Gradual and Remarkable Tumor Shrinkage Following Seven-Fraction Stereotactic Radiosurgery Alone With a Marginal Dose of 48.3 Gy for Large Lobar Possibly Intra-sulcal Brain Metastasis From Renal Cell Carcinoma.

Brain metastases (BMs) from renal cell carcinoma (RCC) have the tendency of slow and insufficient tumor shrinkage along with prolongation of massive peritumoral edema following stereotactic radiosurgery (SRS). Herein, we describe a case of large lobar RCC-BM, with possible intra-sulcal location, treated with 7-fraction (fr) SRS without subsequent anti-cancer medication, which resulted in gradual and remarkable tumor shrinkage with extrication from the mass effect. A 59-year-old woman was incidentally diagnosed with bilateral RCC associated with multiple lung metastases and subsequently presented with symptomatic single BM of 32 mm in the maximum diameter (9.54 cm3) two months later while vacillating. A biopsy of the kidney showed clear cell carcinoma. The patient was deemed medically inoperable for BM due to unfit conditions, including severe deep venous thromboses and thrombocytopenia. Considering the tumor volume, irregular tumor configuration, non-superficial location, and mass effect, 98% of the gross tumor volume (GTV D98%) was covered by 48.3 Gy in 7 fr with 64% isodose. Dose distribution was optimized with volumetric modulated arcs with the affirmative allowance of very inhomogeneous GTV dose. Anti-cancer medication was limited to nivolumab plus ipilimumab followed by everolismus 12 days before and during SRS, respectively. Subsequently, the patient transitioned to palliative care due to a declining general condition. Although long-term administration of steroids was required, gradual and marked tumor shrinkage (1.25 cm3, 13.1% of the initial volume) and mitigation of the peritumoral edema was observed during six months after SRS. The main location of the initial BM was deemed as intra-sulcal in the intraparietal sulcus and originated in the cerebral cortex. The patient died nine months after SRS. The gradual but remarkable tumor response obtained with 7-fr SRS alone, in this case, provides a basis to further optimize fractionated SRS dosage to enhance efficacy and safety for large and/or symptomatic RCC-BMs not amenable to immediate surgical removal, in combination with anti-cancer pharmacotherapy, if feasible, including tyrosine kinase inhibitors, which may enhance efficacy against BM and mitigate adverse effects relevant to high dose SRS.

[CLINICAL INVESTIGATION OF TUBERCULOSIS PATIENTS IN A GENERAL HOSPITAL LACKING A TUBERCULOSIS WARD IN WESTERN AICHI PREFECTURE.]

With the recent decrease in the number of tuberculosis wards and increase in elderly tuber- culosis patients with comorbidities, the role of regional refer- ral hospitals has become more important in tuberculosis management. [Objective]. This study aimed to assess the current state of tuberculosis management and related issues in a general hospital lacking a tuberculosis ward. [Methods] We retrospectively evaluated the clinical char- acteristics and course of patients diagnosed with tuberculosis by culture testing from April 2008 to March 2015 at Kainan Hospital. [Results] A total of 146 patients (83 males and 63 females; mean age 76, range 18-94 years) were diagnosed with active tuberculosis. Of these, 129 were diagnosed with pulmonary tuberculosis (23 had pulmonary tuberculosis with pleurisy), and 17 patients were diagnosed with extrapulmonary tuber- culosis. The chief complains were cough/sputum in 40 cases, fever in 24, and no symptoms in 36. Associated major comorbidities included diabetes mellitus, chronic kidney disease, and malignancy. In 33 patients, over 30 days were required to diagnose tuberculosis after initial evaluation. Drug-resistant strains were detected in 14 patients. 57 were diagnosed with smear-positive pulmonary tuberculosis, and 66 were transferred to a tuberculosis hospital. Modify in anti- tuberculosis therapy due to adverse reactions were reported in 27 patients. [Conclusion] This study evaluated the current state of tuberculosis management in our hospital. Further educational guidance regarding tuberculosis is needed for the hospital staff, and is important for improvement of tuberculosis management in our hospital.

[DISSEMINATED MYCOBACTERIUM INTRACELLULARE INFECTION IN A PATIENT WITH MYELODYSPLASTIC SYNDROME].

A 71-year-old man with myelodysplastic syndrome (MDS) was admitted to our hospital because of recurrent high-grade fever. He was examined for bacterial and fungal infections and treated with antibiotics and antifungal agents. However, he did not achieve a definitive diagnosis and had no apparent improvement for more than a month. Bone marrow aspiration revealed transformation of MDS to acute myeloid leukemia and hemophagocytosis. In addition, Mycobacterium intracellulare was isolated from both a bone marrow specimen and a blood sample. Therefore, he was diagnosed with disseminated Mycobacterium avium complex (MAC) infection with hemophagocytosis. An antibody test was negative for human immunodeficiency virus (HIV). His general condition improved with anti-mycobacterial drug and steroid treatments. Clinicians should suspect disseminated nontuberculous mycobacterial infections in unexplained febrile patients with hematological disorders.

Epidermal growth factor receptor-tyrosine kinase inhibitors for non-small-cell lung cancer patients aged 80 years or older: A retrospective analysis.

The efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in elderly patients with non-small-cell lung cancer (NSCLC) remains uncertain. This retrospective study aimed to evaluate the efficacy and feasibility of EGFR-TKIs for NSCLC patients aged ≥ 80 years. We analyzed data from 21 NSCLC patients aged ≥ 80 years who were administered gefitinib and/or erlotinib between January, 2009 and December, 2014. The clinical characteristics, smoking status, type of EFGR mutation and the efficacy and toxicity of EGFR-TKIs were evaluated in these patients. In total, 14 (66.7%), 5 (23.8%) and 2 patients (9.5%) displayed partial response, stable disease and progressive disease, respectively. The median progression-free survival was 182 days, whereas the median overall survival was 371 days. Adverse events ≥ grade 2 were as follows: skin toxicities, 12 patients; liver function test abnormalities, 7 patients; anorexia, 3 patients; and diarrhea, 2 patients. Dose reduction of EGFR-TKIs due to adverse events was required in 15 patients (71.4%). Although gefitinib and erlotinib therapy may be beneficial in patients aged ≥ 80 years, EGFR-TKI dose modification may be necessary according to the overall medical condition of elderly patients. Further studies are required to evaluate our findings.

[A case of multiple myeloma in a young adult, discovered on the basis of an abnormal finding on a chest X-ray film].

A 35-year-old woman was referred to our hospital because of an abnormal finding on a chest X-ray film. Chest and abdominal computed tomography (CT) revealed a 25 × 5-mm tumor in the anterior right third rib as well as punched-out lesions in the vertebral bodies and iliac bones. Positron emission tomography (PET)/CT revealed accumulation in the right third rib and lumbar vertebral bodies. From these imaging findings and the lumbar magnetic resonance imaging (MRI) findings, we suspected a case of multiple myeloma. We performed histological bone marrow examination, serum protein electrophoresis, and urine immunoelectrophoresis. The patient was finally diagnosed with a Bence-Jones-type multiple myeloma. To our knowledge, this is a rare case of multiple myeloma in a young adult, discovered on the basis of an abnormal finding on a chest X-ray film.

Planer orientation of the bilateral semicircular canals in dizzy patients.

OBJECTIVE: Recent development of 3-dimensional analysis of eye movement enabled to detect the eye rotation axis, which is used to determine the responsible semicircular canal(s) in dizzy patients. Therefore, the knowledge of anatomical orientation of bilateral semicircular canals is essential, as all 6 canals influence the eye movements. SUBJECTS AND METHODS: Employing the new head coordinate system suitable for MR imaging, we calculated the angles of semicircular canal planes of both ears in 11 dizzy patients who had normal caloric response in both ears. RESULTS: The angles between adjacent canal pairs were nearly perpendicular in both ears. The angle between the posterior canal planes and head sagittal plane was 51° and significantly larger the angle between the anterior canal planes and head sagittal plane, which was 35°. The angle between the horizontal canal plane and head sagittal plane was almost orthogonal. Pairs of contralateral synergistic canal planes were not parallel, forming 10° between right and left horizontal canal planes, 17° between right anterior and left posterior canal planes and 19° between the right posterior and left anterior canal planes. CONCLUSION: Our measurement of the angles of adjacent canal pairs and the angle between each semicircular canal and head sagittal plane coincided with those of previous reports obtained from CT images and skull specimens. However, the angles between contralateral synergistic canal planes were more parallel than those of previous reports.

A new coordinates system for cranial organs using magnetic resonance imaging.

CONCLUSION: We developed a new coordinates system for magnetic resonance imaging (MRI) that utilizes the labyrinth and eyeballs as references to measure the spatial arrangement of cranial organs, and we verified its usefulness by observing small structures in the labyrinth in 39 ears from 33 patients. Our new coordinates system could be used for stereotactic analysis of cranial organs in MRI. OBJECTIVES: To research semicircular canal anatomy in healthy organisms, we propose a method that employs references visible on MRI for stereotactic measurement of cranial structures, and we evaluated the usefulness of our method. METHODS: Using the new coordinates system and vector analysis, we calculated angles among the semicircular canals and sagittal head plane from MRI volume data containing temporal bone and orbit. RESULTS: The angle between the anterior semicircular canal plane and sagittal plane was 35.3 +/- 4.1 degrees; posterior semicircular canal plane and sagittal plane, 50.9 +/- 4.7 degrees; and horizontal semicircular canal plane and sagittal plane, 90.4 +/- 7.0 degrees. The angle between the anterior and posterior semicircular canal planes was 95.1 +/- 4.2 degrees; anterior and horizontal semicircular canal planes, 92.3 +/- 7.5 degrees; and posterior and horizontal semicircular canal planes, 93.5 +/- 4.9 degrees.

A head-tilt caloric test for evaluating the vertical semicircular canal function.

CONCLUSIONS: The caloric test with head-tilt can be used as a tool for assessing vertical canal function as an office procedure. OBJECTIVE: Evaluation of vertical canal function. PATIENTS AND METHODS: We provoked caloric response by cold water in the vertiginous patients in supine position. During the culmination of the response we rotated the head 45 degrees from the sagittal plane to place the posterior canal to earth-vertical. Thereafter we rotated the head 45 degrees to the opposite direction to place the anterior canal to earth-vertical. The eye movements were recorded by two-dimensional electronystagmography. The data collected from the examination of 100 ears with normal caloric response in horizontal component were analyzed. RESULTS: The down-beating vertical component intensified when the posterior canal was placed to earth-vertical. The up-beating vertical component intensified when the anterior canal was placed to earth-vertical. These findings suggested that the vertical canals were functioning.

[Acute pancreatitis associated with the administration of ceftriaxone in an adult patient].

We report a case of a 35-year-old patient with acute pancreatitis after administration of ceftriaxone. She was given ceftriaxone (2g/day) for 9 days because of diverticulitis of the colon. She was admitted to our hospital again because of epigastralgia 12 days after the first administration of ceftriaxone. Laboratory examination showed markedly elevated serum amylase, and CT scan demonstrated findings consistent with acute pancreatitis, in addition to sludge in the common bile duct and gall bladder, which was not identified before the administration of ceftriaxone. We should be aware of the fact that administration of ceftriaxone sometimes results in the formation of biliary sludge and can cause severe adverse events such as cholecystitis and pancreatitis, not only in children, but also in adult patients.

An effective maneuver of positional test by turning of the head and body together.

OBJECTIVE: To find the effective maneuver of a positional test. METHODS: We performed three different maneuvers of a positional test in 86 vertiginous patients in supine-lying position in the following order: (1) "body-only maneuver": a patient turned only his body to one side while keeping his head still; (2) "head-only maneuver": a patient turned only his head to one side while keeping the body still; (3) "head-and-body maneuver": a patient turned his head and body together to one side. Eye movement during the whole procedure was recorded by two-dimensional electronystagmography. RESULTS: Nystagmus provocation rates were 9% in "body-only maneuver", 16% in "head-only maneuver", and 33% in "head-and-body maneuver". CONCLUSION: The positional test in which patient turned his head and body together proved most effective.

Clinical significance of vertical component of caloric response including its second phase in vertiginous patients.

CONCLUSIONS: Up-beating vertical component recorded in the caloric first phase was attributed mainly to the inhibitory endolymph flow in the anterior canal. Down-beating vertical component recorded in the caloric second phase provoked by a positional change could be explained by a reversed endolymph flow in vertical canal(s). OBJECTIVE: To investigate the origin of a vertical component in caloric response. MATERIALS AND METHODS: We analyzed electronystagmography (ENG) of caloric responses, which had measurable horizontal component in the caloric first phase in both ears in 200 ears of 100 vertiginous patients. A caloric first phase was provoked by cold water in the supine position with the lateral semicircular canal earth-vertical. A caloric second phase was provoked by re-orienting the lateral canal from the earth-vertical to earth-horizontal after the cessation of the first phase (provoked second phase). The nystagmus of the whole procedure was recorded by two-dimensional ENG. RESULTS: We recorded the vertical component in 103/200 ears in the caloric first phase, which was directed mostly upward (92/103 ears). We also recorded the vertical component in 91/200 ears in the provoked second phase, which was directed almost exclusively downward (90/91 ears).

Effective maneuver of the positional test: turning head and body together.

We performed three maneuvers of the positional test in supine patients: (1) body maneuver, in which patients turned only the body to one side while keeping the head as still as possible; (2) head-only maneuver, in which patients turned only the head to one side while keeping the body still; and (3) head and body maneuver, in which patients turned the head and body together to one side. The nystagmus provocation rates of those three maneuvers among 86 vertiginous patients were 9% in the body maneuver, 16% in the head-only maneuver, and 33% in the head and body maneuver, respectively. We proved that performing the positional test by turning the head and body together is very effective in provoking positional nystagmus.

Monocular electronystagmographic analysis of caloric nystagmus.

We compared the horizontal component of nystagmus of the right and left eyes using monocular recording of electronystagmography. We examined the eye movements of 135 patients during bithermal caloric testing and those of 50 patients during the rotation test. We measured the number of nystagmic beats, the slow-phase velocities, and the amplitudes during 10 seconds of the culmination phase of caloric response. We also measured the number of nystagmic beats during the first 30 seconds in postrotatory nystagmus. The eye on the cold-irrigated side moved significantly more strongly than did the eye on the nonirrigated side, whereas a warm irrigation did not induce a significant difference between the irrigated and nonirrigated eyes. The summated activities of each eye during the four different stimulations under bithermal caloric testing did not show any significant differences. The activities of postrotatory nystagmus were almost equal in both eyes in 50 patients. We concluded that the inhibitory effect of cold caloric stimulation is probably transmitted more intensively to the eye on the irrigated side.

Vertical component of the caloric response, including a caloric second phase provoked by positional change: a preliminary report.

We measured the horizontal and vertical components of caloric nystagmus in 120 ears of 60 vertiginous patients who had moderate to vigorous caloric first-phase response in both ears, no spontaneous nystagmus, and no severe disorders in the central nervous system. We provoked a caloric first phase in the supine position with 5 ml of water at 20 degrees C for 15 seconds. We provoked a caloric second phase by changing the position of a patient from supine to sitting after the end of the first phase. The horizontal component of the caloric second phase was recorded in 108 of 120 ears (90%). The vertical component was recorded in 57 of 120 ears (48%) during the caloric first phase and in 51 of 120 ears (43%) during the caloric second phase. We suspected that the vertical component of the caloric first phase was mainly due to the inhibition of the anterior semicircular canal.

The clinical significance of the caloric second phase provoked by positional change in vertiginous patients.

The reversal phase of caloric nystagmus is provoked when the lateral semicircular canal in a patient is reoriented from a vertical to a horizontal plane at the cessation of the caloric first phase, which we called the provoked caloric second phase. In investigating the clinical significance of the provoked caloric second phase, we recruited 102 vertiginous patients who had measurable caloric responses in both ears but no disorders of the central nervous system. We recorded the provoked caloric second phase in 188 (92%) of 204 ears in 102 patients. The average maximum slow-phase velocity of the caloric first phase was 26.9 degrees per second, and that of the provoked caloric second phase was 5.0 degrees per second. The maximum slow-phase velocity of the provoked caloric second phase correlated with that of the foregoing caloric first phase (r = -.84). Thus, we consider that the provoked caloric second phase is influenced largely by the foregoing caloric first phase. Furthermore, in the patients who responded normally to caloric stimulation, the directional preponderance of the provoked caloric second phase correlated with the directional preponderance of optokinetic after-nystagmus (r = .64). Hence, we conclude that the provoked caloric second phase reflects central vestibular asymmetry in patients with normal peripheral vestibular function.