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 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, 6,414 patients (3,807 men and 2,607 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, 4,749 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.

Objective We evaluated the efficacy of vonoprazan-based eradication therapy for Helicobacter pylori (H. 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 1,172 patients who received first-line triple therapy with amoxicillin, clarithromycin, and vonoprazan or a proton pump inhibitor (PPI) 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 [odds ratio (OR), 2.36; 95% confidence interval (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 PPI 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.

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.

Objective 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.

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.

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.

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-99m hydroxymethylene 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.

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.

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.

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.

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.

Bronchial thermoplasty (BT), 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 BT for uncontrolled severe asthma. After BT, 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. BT can be effective for patients with severe uncontrolled asthma and mucus hypersecretion.

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.

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.

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 exon19 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.

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 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.

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.

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.

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.

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.