Objective Human intelectin-1 (hITLN-1) binds to galactofuranosyl residues, which are present in the microbial cell wall, but which are absent in mammalian tissues, and has been suggested to play an immunological role against microorganisms. However, the involvement of hITLN-1 in the pathogenesis of diffuse pulmonary diseases remains unknown. The aim of this study was to compare the hITLN-1 concentrations in the bronchoalveolar lavage (BAL) fluid of patients with diffuse pulmonary diseases.
Methods The cell components and concentrations of hITLN-1 were analyzed in the BAL fluid of 8 patients with idiopathic chronic eosinophilic pneumonia (ICEP), 3 patients with drug-induced eosinophilic pneumonia, 4 patients with hypersensitivity pneumonitis (HP), 11 patients with sarcoidosis, 9 patients with cryptogenic organizing pneumonia, and 5 patients with idiopathic fibrosing interstitial pneumonia (fibrosing nonspecific interstitial pneumonia or usual interstitial pneumonia).
Results The hITLN-1 concentrations in the BAL fluid of patients with ICEP and HP were higher than in those with other diseases. In the ICEP group, no significant difference was observed in the hITLN-1 concentrations of patients with or without a history of bronchial asthma.
Conclusion The results of the present study suggest that hITLN-1 may be involved in the pathogenesis of ICEP and HP, and that an increase in the hITLN-1 concentration in the BAL fluid may represent a new biomarker for these diseases.
Objective Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure for pulmonary and mediastinal diseases. This study compared the performance of a novel 19-G needle with a 21- or 22-G needle.
Patients and Methods Eleven patients at Okayama Medical Center were enrolled retrospectively between April and December 2017. Enlarged lymph nodes and a pulmonary nodule were sampled with both 19-G and 21- or 22-G needles in nine patients. Two patients underwent biopsies for suspected lymphoma with only the 19-G needle. We examined their medical records on the diagnosis, size of the lymph nodes and pulmonary nodule, and complications.
Results The median longest diameter of the 13 lymph nodes (8 #7, 4 #4R, and 1 #11) and 1 pulmonary nodule (right segment 6) in the 11 patients was 31.6 mm (range, 10.4-45.0 mm). Definitive diagnoses were made using the 19-G needle in nine patients. EBUS-TBNA with a 19-G needle resulted in successful diagnoses of one case of retinal hemangioblastoma, one case of tuberculous lymphadenitis, and one case of lung adenocarcinoma, as well as the evaluation of the programmed death-ligand 1 (PD-L1) expression following initial negative findings after a 21- or 22-G biopsy. A small pulmonary nodule (lung squamous cell carcinoma) with negative findings after a 19-G biopsy was diagnosed with a 22-G biopsy. Two suspected lymphoma patients were diagnosed with a 19-G needle: one had lymphoma and the other sarcoidosis. Three patients were diagnosed with sarcoidosis using both the 19-G and 21- or 22-G needles.
Conclusion EBUS-TBNA with a 19-G needle was useful for diagnosing retinal hemangioblastoma and tuberculous lymphadenitis as well as for PD-L1 testing after 21- and 22-G biopsies were unsuccessful.
Objective Although R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) is a standard therapy for diffuse large B-cell lymphoma (DLBCL), the optimal dose for elderly patients remains unclear.
Methods and Patients We retrospectively verified our R-CHOP dose-attenuation system implemented from 2005 for DLBCL patients. Among the 115 DLBCL patients treated during 2001-2010, 33 patients treated during 2001-2005 received R-CHOP doses adjusted according to physicians' decisions (PHY group). Eighty-two patients treated after 2005 received adjusted R-CHOP doses according to a unified dose-attenuation system (UNI group). Patients aged <60, 60-69, 70-79, and ≥80 years received the standard R-CHOP, 100% R-CHO+P (50 mg/m2), 100% R+75% CHO+P (40 mg/m2), and 100% R+50% CHO+P (30 mg/m2), respectively. We compared the responses, survival, and treatment cessation between the PHY and UNI groups.
Results The patients' characteristics between both groups were closely comparable. All PHY patients received randomly adjusted R-CHOP doses; 94% of UNI patients received scheduled doses. The complete response rates differed significantly between the UNI (77%) and PHY patients (50%) (p=0.011). The two-year event-free survival rates were 50% and 32% in the UNI and PHY groups, respectively (p=0.0083). The two-year OS rates were 77% and 72% in the UNI and PHY group (p=0.16). Among the patients aged >70 years (n=59) overall survival was shorter in the PHY group (62%) than in the UNI group (72%; p=0.02). The UNI group received higher anti-tumor agent doses than the PHY group. The therapy discontinuation rates were 5% in the UNI group and 24% in the PHY group.
Conclusion Carrying out unified dose reduction may improve the efficacy and prognosis among elderly DLBCL patients.
A 79-year-old woman was referred for pancreatic tail cancer with multiple liver metastases. The pancreatic tail tumor was diagnosed as acinar cell carcinoma (ACC) histologically by endoscopic ultrasound-guided fine-needle aspiration. Because of multiple liver metastases, S-1 chemotherapy was administered, resulting in a partial response to chemotherapy one year later. After approximately three years, liver atrophy and esophageal varices developed. We suspected S-1 as the cause of the liver cirrhosis. S-1 cessation minimized ascites and improved the esophageal varices. Although S-1 can potentially treat ACC, we should be watchful for liver cirrhosis caused by its long-term administration.
A 20-year old man was diagnosed with fibrolamellar hepatocellular carcinoma (FLHCC) with multiple lung metastases, and chemotherapy with FOLFOX was administered. Contrast enhanced CT after 3 cycles of FOLFOX showed no disease progression. We therefore performed surgical resection and radiofrequency ablation of the liver lesions and lung metastases, after obtaining the patient's informed consent. The liver lesions and lung metastases tested positive for DNAJB1-PRKACA. The treatment for FLHCC with extrahepatic metastasis has not been established; however, in a few cases, good long-term prognoses were obtained with multidisciplinary therapy. We herein report a case of FLHCC with multiple lung metastases that was treated with multidisciplinary therapies.
A 76-year-old woman with hereditary hemorrhagic telangiectasia (HHT) showed elevated serum hepatobiliary enzyme levels, and abdominal imaging studies revealed a hepatic tumor. Her serum alpha-fetoprotein level was 759.5 ng/mL. A pathological examination after hepatectomy confirmed a diagnosis of hepatocellular carcinoma (HCC). An examination of the surrounding liver revealed dilated vessels and thickened endothelial cells without inflammations. HHT patients without other risk factors (like this patient) reportedly have a lower incidence of common cancers, including HCC, in comparison to the unaffected population. One intriguing hypothesis that might explain the hepatocarcinogenesis in this situation is the ischemic liver cirrhosis theory, which suggests that chronic ischemia may cause parenchymal strain and promote inappropriate hepatocyte proliferation.
The low-density lipoprotein-cholesterol (LDL-C) level of a 38-year-old man diagnosed with acute coronary syndrome was 257 mg/dL. The administration of a proprotein convertase subtilisin-kexin type 9 (PCSK9) antibody in addition to rosuvastatin plus ezetimibe was initiated, reducing his LDL-C level to 37 mg/dL. A genetic analysis revealed both an LDL receptor (LDLR) mutation and a PCSK9 V4I mutation. Nine months after revascularization, intravascular ultrasound revealed plaque regression in the coronary arteries. LDLR/PCSK9 mutation carriers are prone to coronary artery disease. Intensive LDL-C lowering by including PCSK9 antibody was associated with coronary plaque regression, suggesting the expectation of prognosis improvement.
A 67-year-old woman was admitted to our hospital due to an acute onset of consciousness disturbance, aphasia and left hemiplegia. Computed tomography revealed multiple systemic infarctions, including brain, kidney and spleen. Transesophageal echocardiography revealed vegetations attached to the mitral valve leaflets, which was suspected to be the embolic source. Repeated blood cultures were negative, and advanced lung cancer was incidentally revealed by computed tomography. She was then diagnosed with nonbacterial thrombotic endocarditis (NBTE) based on the overall clinical picture. Subsequently, extensive systemic embolization repeatedly occurred, and she eventually died 25 days after admission. The autopsy proved NBTE and advanced-stage lung adenocarcinoma.
Pericardial cysts are rare abnormalities and are usually asymptomatic. Although several case reports on their diagnosis and treatment have been published, those on hemorrhagic pericardial cysts remain limited. We herein report the case of a 70-year-old man with a hemorrhagic pericardial cyst complicated with constrictive pericarditis 2 years after the initial diagnosis.
A 79-year-old man was admitted because of complete heart block. Echocardiograms showed an abnormal mass adjacent to the sinus of Valsalva. Subsequent surgical resection was not successful. Despite chemotherapy, the patient died from multiple organ failure. It is important to recognize that approximately 80% of cases of cardiac lymphoma are diffuse large B-cell lymphoma, which is the only malignant neoplasm that may respond well to chemotherapy with rituximab. In order to save patients' lives, the early implementation of chemotherapy with rituximab is critical and should be considered as a therapeutic diagnostic option in select patients.
A 43-year-old woman presented with worsening shortness of breath and lower-extremity edema. Echocardiography and computed tomography showed obstruction of blood flow due to a mass filling the right atrium. Emergency surgery was performed for circulatory failure. Primary cardiac rhabdomyosarcoma was diagnosed based on a histological examination. The patient died about two months after the diagnosis despite surgical excision and radiation therapy. The poor prognosis may have resulted from the grossly incomplete removal of the tumor and chemotherapy intolerance. We herein report a case of primary cardiac rhabdomyosarcoma filling the right atrium and offer possible reasons for the poor prognosis.
A 59-year-old non-obese Japanese woman developed diabetes mellitus with a negative glutamic acid decarboxylase autoantibody (GADA) test result. Her hyperglycemia was initially well controlled by oral hypoglycemic agents; however, despite continued treatment the hyperglycemia gradually worsened. As she had endogenous insulin deficiency and tested positive for insulin autoantibody (IAA), insulin therapy was initiated. Few studies have investigated GADA-negative patients with slowly progressive type 1 diabetes mellitus (SPT1D). Our IAA-positive SPT1D patient progressed from the clinical onset of diabetes mellitus to starting insulin therapy relatively quickly (1.5 years), similarly to other previously reported non-obese patients with GADA-positive SPT1D.
Tumoral calcinosis (TC) is a rare benign but aggressive disorder with variable response rates and high recurrence rates despite medical or surgical treatments. We herein report a case of a 28-year-old woman with underlying systemic lupus erythematosus (SLE) who developed diffuse tumoral calcinosis that was successfully treated by lanthanum carbonate. The formation of tumoral calcinosis depends on the supersaturation of calcium and phosphate. Lanthanum carbonate not only has an excellent phosphate-lowering ability but also low gastro-intestinal calcium absorption. It can be considered an effective alternative treatment for tumoral calcinosis if surgical treatment is not feasible.
Patients on hemodialysis often have carnitine deficiency. We herein report a woman who experienced the dramatic improvement of cardiac dysfunction after intravenous L-carnitine administration. We also investigated the myocardial fatty acid metabolism using 123I-labeled β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) before and after L-carnitine therapy, and the impaired metabolism was ameliorated. Taken together, these findings indicate that L-carnitine therapy improved cardiac dysfunction via the amelioration of the abnormal myocardial fatty acid metabolism, at least in part.
Light Chain Proximal Tubulopathy (LCPT) is a rare form of paraprotein-related kidney disease in which monoclonal free light chains damage the proximal renal tubular epithelial cells. We herein report the case of a 78-year-old woman who presented with anemia and kidney dysfunction. Serum and urine protein electrophoresis analyses revealed a monoclonal IgD and λ free light chains. Proximal tubular injury and the accumulation of λ light chains were found by kidney biopsy. Electron microscopy revealed no organized structure suggestive of crystals. LCPT was caused by IgD lambda myeloma and bortezomib and dexamethasone therapy led to very good partial response (VGPR) without a worsening of the kidney function.
We present a case of Dent disease caused by a novel intronic mutation, 1348-1G>A, of the chloride voltage-gated channel 5 (CLCN5) gene. Cultured proximal tubule cells obtained from the patient showed impaired acidification of the endosome and/or lysosome, indicating that the 1348-1G>A mutation was indeed the cause of Dent disease. Although the prevalence of osteomalacia in Dent disease is low in Japan, several factors-including poor medication adherence-caused severe osteomalacia in the current case. Oral supplementation with calcium and native/active vitamin D therapy, with careful attention to medication adherence, led to the improvement of the patient's bone status.
Linezolid is a useful drug for treating drug-resistant tuberculosis. However, the associated toxicities, especially optic neuritis, are a major obstacle for its long-term use. We recently experienced a case of severe optic and peripheral neuropathy during the treatment of multidrug-resistant tuberculosis. The treatment continued for 12 months despite severe optic and peripheral neuropathy. At eight months after the discontinuation of the drug, the optic neuropathy recovered, but the peripheral neuropathy did not. Considering the grave prognosis of drug-resistant tuberculosis, the continuation of linezolid despite neurotoxicity under close observation may be a suitable option.
We herein report a case of pulmonary hyalinizing granuloma (PHG), which is a rare pulmonary mass. A 69-year-old man with no symptoms presented to our hospital because of the appearance of an abnormal shadow on chest X-ray. Computed tomography revealed a right middle-lobe mass with spicula and infiltration into the upper lobe. Since a bronchofiberscopic examination showed no malignant cells in the specimen, the patient underwent thoracoscopic surgery, which revealed PHG. Spiculation and interlobar infiltration, which comprise the characteristic features of primary lung cancer, are uncommon presentations of this rare entity.
Invasive pulmonary aspergillosis (IPA) usually occurs in patients with severe immunodeficiencies involving neutropenia. Underlying lung disease is a well-known risk factor of IPA; however, interstitial lung disease has not been recognized as a risk factor of IPA. We herein report a patient with fibrotic nonspecific interstitial pneumonia who experienced IPA without neutropenia. His IPA was fatal and showed unusually slow disease progression over one month. The computed tomography findings showed only nonspecific consolidation and no typical lesions suggestive of IPA. Finally, the autoptic findings revealed numerous Aspergillus fungi, neutrophilic pulmonary necrosis, and vessels invaded by Aspergillus fungi.
Nivolumab has become the standard second-line chemotherapy for non-small cell lung cancer. A 73-year-old man with stage IV non-small cell lung cancer received 6 cycles of chemotherapy with nab-paclitaxel/carboplatin/bevacizumab followed by 11 cycles of nab-paclitaxel/bevacizumab; however, treatment was stopped due to pneumothorax. One year after therapy started, a nodule appeared in the left upper lung and increased in size. Mycobacterium abscessus subsp. massiliense disease was diagnosed by a sputum analysis. After short antibiotic treatment, nivolumab was administered. Two months after nivolumab treatment, the nodule improved along with a good tumour response. The effectiveness of nivolumab for chronic infectious diseases, such as M. abscessus disease, should be investigated.
A 69-year-old male patient presented with multiple lung nodules revealed by chest-computed tomography (CT) during a preoperative examination for an appendiceal tumor. The nodule diameters ranged from 2-10 mm without either pleural thickening or effusions. A fluorine-18-labeled fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET)/CT scan showed a high FDG uptake in the appendiceal tumor, but almost normal standardized uptake values in the bilateral lung nodules. A CT-guided biopsy led to a diagnosis of pulmonary epithelioid hemangioendothelioma, a rare vascular tumor with a radiological presentation similar to that of a metastatic lung tumor. The present case is the first to describe successful treatment using a CT-guided biopsy instead of more conventional methods.
A 76-year-old asymptomatic man was found to have a mass in the right lower lung field. Although the presence of a mucinous component in the majority of the tumor was shown by magnetic resonance imaging, the presence of cancer cells was suspected by contrast enhancement on computed tomography (CT) and based on the partial accumulation in the marginal regions of the tumor on fluorodeoxyglucose-positron emission tomography (FDG-PET). A transbronchial lung biopsy was non-diagnostic, but resection of the mass resulted in a diagnosis of colloid adenocarcinoma. The findings from combined contrast CT and FDG-PET may raise the suspicion of colloid adenocarcinoma and prompt the consideration of surgical resection.
Epidermal growth factor receptor (EGFR) T790M mutations are the most frequent mechanism of resistance to first- and second-generation tyrosine kinase inhibitors, and osimertinib is an effective treatment for patients with both EGFR-activating mutations and T790M resistance mutations. We describe the case of a 68-year-old woman with lung adenocarcinoma with G719S, S768I, and T790M mutations in which osimertinib treatment was unsuccessful. The patient died of disease progression one month after discontinuing osimertinib treatment. This case suggests that osimertinib may be ineffective for treating patients with uncommon mutations such as G719S when the patient has also acquired a T790M resistance mutation.
Myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis, mainly occur in older patients, but have also been reported in younger patients. A "second peak" occurs in female patients in their thirties, particularly in ET; thus, the management of pregnancy is often discussed.
We herein present the case of a 33-year-old woman with a high platelet count and multiple placental infarcts during delivery who was subsequently diagnosed with ET. Although there are no worldwide guidelines for the management of MPNs in pregnancy, the risk of thrombosis is markedly increased in these patients, and antithrombotic therapy should be considered.
Light chain deposition disease (LCDD) is a rare systemic disorder caused by the deposition of light chain immunoglobulins, which often results in renal impairment associated with either nephrotic syndrome or asymptomatic proteinuria. B-cell neoplasms, such as multiple myeloma and lymphoproliferative disorders, are well-known underlying diseases in LCDD. Some chemotherapy regimens have been reported, but both evidence-based treatment and management for LCDD have yet to be established. We herein report three cases of LCDD treated with lenalidomide-based therapy, resulting in hematologic responses accompanied by a significant reduction in proteinuria and improvement in the renal function. We recommend lenalidomide-based therapy for renal impairment caused by LCDD.
Loss of consciousness occurs in post-hyperventilation apnea, but its pathophysiology remains unclear. We herein report a patient with post-hyperventilation apnea showing spindle activity on electroencephalogram (EEG). The patient was alert and breathing spontaneously before the hyperventilation test, but loss of consciousness and apnea with spindle activity on EEG occurred when the end-tidal CO2 decreased during the hyperventilation test. She recovered consciousness and spontaneous breathing with the disappearance of the spindle activity on EEG when the end-tidal CO2 increased after the hyperventilation test. The loss of consciousness during post-hyperventilation apnea might be due to the focal involvement of the ascending-activating mesodiencephalic reticular formation.
We herein report the case of a 69-year-old woman with rheumatoid arthritis (RA) and malignant lymphoma who developed Helicobacter cinaedi bacteremia after starting rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. She had a recurrent fever and painful erythema for 13 months before the diagnosis was made. This delayed diagnosis was attributable to the underlying RA, which typically presents with various cutaneous manifestations and elevated C-reactive protein levels. The erythema on the thighs, abdomen, and left forearm improved following treatment with intravenous aminobenzyl penicillin; she received antibiotics for six weeks. This case emphasizes the importance of recognizing this opportunistic infection in immunocompromised patients.
Although Stenotrophomonas maltophilia causes substantial morbidity and mortality in immunocompromised patients, it has not been described as a causal pathogen of neutropenic enterocolitis (NEC). We describe the first case of histologically-confirmed NEC caused by S. maltophilia accompanied by bacteremia and pneumonia after salvage chemotherapy for acute myeloid leukemia relapse following a second hematopoietic stem cell transplantation. S. maltophilia should be included as a pathogenic organism of NEC in severely immunocompromised patients to prevent a delayed diagnosis, which carries a high risk of inappropriate antimicrobial selection and fatal outcome.