgow-Pittsburgh cerebral performance category score 1 at discharge. The study endpoint was the clinical outcomes and predictors of favorable neurologic patients at discharge.

Results During the study period, 67 patients with CA caused by cardiac events (acute coronary syndrome, 57 patients; idiopathic ventricular fibrillation, 10 patients) were included. Of these, 20 patients (29.9%) were classified into the favorable neurological group. No marked difference was observed in the patient characteristics between those with and without a favorable outcome except for in the time from CA to starting ECLS (ECLS initiation time). A short ECLS initiation time resulted in a favorable outcome (37.8±28.1 minutes vs. 53.6±30.7 minutes, p=0.05). The cut-off time of ECLS initiation was 46 minutes, which was prolonged by the temporary return of spontaneous circulation before ECLS (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.34-10.19; p=0.01) and transfer to the angiographic room (OR, 4.07; 95% CI, 1.44-11.53, p=0.008).

Conclusion The early initiation of ECLS (within 46 minutes) might be associated with a favorable neurological outcome for patients with rCA caused by cardiac events.

Introduction The early integration of palliative care into standard cancer treatment has become a global standard. The Palliative care Emphasis program on symptom management and Assessment for Continuous medical Education (PEACE) has been conducted in Japan, and previous studies have reported that the PEACE workshop was able to improve various palliative care skills of participants. However, whether or not the effects of the program are long-lasting and if the program consequently changed physicians' practice with regard to lung cancer patients have been unclear.

Methods Web-based surveys, including the palliative care knowledge test (PEACE-Q), the Palliative Care self-reported Practice Scale (PCPS), and the Palliative Care Difficulties Scale (PCDS), were conducted among lung cancer physicians in Japan. The differences in the survey results between participants and non-participants of the PEACE workshop were examined.

Results Among 923 respondents (455 respiratory physicians, 345 pulmonary surgeons, and 123 others), 519 had participated in the PEACE workshop. The total PEACE-Q score was significantly higher in the PEACE workshop participants than in non-participants (28.0 versus 24.5, p<0.0001). The score was significantly higher in respiratory physicians than in pulmonary surgeons (27.4 versus 25.5). The total PCPS and PCDS scores were also significantly better in workshop participants than in non-participants (71.8 versus 67.1 and 34.3 versus 36.9, respectively), although some domains of PCDS were similar between the groups.

Conclusion The PEACE program improved the knowledge and practices with regard to palliative care and resolved difficulties associated therewith among lung cancer physicians. In regions where palliative care specialists are insufficient, such educational programs may be effective.

Mini Abstract The PEACE program improved the knowledge and practices with regard to palliative care and resolved difficulties associated therewith among lung cancer physicians in Japan.

Hypertensive emergency, which occurs even in young adults, induces systemic organ damage and results in a poor prognosis. We herein report the case of a 27-year-old man who developed alveolar hemorrhaging with hypertensive emergency. He presented with bloody sputum, renal failure, and extremely high blood pressure (200/128 mmHg). Chest computed tomography revealed diffuse bilateral alveolar infiltrates suggestive of diffuse alveolar hemorrhaging. After intensive therapy with anti-hypertensive drugs, the alveolar hemorrhaging disappeared. Renal impairment was partially reversed. Therefore, we conclude that hypertensive emergency should be considered as a possible cause of hemoptysis, even in young adults.

A 45-year-old man was admitted due to tonic seizures, aphasia, disturbance of consciousness, and abnormal behavior. Because cerebral magnetic resonance imaging findings were normal and mild cerebrospinal fluid (CSF) pleocytosis was observed, autoimmune encephalitis was suspected. The presence of anti-N-methyl-D-aspartate (NMDA) receptor antibodies in the CSF was subsequently confirmed. ¹²³I-Iomazenil and cerebral blood flow single photon emission computed tomography (SPECT) revealed an abnormal uptake in the left frontotemporal region. Multimodal immunotherapy was administered, which remarkably improved the level of consciousness. Progressive reversibility of SPECT findings with clinical improvement suggested that the disorder-related functional deficits had been caused by anti-NMDA receptor antibodies.

Objective Few reports have analyzed the diagnostic process of carcinoma of unknown primary site (CUP) or have focused on the frequency of nonmalignant lesions among patients with suspected malignant diseases. The aim of this study was to investigate the incidence and characteristics of nonmalignant diseases that tend to be mistaken for malignant diseases.

Patients We retrospectively analyzed the medical records of patients with suspected CUP who were referred to the National Cancer Center Hospital (Tokyo, Japan) between April 2007 and December 2014. All patients underwent a thorough history and physical examination as well as radiological and ultrasonography imaging tests for the CUP diagnostic work up.

Results Among 830 patients with suspected CUP, 46 were diagnosed with nonmalignant diseases, and 780 were diagnosed with a malignant neoplasm (409 neoplasms with detected primary site and 371 CUP neoplasms). Four patients discontinued the diagnostic workup because they refused further examinations or had a poor general status. The final diagnosis of the 46 patients with nonmalignant disease comprised 10 benign tumors, 10 benign diseases, and 26 with no evidence of disease. The nonmalignant tumors comprised three hemangiomas, two schwannomas, two uterine myomas, two pseudomyxoma peritonei, one lymphangioma, one meningioma, and one poroma.

Conclusions The incidence of nonmalignant diseases among patients with suspected CUP was 46 out of 830 patients in our institution. It is important to perform a thorough pathological examination in the CUP diagnostic workup. To confirm a diagnosis, some patients may need to visit specialized institutions, especially those with liver and bone lesions.

Background A subset analysis of the LETS study suggested that S-1 plus carboplatin was more beneficial than paclitaxel plus carboplatin in terms of the overall survival (OS) in squamous cell lung cancer. However, the benefit of maintenance therapy for squamous cell non-small cell lung cancer (NSCLC) patients is still unknown. We herein report a phase II study to evaluate the efficacy and safety of a tailored dose of S-1 plus carboplatin followed by maintenance S-1 in chemotherapy-naive advanced squamous cell NSCLC.

Methods Patients received carboplatin on day 1 plus S-1 on days 1 to 14 every 21 days. The dose of S-1 was determined by the body surface area and creatinine clearance. After four cycles of induction, non-progressive patients continued to receive S-1 until disease progression or unacceptable toxicity occurred. The primary endpoint was an objective response rate (RR) with a threshold value of 15%. The secondary endpoints were the progression-free survival (PFS) and OS from enrollment, the PFS in the maintenance phase, and safety.

Results In the 33 patients analyzed, the rate of patients who met the primary endpoint was 30.3% (95% confidence interval: 15.6%-48.7%), and the disease control rate was 75.8%. The median PFS and OS were 3.5 and 11.3 months, respectively. Ten patients received maintenance S-1, and the median PFS from the beginning of induction treatment was 5.3 months. Grade 3/4 toxicities with a frequency of more than 5% were all controllable.

Conclusions Tailored-dose S-1 plus carboplatin followed by maintenance S-1 is an effective and feasible treatment for advanced squamous cell NSCLC.

We herein report a teenage girl who had been taking oral contraceptive pills for three months and complained of left lower abdominal pain that had continued for two months. A physical examination indicated anterior cutaneous nerve entrapment syndrome (ACNES), although no abnormality was found in various biochemical and imaging examinations. The pain was only transiently ameliorated by trigger-point injection, and neurectomy surgery was eventually effective. Sex steroids can be involved in the progress of local tissue edema causing ACNES. ACNES should be considered in cases of abdominal pain in patients taking oral contraceptives.

Sudden death as a result of multiple system atrophy (MSA) is usually attributed to vocal cord paralysis or disruption of breathing owing to the degeneration of the brainstem respiratory centers. However, the exact pathophysiology of sudden death is still unclear. In addition, specific causes of sudden death are not always investigated by an autopsy. We herein report a patient with MSA and non-aneurysmal subarachnoid hemorrhaging, which is believed to be a rare cause of death in this setting. Without an autopsy, our case would likely have been diagnosed as sudden death due to vocal cord paralysis. To develop effective strategies to prevent sudden death, a post-mortem investigation is important in order to exclude known structural causes of death.

A 64-year-old woman with no previous mental illness took a single 500 mg tablet of levofloxacin for cystitis. Two hours later, she developed psychosis with involuntary movement and severe hyperventilation with respiratory alkalosis. Cranial magnetic resonance imaging findings were unremarkable, and an electroencephalogram revealed no epileptiform discharge. Her symptoms improved on the third day after levofloxacin was discontinued. Levofloxacin-associated encephalopathy with psychotic features is a rare adverse event. Disturbance of GABAergic interneurons by levofloxacin may lead to hyperventilation via dysfunction of the brainstem respiratory network. Physicians should be aware of hyperventilation as an additional serious symptom of levofloxacin-associated encephalopathy in acute settings.

Bronchial thermoplasty, which delivers thermal radiofrequency to the bronchial wall, is an effective therapy for patients with severe persistent uncontrolled asthma. We herein report the case of a 47-year-old man who underwent bronchial thermoplasty for uncontrolled severe asthma. After bronchial thermoplasty, his asthma control, asthma-related quality of life, and pulmonary function improved. Furthermore, a histologic examination of transbronchial biopsy specimens revealed a decrease in goblet cell hyperplasia and the smooth muscle mass as well as in the subepithelial basement membrane thickness. Bronchial thermoplasty can be effective for patients with severe uncontrolled asthma and mucus hypersecretion.

Acute chest syndrome (ACS), characterized by fever, respiratory symptoms, and new pulmonary infiltration, is a serious complication of sickle cell disease (SCD). Regardless of the etiology, the conventional treatment options for ACS include empirical antibiotic therapy, the administration of analgesics, and red cell transfusion. The indications and methods of red cell transfusion are critical. We herein report the case of a 26-year-old African-American man with SCD who developed ACS and who was successfully treated with manual exchange transfusion. Despite increasing globalization, SCD remains extremely rare in Japan. Manual exchange transfusion can be performed easily anywhere and should be considered for treating SCD patients presenting with ACS.

A 35-year-old man with refractory Crohn's disease showed a loss of response to infliximab after requiring treatment with infliximab at 10 mg/kg together with steroid to maintain remission. His symptoms recurred, and colonoscopy showed extensive active ulcers in the colon. Adrenomedullin therapy was started in addition to the conventional infliximab therapy. A few days after, his symptoms went into remission. Endoscopy at 2 and 7 weeks revealed significant mucosal remission without steroid therapy. Adrenomedullin promoted mucosal healing and led to the re-induction of remission in Crohn's disease in a patient with a loss of response to infliximab.

Objective The fecal occult blood (FOB) test is commonly used for colorectal cancer screening; however, it is uncertain if further diagnostic interventions, such as a colonoscopy, should be performed based on its results.

Method To better understand patient behavior following the FOB test, 6414 patients (3807 men and 2607 women) who underwent colonoscopy between August 2015 and March 2016 at any of the 26 medical institutions throughout Hiroshima Prefecture were invited to participate in the study. All patients provided their written consent, after which they completed a questionnaire, and their colonoscopy results were obtained. These datasets were analyzed in a blinded manner, and the unique codes linking the records were revealed at the end of the analysis.

Results Of the total study population, 4749 patients (74.0%) had previously undergone FOB testing. After classification of common behavioral responses that the patients displayed following their FOB test, the group who had undergone the test several times, who had not had positive test results in the past, and whose latest FOB test results were positive had a significantly higher diagnosis rate of both early- and advanced-stage cancer than the other groups. Furthermore, patients in whom several previous FOB test results had been negative whose previous colonoscopy was positive were associated with a higher diagnosis rate of early-stage cancer than other groups.

Conclusion These results suggested that colonoscopy should be performed immediately for patients with positive FOB test results due to their association with colorectal cancer and the possible detection of cancer at an early stage.

We documented four cases of systemic lupus erythematosus (SLE) presenting with pleuritis as the initial disease manifestation. The diagnosis was challenging because, atypically, all patients were elderly and 3 of the 4 patients were men. Furthermore, SLE pleuritis, characterized by lymphocytic pleural effusion and high ADA activity, is difficult to differentiate from tuberculous pleurisy. A detailed physical examination, blood tests, and urinalysis are therefore indispensable to ensure an accurate diagnosis.

We also reviewed the previously published case reports on SLE patients presenting with pleuritis and discussed the relevant findings.

Objective Salt loading induces renal damage independently of blood pressure (BP) elevation via reactive oxygen species and sympathetic activity. Melatonin, a hormone that regulates the circadian rhythm, has multiple functions, including anti-oxidant effects and the inhibition of sympathetic activity. We have shown that impaired melatonin secretion is associated with renal damage in chronic kidney disease (CKD) patients. However, the associations between salt loading, melatonin secretion, and urinary albumin and protein have not been clarified.

Methods We recruited 32 CKD patients, conducted 24-hour ambulatory BP monitoring and collected daytime and nighttime urine while the patients were consuming a standard salt (10 g/day) or low salt (6 g/day) diet. The excretion levels of albumin, protein and 6-sulfatoxymelatonin (aMT6s), a metabolite of melatonin, in daytime and nighttime urine were investigated in patients consuming standard salt and low salt diets.

Results The urinary aMT6s levels in daytime and nighttime of the patients consuming standard salt and low salt diets did not differ to a statistically significant extent. However, the urinary aMT6s levels in patients consuming a standard salt diet-but not patients consuming a low salt diet-were significantly and negatively correlated with the daytime and nighttime urinary albumin and protein levels. Contrarily, no significant correlations were found between the urinary aMT6s levels and the BP levels, renal function, and plasma angiotensin II levels in patients consuming either a standard salt or low salt diet. A multiple regression analysis adjusted for age, sex, and body mass index revealed that the urinary albumin and protein levels were significantly and negatively associated with the urinary aMT6s levels in patients consuming a standard salt diet, but not in patients consuming a low salt diet.

Conclusion Salt loading aggravates the relationship between melatonin secretion and albuminuria or proteinuria.

A 73-year-old man developed diplopia after the administration of pembrolizumab for lung adenocarcinoma. He had ptosis and external ophthalmoplegia without general muscle weakness. Serum CK levels were elevated. Although autoantibodies to acetylcholine receptor and muscle-specific kinase, the edrophonium test, and the repetitive nerve stimulation test were all negative, anti-titin autoantibody was positive, leading to the diagnosis of myasthenia gravis (MG). Muscle pathology showed necrotizing myopathy with tubular aggregates. Unlike previously reported cases of pembrolizumab-associated MG, the present case showed ocular MG. This is the first case of pembrolizumab-associated MG with anti-titin antibody, as well as the first case with tubular aggregates.

Recurrence of an embolized pulmonary arteriovenous malformation (PAVM) is common after coil embolization. A 23-year-old woman who had undergone multiple instances of transcatheter coil embolization was admitted with hypoxia and hemoptysis. A PAVM in the left S6 was found to be recanalized by reperfusion through the pulmonary and bronchial arteries. The left S6 was partially resected; the specimen contained necrotic granulomas and non-tuberculous mycobacteria (NTM) around the PAVM. Clinicians should consider possible recurrence of PAVM after reperfusion of the pulmonary and bronchial arteries, as well as the risk of NTM infection during follow-up of patients who have undergone repeated coil embolization.

A 70-year-old woman was admitted for the evaluation of wheezes and a nodular lesion in the left lung field. She had been diagnosed with rheumatoid arthritis at 45 years of age and was continuously treated with methotrexate (MTX) at 8 mg/week. Bronchoscopic aspiration histology of a hilar lymph node suggested a lymphoproliferative disorder (LPD). After discontinuation of MTX, the lung nodule and wheezes disappeared. Although wheezes are not a usual manifestation of LPD, her clinical course clearly demonstrated an obvious relationship between LPD-induced airway narrowing and wheezes.

Pulmonary artery (PA) sling is a congenital disease in which the left PA abnormally arises from the right PA and is usually diagnosed during the infantile period. We present an adult case of PA sling accompanied by tracheobronchomalacia found in a 49-year-old woman with a history of recurrent pneumonia. Computed tomography of the chest showed that the left lung was nourished by two aberrant PAs. Bronchoscopy demonstrated achondroplasia of the trachea and the right bronchus, which we speculate to have resulted in their stenosis. The recurrent pneumonia was attributable to these tracheobronchial structural abnormalities; we therefore stress the importance of focusing on the anatomic abnormalities in such cases.

A 69-year-old woman was admitted to our hospital with a fever, dizziness, and headache caused by Neisseria meningitidis. After ceftriaxone was administered, she suddenly developed bilateral oculomotor nerve palsy. Intra-orbital magnetic resonance imaging using appropriate sequences revealed that her bilateral third intracranial nerves were enlarged and enhanced. She achieved complete recovery by two months after additional short-term treatment with intravenous immunoglobulin and methylprednisolone. Although intracranial nerve disorders that result from bacterial meningitis are most frequently reported in children, it is noteworthy that it can also cause focal intracranial nerve inflammation with ophthalmoparesis in N. meningitidis infection in adults.

Lymphoproliferative disorders can occur in patients with autoimmune disorders who undergo long-term methotrexate therapy (MTX-LPD). Although the manifestations of MTX-LPD are diverse, little attention is paid to endobronchial involvement. We herein describe two patients with MTX-LPD who presented with parenchymal pulmonary tumors and endobronchial involvement of LPD; one had lymphomatoid gramulomatosis and the other LPD. The patients had no tumors adjacent to the endobronchial lesions. The endobronchial findings included multiple protruded mucosal lesions covered with white material, which was pathologically consistent with LPD. Recognition of the findings may help in making an earlier diagnosis of MTX-LPD in appropriate settings.

Hypercalcemia is a severe complication in cases of vitamin D intoxication that can result in metastatic calcification. We herein report a female case with hypercalcemia due to eldecalcitol administration associated with the increased uptake of technetium-^99mhydroxymethylene diphosphonate (^99mTc-HMDP) as the bone-scanning agent in the stomach. A histologic assessment using biopsy specimens identified metastatic calcification of the stomach. After the normalization of serum calcium levels, the gastric uptake of ^99mTc-HMDP disappeared. This case indicates the usefulness of bone scintigraphy with ^99mTc-HMDP to detect visceral metastatic calcification and to monitor its therapeutic effects in patients with hypercalcemia.

We herein report a case of the beneficial effect of osimertinib readministration in non-small-cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation. A 69-year-old non-smoking woman was diagnosed with advanced NSCLC harboring an EGFR ex19 deletion and T790M. She was treated with osimertinib for two years but eventually acquired resistance. After 1.5 years of salvage chemotherapies, osimertinib was re-administered. She has been effectively and safely treated with osimertinib readministration for over 10 months. A prospective study is warranted to evaluate the efficacy and safety of osimertinib readministration in NSCLC with EGFR mutations.

An 81-year-old Japanese man with no history of diabetes mellitus was admitted to our hospital for a fever with a new ulcerative lesion on the left heel. Blood cultures on admission grew Arcanobacterium haemolyticum in aerobic bottles. He was therefore diagnosed with A. haemolyticum bacteremia and osteomyelitis complicated with foot decubitus ulcer. He was successfully treated with intravenous antibiotic therapy and debridement of the left heel. Our case and literature review show that it is important to recognize that A. haemolyticum is a systemic causative pathogen in immunocompetent patients in primary care practice.

A 73-year-old man with liver cirrhosis and advanced chronic kidney disease was admitted to our hospital due to bilateral lower leg edema and appetite loss. Furosemide to treat fluid retention markedly decreased extracellular water compared with intracellular water, but the addition of tolvaptan equally decreased both with a greater diuretic response than furosemide alone. Furthermore, tolvaptan administration increased the plasma colloid osmotic pressure, which might facilitate the shift of fluid from the extravascular space to the intravascular space. This is the first case showing different effects on the fluid distribution between furosemide and additional tolvaptan in the same patient.

We report a case of Nocardia exalbida (N.exalbida)-induced pneumonia in a 70-year old Japanese man with lung cancer and radiation pneumonitis. He initially received doripenem (1.5 g/day) for pneumonia treatment, and N.exalbida was identified by a clone library analysis of bronchoalveolar lavage fluid obtained from the pneumonia lesion. The doripenem dosage was therefore increased to 3.0 g/day with adjunctive trimethoprim/sulfamethoxazole, and his pneumonia improved. N. exalbida is susceptible to antibiotics; thus, in nocardiosis, N. exalbida infection might be associated with a good response to treatment, although its clinical findings are non-specific and similar to those of other Nocardia infections.

Although multiple myeloma (MM) had been an incurable hematological malignancy with a poor prognosis, recent advances in novel anti-neoplastic agents, including carfilzomib (a proteasome inhibitor), have improved the prognosis. We herein report two cases of congestive heart failure in patients treated with carfilzomib. Although there are some reports on the cardiotoxicity of carfilzomib, to our knowledge, this is the first report on the cardiac involvement of carfilzomib in Japanese MM patients. We review the critical points from our two cases, with the aim of avoiding carfilzomib-associated heart failure in MM patients.

Objectives Sound hypersensitivity is highly comorbid with migraine headaches. To elucidate the pathogenic mechanism of migraine attacks, we must first identify the types of everyday environmental sounds they perceive as unpleasant and clarify the acoustic properties of such sounds. This study aimed to clarify the true nature of "noise," i.e. everyday sounds perceived as unpleasant by migraineurs, by evaluating their subjective comfort/discomfort in response to several sounds commonly heard in everyday life.

Methods Participants were presented with 20 environmental sounds they would likely hear daily. Subjects rated the pleasantness/unpleasantness of each stimulus using a nine-step scale.

Patients We recruited 50 adults with migraine headaches (46 women, 4 men) and 50 healthy controls (35 women, 15 men).

Results Migraineurs provided statistically significantly lower (more unpleasant) ratings to ambulance sirens, police car sirens, and railroad crossing bells than did controls. Our analysis also investigated the acoustic characteristics associated with higher rating gaps between the two groups. Greater divergence in ratings for the same stimulus was associated with less power (smaller amplitude envelope) and slower temporal variation in signals in the 400-Hz band.

Conclusion We identified specific signal components associated with different subjective (un) pleasantness scores between migraineurs and healthy adults, which may lead to the elucidation of the pathogenic mechanism underlying migraine attacks triggered by sound.

Autoimmune pancreatitis (AIP) is now considered a pancreatic manifestation of a newly proposed disease condition, IgG4-related disease (IgG4-RD). IgG4-RD is characterized by enhanced IgG4 antibody responses and multiple organ involvements. Recent epidemiological studies have addressed the incidence of cancer in patients with AIP and/or IgG4-RD. Surprisingly, a significant number of AIP patients were detected with cancer at or within one year of the diagnosis of AIP. Furthermore, around 50% of all cancers detected in AIP patients comprised mainly 3 types (gastric, lung, and prostate cancer). Thus, AIP appears to be associated with cancer of other organs rather than the pancreas itself, which suggests that AIP is not a pre-cancerous condition of the pancreas. Moreover, the simultaneous occurrence of cancer and AIP in many patients has led to the establishment of an attractive concept that AIP might sometimes arise from co-existing cancers as a paraneoplastic syndrome.

Objective We evaluated the efficacy of vonoprazan-based eradication therapy for Helicobacter pylori, including the effects of age, gender, and grade of atrophy in comparison to proton pump inhibitor-based therapy.

Method We retrospectively reviewed the records of 1172 patients who received first-line triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor or vonoprazan for H. pylori eradication, as well as 157 patients treated with second-line therapy consisting of amoxicillin, metronidazole, and vonoprazan or a PPI.

Results The eradication rate of all cases treated with first-line triple therapy was 86.9% (1,019/1,172), while that in those treated with vonoprazan-based therapy was 92.5% (384/415). Our analysis showed that the use of vonoprazan resulted in a significantly improved success rate of first-line eradication therapy in comparison to proton pump inhibitor-based therapy (OR, 2.36; 95% CI 1.55 to 3.56). The superiority of vonoprazan was remarkable in non-elderly patients, while its effect was unclear in elderly patients. When used as second-line eradication therapy, the advantage of vonoprazan over proton pump inhibitor administration was not clear.

Conclusion The inclusion of vonoprazan increased the success rate of first-line eradication therapy; however, the advantage was reduced with aging and remained unclear in elderly patients.

A 53-year-old man with recurrent episodes of large joint pain and a low-grade fever at irregular intervals for 16 years developed right knee and ankle arthralgia, watery diarrhea, and abdominal pain. Following an ileum and colon biopsy, he was diagnosed with gastrointestinal amyloidosis. We suspected familial Mediterranean fever (FMF) based on his history and administered colchicine; his symptoms subsequently improved. Thus, he was diagnosed with atypical FMF. After tocilizumab administration, the amyloid deposits disappeared. This case suggests that physicians should consider FMF even in cases with atypical symptoms in order to prevent the progression of amyloidosis and that amyloid deposits can be eliminated by IL-6 inhibition.

A 66-year-old man was admitted to our hospital because of multiple refractory skin ulcers. Based on his severe systemic arterial calcification and severe calcium-phosphate imbalance due to severe kidney dysfunction, we initially considered calciphylaxis. However, a skin biopsy provided a diagnosis of cholesterol crystal embolization. Although we initiated hemodialysis, steroid treatment, and low-density lipoprotein-cholesterol apheresis, he died of multiple intestinal perforation. An autopsy showed cholesterol crystals occluding multiple organ arterioles. This case suggests that skin ulcers in patients with chronic kidney disease may be an important diagnostic hallmark and may be associated with several serious diseases.

Background Tracheoarterial fistula (TAF) is a rare but devastating complication of tracheostomy caused by pressure necrosis from the elbow, tip, or over-inflated cuff of the tracheostomy tube. The incidence of TAF is reportedly higher in patients with neurological disorders than in those without such disorders.

Objective To evaluate the incidence of and factors contributing to the misalignment of tracheostomy tubes in bedridden patients with chronic neurological disorders.

Methods We retrospectively assessed three-dimensionally reconstructed serial computed tomography (CT) images to see if the tip of the tube made contact with the tracheal wall and if the main arteries were running adjacent to the tube's elbow, tip or cuff.

Results The tip of the tube was in contact with the tracheal wall in 14 of the 30 patients assessed. Among them, the tip was adjacent to the innominate artery in eight, the aortic arch in three and an aberrant right subclavian artery in one. In one patient with the tube tip adjacent to the aortic arch and the other four patients, the cuff of the tube was adjacent to the innominate artery across the tracheal wall. Patients with the tube tip in contact with the anterior tracheal wall had a significantly greater cervical lordosis angle than those without contact (p<0.05).

Conclusion More than half of tracheostomized patients with chronic neurological disorders had a latent risk of TAF. The variability in the location of the innominate artery, anomalies of the aortic arch, and skeletal deformities may therefore be contributing factors.

We performed split drug-eluting bead transarterial chemoembolization (DEB-TACE) in a patient with huge unresectable hepatocellular carcinoma and multiple intrahepatic metastases. However, TACE was discontinued at the fourth application because the tumor was fed by the cholecystic artery. As most intrahepatic metastases disappeared following DEB-TACE, the patient was able to undergo radical hepatectomy, and has maintained a complete response.

DEB-TACE enables cancer treatment without reducing the liver or renal function. However, it is associated with a risk of ischemia in other organs in patients whose arteries feed both tumors and other organs; thus appropriate selection is required.

Objective The incidence of osteoporosis is increasing with the rapid aging of the Japanese population. Bisphosphonates are first-line agents used for the treatment of osteoporosis, but they can cause upper gastrointestinal mucosal injury. This study investigated symptoms and upper gastrointestinal mucosal injury associated with oral bisphosphonates.

Methods Symptoms were evaluated using the F-scale questionnaire, and esophageal mucosal injury and gastroduodenal ulceration were assessed by endoscopy. Patients were stratified by the type of bisphosphonate (alendronate, risedronate, or minodronate), treatment schedule (once weekly or every four weeks), and the concomitant use of other medications (antithrombotic agents, nonsteroidal anti-inflammatory drugs [NSAIDs], or acid suppressants).

Patients The subjects included 221 patients treated with oral bisphosphonates for at least one month.

Results The median F-scale total score was 4 (0-34), reflux score was 2 (0-20), and the mean dyspepsia score was 2 (0-16). Endoscopy showed esophageal mucosal injury of Grade A or worse (Los Angeles classification) in 22/221 patients (10.0%) and gastroduodenal ulcers in 9 patients (4.1%). The dyspepsia score in patients who took minodronate every four weeks was significantly lower (p<0.05) in comparison to patients who took other bisphosphonates. The dyspepsia score was significantly higher (p<0.05) and mucosal injury was significantly more frequent in patients who also used antithrombotic agents and NSAIDs.

Conclusion Symptoms and upper gastrointestinal mucosal damage were not necessarily frequent or severe in patients treated with bisphosphonates. However, the concomitant use of bisphosphonates with antithrombotic agents and NSAIDs increased both symptoms and mucosal injury. The symptoms were milder in patients using minodronate once monthly.