Is polypharmacy a risk factor for aspiration pneumonia in older adults? A case-control study.

INTRODUCTION: The incidence of aspiration pneumonia and the number of medicines prescribed increase with older age. Many medicines pose a risk for aspiration pneumonia, especially those that decrease swallowing function. Older adults with polypharmacy often receive a combination of these medicines. This study aimed to clarify whether polypharmacy is a risk factor for aspiration pneumonia. METHODS: Older adults aged ≥ 65 years receiving oral medicines were included in this case-control study. Patients hospitalized for pneumonia served as the case group, and other age-matched hospitalized patients served as the control group. Patient data were collected retrospectively, and logistic regression analysis was performed using items that showed significant differences in the univariate analysis as explanatory variables. RESULTS: Logistic regression analysis revealed that the number of medicines was not a risk factor for aspiration pneumonia; however, it was associated with the Functional Oral Intake Scale score, male sex, body mass index, and number of comorbidities. CONCLUSION: Although polypharmacy is often defined only by the number of medicines, it is not a risk factor for aspiration pneumonia. A detailed comparison of prescription medicines between the pneumonia and non-pneumonia groups is necessary.

[Tiny Size Lung Cancer which was not Pathologically Diagnosed before Hilar and Mediastinal Dissection].

A 63-year-old man was found to have abnormally high carcinoembryonic antigen levels in a health examination. Computed tomography scan revealed lymphadenopathy at the right hilum of lung and right upper mediastinum. Malignancy was suggested by endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)for lymph node. Lymph node metastases of lung cancer was suspected, but primary site was unidentified. In order to perform complete hilar dissection, right upper lobectomy was done with systematic mediastinal dissection. Pathological diagnosis was adenocarcinoma of 3 × 3 mm in size in the fibrous scar of the right upper lobe. Immunostaining revealed thyroid transcription factor-1(TTF-1) [+]and paired box-8(PAX-8) [-] indicating the tumor to be a primary lung cancer.

[Recurrence of Anaplastic Lymphoma Kinase Positive Lung Cancer Nineteen-year after the Primary Surgery].

A 77-years-old man who underwent middle lobectomy for lung adenocarcinoma in our hospital 19 years ago. p-Stage IA was pointed out multiple nodules in bilateral lung fields on a medical examination. Computed tomography scan revealed a tumor measuring 34×34 mm in size in the right lower lung and other 40 small pulmonary nodules. Characteristic pattern of metastatic adenocarcinoma from the previous lung cancer was pathologically demonstrated. Immunostaining revealed anaplastic lymphoma kinase (ALK) positivity of the both specimens, which determined the diagnosis of recurrence. Long-team postoperative follow-up for ALK positive lung cancer patients is considered to be necessary especially for younger patients.

Trend of patient characteristics and its impact on the response to adalimumab in patients with rheumatoid arthritis: post hoc time-course analysis of an all-case PMS in Japan.

OBJECTIVES: To investigate the relationship between changes in patient characteristics over time and the effectiveness and safety of adalimumab in the treatment of rheumatoid arthritis (RA) in clinical practice. METHODS: Patients enrolled in the post-marketing registry study in Japan were divided into 5 subgroups based on the time adalimumab treatment was initiated. Demographic and baseline characteristics and responses to adalimumab were compared among the 5 subgroups to detect any time-course trend. Multiple logistic regression analysis was performed to identify characteristics that were significantly associated with the effectiveness or safety of adalimumab and to estimate response rates and the incidence of adverse drug reactions in individual subgroups. RESULTS: During the study period, patient characteristics changed significantly over time, in particular with regard to prior biologic use and concomitant methotrexate therapy. There was a significant trend toward higher response rates and lower incidence of infections and injection-site reactions in patients initiating adalimumab later in the study. Patient characteristics, such as concomitant methotrexate therapy and early stage RA, were significant predictors of the effectiveness and safety of adalimumab. CONCLUSIONS: Patient characteristics have changed since adalimumab became available for the treatment of RA; several of these characteristics were significant predictors of adalimumab effectiveness and safety.

[Pre-evening meal administration of tacrolimus improved refractory ocular symptoms in two young children with latent general myasthenia gravis].

We report two patients with latent general myasthenia gravis (MG) with refractory ocular symptoms who were successfully treated with pre-evening meal administration of tacrolimus. Patient 1 was a 4-year-old girl with persistent ocular symptoms despite high-dose steroid therapy and thymectomy. Oral tacrolimus was initiated at the age of 3 years, which was resulted in complete resolution of symptoms. After one year, hemilateral ptosis recurred. The plasma consentration of tacrolimus was very low, probably due to sudden weight gain. Increasing the dose and a change from post- to pre-evening meal administration of tacrolimus enabled maintenance of its concentration and complete control of ocular symptoms. Patient 2 was a 2-year-old boy whose symptoms were refractory to steroid therapy after his first relapse. Since post-meal administration of tacrolimus provided partial benefit, the closing schedule was changed to pre-evening meal administration, with good results. Neither patient had adverse effects of tacrolimus. It is difficult to maintain an effective tacrolimus concentration in children due to marked growth and rapid metabolic rates. Pre-evening meal administration of tacrolimus is an easy, safe and useful method of treatment in MG young children.

Comparison of three measurements on computed tomography for the prediction of less invasiveness in patients with clinical stage I non-small cell lung cancer.

BACKGROUND: A greater proportion of ground-glass opacity (GGO) is well known to be strongly associated with less invasive lung adenocarcinoma. Recently, the solid area diameter has also been reported to be a simple and better marker for the same purpose compared with the whole nodule diameter. METHODS: From 1997 to 2009, 383 patients with clinical T1-2N0M0 non-small cell lung cancer (NSCLC) with a solid area of 3 cm or less underwent surgical resection, and their preoperative high-resolution computed tomographic images were preserved in Digital Imaging and Communications in Medicine format. Less invasive lung cancer was defined as having no vascular, lymphatic, or pleural invasion or lymph node metastasis. We compared the solid area and whole nodule diameters and proportion of GGO, with the objective of predicting less invasive lung cancer. RESULTS: Among the 383 patients, 187 were men, 335 had adenocarcinoma histologic type, 242 had less invasive lung cancer, and 43 experienced recurrence. Receiver operating characteristic (ROC) analysis to predict less invasive lung cancer showed that the area under the curve of proportion of GGO was the highest (0.848; 95% confidence interval [CI], 0.810-0.886), followed by the solid area diameter (0.785; 95% CI, 0.740-0.829), and then whole nodule diameter (0.621; 95% CI, 0.565-0.677). Multiple logistic regression analyses revealed that proportion of GGO was the only significant predictor of less invasive lung cancer. The proportion of GGO was also found to be a significant prognostic factor of disease-free survival (DFS) along with solid area diameter by multivariate analysis. Regardless of the solid area diameter, no patient with a greater proportion of GGO (> 50%) experienced recurrence. CONCLUSIONS: Proportion of GGO remains important for predicting less invasive lung cancer.

Characteristics of subsolid pulmonary nodules showing growth during follow-up with CT scanning.

OBJECTIVE: The positive results of a screening CT scan trial are likely to lead to an increase in the use of CT scanning, and, consequently, an increase in the detection of subsolid nodules. Noninvasive methods including follow-up with CT scanning, to determine which nodules require invasive diagnosis and surgical treatment, should be defined promptly. METHODS: Between 2000 and 2008, from our database of . 60,000 examinations with CT scanning, we identified 174 subsolid nodules, which showed a ground-glass opacity area . 20% of the nodule and measured 2 cm in diameter, in 171 patients. We investigated the clinical characteristics and CT images of the subsolid nodules in relation to changes identified during the follow-up period. RESULTS: The nodule sizes ranged from 4 mm to 20 mm at the fi rst presentation. Nonsolid nodules numbered 98. During the follow-up period, 18 nodules showed resolution or shrinkage, and 41 showed growth of 2 mm or more in diameter. The time to 2-mm nodule-growth curves calculated by Kaplan-Meier methods indicated that the 2-year and 5-year cumulative percentages of growing nodules were 13% and 23% in patients with nonsolid nodules and 38% and 55% in patients with part-solid nodules, respectively. Multivariate analysis disclosed that a large nodule size ( . 10 mm) and history of lung cancer were significant predictive factors of growth in nonsolid nodules. CONCLUSIONS: An effective schedule for follow-up with CT scanning for subsolid nodules should be developed according to the type of subsolid nodule, initial nodule size, and history of lung cancer.

Late breast metastasis from resected lung cancer diagnosed by epidermal growth factor receptor gene mutation.

Primary lung cancer metastasizes to various organs, but rarely metastasizes to the breast. We report a case of breast metastasis from primary lung cancer, which was confirmed by the detection of the same epidermal growth factor receptor (EGFR) gene mutation.

High-density areas on muscle CT in childhood-onset Pompe disease are caused by excess calcium accumulation.

We report two patients with childhood-onset Pompe disease showing striking changes with high-density areas on skeletal muscle CT, not seen in adult- or infantile-onset forms of this disease. While the anterior compartment of the thigh muscles was less affected in the adult-onset form, the rectus femoris and tibial muscles were preferentially involved from the early stage in the childhood-onset form of Pompe disease. The high-density areas became increasingly diffuse with disease progression, producing a marbled pattern and ultimately resulting in homogeneous high density and muscle atrophy. Muscle biopsy specimens from the high-density areas showed striking vacuolar changes with many dense globular bodies in lysosomes. High calcium signals were identified by X-ray microanalysis using energy-dispersive X-ray spectroscopy in these areas. Excess calcium accumulation in the vacuoles was also confirmed with the glyoxal-bis(2-hydroxyanil) (GBHA) staining. The high density on CT was slightly reduced together with clinical improvement after enzyme replacement therapy in patient 2. Our data demonstrate that in childhood-onset Pompe disease, high-density areas on skeletal muscle CT images are due to the accumulation of calcium in dense globular bodies formed by a chronic degenerative process affecting autophagic vacuoles.

Transmanubrial osteomuscular sparing approach for lung cancer invading the anterior part of the thoracic inlet.

Standard treatment for lung cancer presenting as a superior sulcus tumor is induction chemoradiotherapy followed by surgery, which yields rates of about 70% complete resection and 50% 5-year survival rate. However, the surgical technique to achieve complete resection for superior sulcus tumor invading major anatomical sites including the subclavian artery is challenging. The anterior transcervical thoracic approach applied by Dartevelle and colleagues provides excellent exposure of the subclavian vessels. Grunenwald and associates have improved on this approach to preserve the clavicle and sternoclavicular joint. We applied the transmanubrial osteomuscular-sparing approach in two patients. In both cases, exposure of the subclavian vessels was excellent. In one case, the subclavian artery was resected and reconstructed with a polytetrafl uoroethylene graft. This patient has continued to show recurrence-free survival for more than 5 years. We outline our experience and review the literature on the surgical approach for superior sulcus tumor invading the anterior part of the thoracic inlet.

Can non-performance of radical systematic mediastinal lymphadenectomy be justified in elderly lung cancer patients? An evaluation using propensity-based survival analysis.

OBJECTIVES: The increasing age of the population has raised the importance of determining the minimally required surgical treatment for elderly lung cancer patients. Despite a number of previous studies, the therapeutic impact of a radical mediastinal lymphadenectomy (RLA) associated with a pulmonary resection for lung cancer remains controversial. Herein, we investigated the impact of lymph node dissection on the overall survival for elderly lung cancer patients and assessed whether the non-performance of an RLA could be justified in the surgical treatment for these elderly patients. METHODS: We analysed the data for 160 patients aged 70 years and older (113 males, 47 females) who underwent curative-intent surgery for non-small-cell lung cancer. They were divided into two groups, according to the method used for the intra-operative mediastinal lymph node dissection, the radical systematic lymphadenectomy (RLA, n=76) and the non-radical lymphadenectomy (NLA, n=94) groups. A Cox proportional hazards model and the Kaplan-Meier method were used for the survival analyses. Propensity-based analyses were also used to reduce the effect of non-randomisation and possible bias in indication of treatment between the two groups. RESULTS: RLAs had no protective effect on mortality; the hazard ratio for the RLA group in comparison to the NLA group was 0.97 (95% confidence interval (CI): 0.32-2.89) in the multivariate analysis and 1.43 (95% CI: 0.42-4.91) in the propensity-based stratifying analysis. The 3-year survival probability was 81.3% (95% CI: 67.1-89.8) for the NLA group, which was marginally better than that of the RLA group (77.5% (95% CI: 63.3-86.8)). There was no significant difference in the overall survival between the two groups (p=0.26). The 3-year survival probability of the NLA group at each quartile of the propensity score also tended to be better than that of the RLA group, which did not show any significant difference. CONCLUSIONS: There was no survival benefit shown for RLA associated with pulmonary resections in the present cohort, even in the propensity-based analyses. Although some reports recommend a systematic mediastinal lymphadenectomy for proper staging and better survival, a pulmonary resection with non-performance of radical lymphadenectomy could be an acceptable surgical treatment for the increasing number of elderly lung cancer patients.

Multimodality therapy for patients with invasive thymoma disseminated into the pleural cavity: the potential role of extrapleural pneumonectomy.

BACKGROUND: The optimal treatment method for thymoma with pleural dissemination remains controversial. We analyzed our experience with a multimodality approach and evaluated the role of extrapleural pneumonectomy (EPP) in the treatment of disseminated thymoma. METHODS: Multimodality therapy was used to treat 11 consecutive patients with invasive thymoma disseminated into the pleural cavity. Disease was stage IVa in 9 and stage IVb disease with lymph node metastasis in 2. Our treatment strategy for those patients was induction chemotherapy with cisplatin, doxorubicin, and methylprednisolone (CAMP therapy), followed by thymectomy combined with resection of the visible disseminated nodules and postoperative radiotherapy. EPP was applied for 4 patients who had chemoresistant tumors or pleural refractory recurrence. RESULTS: Eight patients underwent induction chemotherapy. The response rate to CAMP was 85%. Thymectomy with or without the resection of disseminated pleural tumors was performed in 7 patients and EPP in 3. Postoperative radiotherapy was administered in 6. All patients except 1 with EPP had recurrence: pleural recurrence in 7, lung in 1, and multiple organs in 2. Nine patients were retreated with chemotherapy, radiotherapy, pulmonary metastasectomy, or pleurectomy. One underwent EPP for pleural recurrence. Consequently, among the 7 patients without EPP, only 1 was alive without disease and 4 were alive with pleural recurrence. In contrast, 3 of the 4 patients with EPP had no local failure and were alive without recurrence. CONCLUSIONS: In multimodality therapy for thymoma with pleural dissemination, EPP offers good local control and may lead to cure.

[Treatment approach to congenital myasthenic syndrome in a patient with acetylcholine receptor deficiency].

Congenital myasthenic syndromes (CMS) are rare heterogeneous disorders of neurotransmission caused by genetic defects of neuromuscular junction molecules. While CMS patients have been reported worldwide, in Japan there have been only a few descriptions of adult CMS patients with acetylcholinesterase (AChE) deficiency and slow channel syndrome. Herein, we report a Japanese CMS patient with acetylcholine receptor (AChR) deficiency, diagnosed during childhood, and our treatment approach to the patient. This 13-year-old Japanese boy had had severe myasthenic symptoms since infancy. Ptosis, his first symptom, appeared at 5 months and nasal voice was recognized at 2 years of age. AchR and anti-muscle-specific tyrosine kinase (Musk) antibody remained negative. A positive tensilon test and decremental response on electromyogram supported the diagnosis of sero-negative myasthenia gravis. Despite thymectomy and strong immunosuppressive therapy including steroid pulse and FK 506, he gradually deteriorated and became wheelchair bound. Genetic analyses for AchR, Rapsyn, Musk and AChE were negative. At age 11 years, a muscle biopsy was performed in the deltoid muscle for neuromuscular junction sampling. Electron microscopic and confocal microscopic analysis of endplates showed almost complete loss of AChR and the diagnosis of CMS with AChR deficiency was confirmed. All immunosuppressive therapies were discontinued. Instead, we started Ubretide and 3,4-diaminopyridine (DAP) after obtaining informed consent. Although not approved in Japan for this use, 3,4-DAP is reportedly effective in refractory cases of CMS. The patient experienced no side effects. Despite all of the objective data were improving, his subjective symptoms and ADL remained poor. There are still many challenges in the treatment of the patient.

Benefits of FK 506 for refractory eye symptoms in a young child with ocular myasthenia gravis.

Recently, there have been many reports on the efficacy and safety of tacrolimus (FK506) treatment for adult patients with intractable generalized myasthenia gravis (MG). There have also been a few reports of successful FK506 therapy in patients with severe childhood-onset generalized MG involving a myasthenic crisis. Herein, we report the efficacy of FK 506 for refractory ocular symptoms in a 3-year-old girl with ocular type MG. Ptosis and alternating strabismus had appeared at 10 months of age. No bulbar signs, respiratory failure or generalized muscle weakness had been seen during her course. Her ocular symptoms had persisted despite repeated steroid pulse therapy, high dose oral prednisolone and thymectomy. Adverse effects of steroids, including obesity, growth retardation, osteoporosis, cataracts and hyperlipidemia, gradually worsened. After obtaining written informed consent from her parents, we started oral tacrolimus at a dose of 0.5mg/day and her symptoms resolved completely within 3 weeks at a maximum dose of 2.5mg/day. No adverse effects, such as renal failure or glucose intolerance, were seen. FK506 treatment allowed the steroid dose to be reduced, eliminating its adverse effects. In patients with intractable childhood-onset MG with ocular manifestations, FK506 is an alternative to steroid therapy or thymectomy.

Postoperative radiotherapy for patients with completely resected pathological stage IIIA-N2 non-small cell lung cancer: focusing on an effect of the number of mediastinal lymph node stations involved.

Postoperative radiotherapy (PORT), especially using modern technology, for patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. We retrospectively investigated 112 patients with stage IIIA-N2 NSCLC who underwent complete resection of the lung tumor in our institution from 1986 through 2003. Among the 91 patients determined suitable candidates for PORT postoperatively, 45 patients received PORT (PORT group) and 46 did not (non-PORT group). We analyzed the correlation between PORT use and clinicopathological characteristics, number of involved mediastinal lymph node stations, recurrence, and survival. Five-year and 10-year survival rates of PORT group were 53.2% and 40.0%, which were superior, however, not statistically different, to those (39.3% and 27.5%) of non-PORT group (P=0.6284). According to the number of mediastinal lymph node stations, PORT was more effective for multiple station metastasis than single station metastasis. The disease-free survival of PORT group was significantly better than that of non-PORT group among the patients with multiple station metastasis. Five-year disease-free survival rate of PORT group and non-PORT group were 41% and 5.9%, respectively (P=0.0220). PORT using modern techniques can reduce local recurrence and improve overall survival especially for patients with multiple station N2. Prospective randomized control trials are warranted.

Pathologic stage I non-small cell lung cancer with high levels of preoperative serum carcinoembryonic antigen: clinicopathologic characteristics and prognosis.

OBJECTIVE: Surgery alone remains the standard therapy for patients with stage I non-small cell lung cancer. Although the preoperative serum level of carcinoembryonic antigen has been shown to be an independent prognostic factor, it has not yet been included in the staging system and does not alter the treatment strategy, especially in the selection of patients for adjuvant chemotherapy. METHODS: From 1986 to 2003, preoperative and postoperative serum carcinoembryonic antigen levels were measured in 455 patients with completely resected pathologic stage I non-small cell lung cancer. We compared the clinicopathologic characteristics and outcomes among patients who had preoperative serum carcinoembryonic antigen levels within the normal range (N group, n = 323), patients who had high carcinoembryonic antigen levels before surgery but normal levels after surgery (HN group, n = 112), and patients who had high carcinoembryonic antigen levels before and after surgery (HH group, n = 20). RESULTS: The significant characteristics of the HN group included the male sex, greater age, smoking, squamous cell histology, T2 status, lymphatic invasion, vascular invasion, and pleural invasion. Adenocarcinomas in patients of the HN group were more likely to be moderately to poorly differentiated. The 5-year survivals in the HN and HH groups were significantly lower (56.2% and 43.1%, respectively) than those in the N group (85.9%). Multivariate analysis revealed that greater age, non-adenocarcinoma histology, pleural invasion, and the carcinoembryonic antigen in the HN and HH groups were independent prognostic factors. CONCLUSION: Patients with resected pathologic stage I non-small cell lung cancer and high preoperative serum carcinoembryonic antigen levels are a subgroup with a distinctly poor prognosis who display smoking-related clinicopathologic characteristics.

Desmoid tumor presenting as a superior sulcus tumor: a unique bone change in the vertebral body.

Desmoid tumor, also referred to as aggressive fibromatosis, is a relatively rare, locally infiltrative, histologically benign tumor. This report details a case of desmoid tumor presented as a superior sulcus tumor, which showed a unique manifestation in the vertebral bodies on computed tomography.

Head and neck metastases from occult abdominal primary site: a case report and literature review.

OBJECTIVES: A very rare case of cervical lymph node metastasis from the liver is reported. The clinical findings and the diagnosis of a metastasis to the head and neck from the isolated silent abdominal cancer are discussed. MATERIAL AND METHODS: The clinical and histopathological findings of a 56-year-old woman with a metastatic cervical lymph node of unknown origin are presented, together with a literature review of metastases from an occult abdominal primary. RESULTS: The primary site was identified as an undifferentiated cholangiolocellular carcinoma using immunostaining for anti-cytokeratin subclasses after autopsy. Fifty-two cases of head and neck metastases from an abdominal primary cancer were found and separately summarized according to the metastatic routes. CONCLUSIONS: When a metastatic neck cancer of unknown origin is diagnosed, it is very important to consider the possibility of a metastasis from an abdominal organ. Recognition of metastatic routes and their characteristics is helpful in the search for the occult abdominal primary site. Immunohistochemistry of the metastatic cancer may provide important information for identifying the primary site in cases of metastasis of an undifferentiated carcinoma.

[A two-year-old infant with a myopathic form of very-long-chain Acyl-CoA dehydrogenase deficiency].

A two-year-three-month old girl was hospitalized for detailed examination following repeated hyper-creatine kinasemia and cervical muscle cramps induced by pyrexia and persistent hypertonicity of the cervical muscles. Physical examination showed mild hypotonia but no muscle weakness. Induction of symptoms by continuous cervical muscular exercise and the appearance of dicarboxylic aciduria during the fasting test indicated a disorder of fatty acid oxidation. Free fatty acid and acyl carnitine analyses using dried blood spots, and acyl-CoA dehydrogenase activity assays using cultured skin fibroblasts established a diagnosis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Currently VLCAD deficiency has been divided into three phenotypes; a severe childhood form, a milder childhood form, and an adult form. However, we suggest that the severe and milder childhood forms would be better described as a systemic form, and the adult form and our infant case as a myopathic form. An early onset of the myopathic form within the first year of life, as well as its diagnosis in early infancy, has never been described in the literature.