Prognostic Accuracy of the qSOFA Score for In-Hospital Mortality in Elderly Patients with Obstructive Acute Pyelonephritis: A Multi-Institutional Study.

Prognostic accuracy of the quick sequential organ failure assessment (qSOFA) score for mortality may be limited in elderly patients. Using our multi-institutional database, we classified obstructive acute pyelonephritis (OAPN) patients into young and elderly groups, and evaluated predictive performance of the qSOFA score for in-hospital mortality. qSOFA score ≥ 2 was an independent predictor for in-hospital mortality, as was higher age, and Charlson comorbidity index (CCI) ≥ 2. In young patients, the area under the curve (AUC) of the qSOFA score for in-hospital mortality was 0.85, whereas it was 0.61 in elderly patients. The sensitivity and specificity of qSOFA score ≥ 2 for in-hospital mortality was 80% and 80% in young patients, and 50% and 68% in elderly patients, respectively. For elderly patients, we developed the CCI-incorporated qSOFA score, which showed higher prognostic accuracy compared with the qSOFA score (AUC, 0.66 vs. 0.61, p < 0.001). Therefore, the prognostic accuracy of the qSOFA score for in-hospital mortality was high in young OAPN patients, but modest in elderly patients. Although it can work as a screening tool to determine therapeutic management in young patients, for elderly patients, the presence of comorbidities should be considered at the initial assessment.

Clinical response to sodium glucose co-transporter 2 inhibitor ipragliflozin in a patient with metastatic renal cell carcinoma.

INTRODUCTION: Sodium glucose co-transporter 2 inhibitors constitute a new class of antidiabetic medication. Sodium glucose co-transporter 2 inhibitors have been shown to exert anticancer effects. However, the clinical value of these drugs as anticancer agents is yet to be evaluated. CASE PRESENTATION: A 72-year-old man presented to our hospital with frequent cough and dyspnea. Contrast-enhanced computed tomography revealed renal cell carcinoma cT3bN0M1. Ipragliflozin, a sodium glucose co-transporter 2 inhibitor, treatment was initiated to control blood glucose levels. Two years after diagnosis, computed tomography revealed remarkable tumor regression without any systemic therapy other than ipragliflozin. CONCLUSION: Sodium glucose co-transporter 2 inhibitors are potentially applicable as anticancer agents among patients with metastatic renal cell carcinoma.

Blood pressure fluctuation and hypertension in patients with Parkinson's disease.

OBJECTIVES: Blood pressure (BP) abnormalities have been known in Parkinson's disease (PD) patients. The present study aimed at determining how the BPs of PD patients fluctuate in a day. METHODS: A total of 37 PD patients and 44 OD (other disease) patients, all of who were inpatients, were monitored every 30 min by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: The average systolic BP and the number of patients who showed postprandial hypotension were not different between the two groups. However, occurrence of nocturnal hypertension, BP fluctuation of over 100 mmHg in a day and BP of over 200 mmHg were significantly more frequently observed in the PD patients than in the OD patients. In the PD patients, these parameters were not different between those who were suffering from the disease for less than 10 years and those with the disease for 10 years or longer, as well as between those who had a Hoehn-Yahr staging scale of 2-3 and those with a scale of 4-5. CONCLUSION: Twenty-four-hour ABPM, not BP measurement once a day, enables us to determine the actual BP in PD patients. Although hypotension is a severe risk factor for falling and syncope, we emphasize the importance of monitoring rather hypertension and fluctuating BP in PD patients that may lead to a variety of other undesirable conditions. Management of hypotension, hypertension, and BP fluctuation is an important issue in the future.

Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS.

BACKGROUND: Mutations in the microtubule associated protein tau (MAPT) and progranulin (PGRN) have been identified in several neurodegenerative disorders, such as frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). Recently, C9orf72 repeat expansion was reported to cause FTLD and amyotrophic lateral sclerosis (ALS). To date, no comprehensive analyses of mutations in these three genes have been performed in Asian populations. The aim of this study was to investigate the genetic and clinical features of Japanese patients with MAPT, PGRN, or C9orf72 mutations. METHODS: MAPT and PGRN were analyzed by direct sequencing and gene dosage assays, and C9orf72 repeat expansion was analyzed by repeat-primed PCR in 75 (48 familial, 27 sporadic) Japanese patients with FTLD, PSP, or CBS. RESULTS: We found four MAPT mutations in six families, one novel PGRN deletion/insertion, and no repeat expansion in C9orf72. Intriguingly, we identified a de novo MAPT p.S285R mutation. All six patients with early-onset PSP and the abnormal eye movements that are not typical of sporadic PSP had MAPT mutations. The gene dosages of MAPT and PGRN were normal. DISCUSSION: MAPT p.S285R is the first reported de novo mutation in a sporadic adult-onset patient. MAPT mutation analysis is recommended in both familial and sporadic patients, especially in early-onset PSP patients with these abnormal eye movements. Although PGRN and C9orf72 mutations were rare in this study, the PGRN mutation was found in this Asian FTLD. These genes should be studied further to improve the clinicogenetic diagnoses of FTLD, PSP, and CBS.

[A case of metastatic paratesticular rhabdomyosarcoma in an adult successfully treated with multidrug combination chemotherapy].

A 20-year-old man was referred to our hospital with the complaint of a mass in the left scrotum. Computed tomography showed retroperitoneal lymph node metastases and multiple lung metastases. He underwent left high orchiectomy and was diagnosed with paratesticular embryonal rhabdomyosarcoma. He received combination chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin, and dacarbazine. After four cycles of chemotherapy, lung metastases disappeared and lymph nodes decreased dramatically. He was alive without recurrence 31 months after the operation.

Feasibility of antegrade radical prostatectomy for clinically locally advanced prostate cancer: a comparative study with clinically localized disease.

OBJECTIVES: To investigate intraoperative and early postoperative complications of antegrade radical prostatectomy with intended wide resection (aRP) for clinically locally advanced prostate cancer (cLAD) and to compare with those of aRP for clinically localized prostate cancer (cLD). METHODS: Between March 1994 and June 2007, 800 consecutive Japanese patients including 625 with cLD and 175 with cLAD underwent aRP and bilateral limited lymphadenectomy. Clinicopathological data including intraoperative and early postoperative complications (within 30 days after operation) were compared between cLD and cLAD groups. RESULTS: No deaths occurred. Operative time and blood loss did not differ significantly between the groups. Intraoperative and early postoperative complications were observed in 11 (1.4%) and 123 (15.4%) of the entire cohort, respectively. Prevalent early postoperative complications were pelvic hematoma, wound infection, urinary retention and lymphocele or prolonged lymph drainage. There were no significant differences in the entire intraoperative and early postoperative complications between the groups. The majority of the early postoperative complications were minor. CONCLUSIONS: aRP for cLAD is technically feasible and a safe surgical procedure. If radical prostatectomy could be established as a standard treatment for cLAD in the future, aRP might be valuable as the first step of multimodal treatments.

Risk stratification of high-grade prostate cancer treated with antegrade radical prostatectomy with intended wide resection.

OBJECTIVE: The aim of this study was to assess the surgical outcome of high-grade prostate cancer (PCA) treated with antegrade radical prostatectomy with intended wide resection (aRP) and to establish the risk stratification. METHODS: A consecutive 77 Japanese patients with Gleason score 8-10 PCA were treated with aRP alone and excluding patients with persistently elevated prostate-specific antigen (PSA), prospectively observed without any treatment until PSA failure was confirmed. PSA failure-free, cancer-specific and overall survival curves were generated with Kaplan-Meier method and the difference between groups was assessed with log-rank test. Cox's proportional hazards model was used to elucidate predictors of PSA failure. RESULTS: During a median follow-up of 6 years, PSA failure was observed in 41 (53%) of the 77 patients. Five- and 10-year PSA failure-free survival rates of the entire cohort were 44.6% and 40.1%, respectively. Both overall and cancer-specific survival rates of the entire cohort at 5 and 10 years were 96.8% and 87.9%, respectively. In a multivariate analysis, PSA (P = 0.008), specimen confinement (SC) (P = 0.006) and persistently elevated PSA after aRP were identified as significant and independent predictors of PSA failure. When stratifying patients into three risk groups according to PSA level and SC status, PSA failure-free survival rate in patients with PSA < 10 ng/ml and specimen-confined disease (SCD) was significantly better than that in those of any other groups. CONCLUSIONS: Good prognosis can be expected in patients with high-grade PCA treated with aRP alone when PSA < 10 ng/ml and the tumor was removed as an SCD.

Prognostic significance of cancer volume involving seminal vesicles in patients with pT3bpN0 prostate cancer.

OBJECTIVES: To investigate the prognostic effect of the prostate cancer (PCa) volume involving the seminal vesicles (CVSVs) in the radical prostatectomy specimen from patients with Stage pT3bpN0 PCa. METHODS: We retrospectively reviewed the clinical records of 27 patients with Stage pT3bpN0 PCa who had undergone radical prostatectomy alone. We measured the CVSVs using a grid method on the glass slide under microscopic inspection and investigated the association of the CVSVs with clinicopathologic variables. RESULTS: Prostate-specific antigen (PSA) failure was confirmed in 11 of the 27 patients (41%) during a median follow-up of 34 months. The 3-year PSA failure-free survival rate was 48%. The median CVSVs was 1.14 cm(3). On univariate analysis, a CVSVs of >1.63 cm(3) was associated with positive surgical margins (P = .018), bilateral seminal vesicle involvement (P = .03), a long maximal tumor dimension (P = .031), and a greater preoperative PSA level (P = .0007). The 3-year PSA failure-free survival rate for those with a CVSVs of 1.63 cm(3) was 80% and 0%, respectively (P = .0009). On multivariate analysis, only the PSA level and CVSVs were identified as significant and independent predictors of PSA failure. Stratifying patients into 3 risk groups by these predictors, the PSA failure-free survival rate for patients with a PSA level >or=10 ng/mL and a CVSVs of >1.63 cm(3) was significantly worse than for any other group. CONCLUSIONS: The CVSVs is useful and invaluable as an independent predictor of PSA failure in patients with Stage pT3bpN0 PCa. The measurement of the CVSVs is simple and helped to determine the indication for adjuvant treatment after radical prostatectomy.

Simultaneously cooperative, but serially antagonistic: a neuropsychological study of diagonistic dyspraxia in a case of Marchiafava-Bignami disease.

We describe a patient with Marchiafava-Bignami disease who showed, in addition to signs of callosal interruption, a peculiar form of diagonistic dyspraxia. Unlike the typical diagonistic dyspraxia, both of the patient's hands could simultaneously cooperate in a sequence of bimanual actions. More specifically, his right hand could start a commanded action with the cooperation of his left hand. However, once the action was completed, his left hand started an antagonistic action, undoing the result, with the cooperation of his right hand. Once this countermanding action was completed, the original action started again. These antagonistic actions repeated themselves alternately unless he was restrained. The patient's diagonistic dyspraxia was apparent in only some bimanual actions, and he showed no diagonistic dyspraxia when performing voluntary actions; the antagonistic actions occurred in response to oral commands or by imitation. Magnetic resonance imaging showed symmetrical demyelination with partial necrosis in the genu, body, and anterior splenium of the corpus callosum. We speculate that the bimanual coordination is possible because part of the corpus callosum is intact, whereas the antagonistic actions may be caused by conflict between the two hemispheres due to interhemispheric disinhibition elicited by the demyelinated part of the corpus callosum.

[Estramustine phosphate withdrawal syndrome in relapsed prostate cancer: two case reports].

The decrease of the level of serum prostate specific antigen (PSA) after discontinuation of estramustine phosphate (EMP) has rarely been reported. We report 2 cases in whom EMP withdrawal syndrome was encountered. Case 1 was a 68-year-old man with a complaint of paresis of lower limbs. He was diagnosed with prostate cancer with multiple bone metastases. The serum PSA level was 9,300 ng/ml. He was treated with luteinizing hormone-releasing hormone agonist (LH-RHa) and bicalutamide (BCL). Six months later, EMP was started against PSA failure. During the 3-year treatment with EMP, PSA decreased to the nadir of 0.7 ng/ml and gradually increased to 14 ng/ml. After withdrawal of EMP, PSA decreased to 0.3 ng/ml (97.9% decline) and remained at this level for 4 months. Case 2 was a 61-year-old man who visited our hospital with gross hematuria. Transurethral bladder biopsy and transrectal prostate biopsy were performed. The diagnosis was moderately differentiated adenocarcinoma of the prostate that invaded to the bladder. Computed tomography (CT) showed a lymph node metastasis. He was treated with LH-RHa and BCL. The treatment was changed to EMP after PSA failure. EMP was withdrawn when PSA was 30 ng/ml. Then PSA decreased to less than 0.2 ng/ml (99% decline) and remained at this level for 9 months. We consider that in patients with EMP-resistant progression, EMP withdrawal syndrome should be checked.

[A case of adenocarcinoma of the urinary bladder arising 45 years after ileal replacement of ureter for tuberculous ureteral stricture].

We report a case of adenocarcinoma arising in the urinary bladder 45 years after ileal replacement of ureter for tuberculous ureteral stricture. A 65-year-old man was admitted with gross hematuria. Cystoscopic examination demonstrated a broadbased non-papillary tumor on the left posterior wall of the bladder and a papillary tumor at the anastomotic site between the bladder and ileal segment. Total cystectomy and construction of ileal conduit were performed. The histopathological examination demonstrated well differentiated adenocarcinoma of the bladder and ileal ureter. Intestinal metaplasia widely infiltrated into the bladder epithelium around the anastomotic site.

Superior vena cava syndrome caused by supraclavicular lymph node metastasis of renal cell carcinoma.

A 65-year-old woman presented with gross hematuria in February 1997. Left renal tumor was revealed and radical nephrectomy was performed. Pathological examination revealed papillary renal cell carcinoma, pT3aN1M1 (ipsilateral adrenal gland). Interferon-alpha was administered for 1 year. Two years after the nephrectomy, metastasis to the left supraclavicular lymph node appeared. Seven years after the nephrectomy, the metastatic tumor invaded the brachiocephalic vein and extended to the superior vena cava (SVC), compatible with SVC syndrome. Although interferon-alpha and external-beam radiotherapy was performed, she died in February 2005. Autopsy revealed a left supraclavicular lymph node metastasis invading the thyroid gland, mediastinum, and brachiocephalic vein. The tumor thrombus descended via the SVC into the right atrium. The right lung artery was obstructed by tumor thrombus. There were no visceral metastases and no local recurrence.

Antegrade radical retropubic prostatectomy with preliminary ligation of vascular pedicles in 614 consecutive patients.

BACKGROUND: We present our procedure of antegrade radical retropubic prostatectomy with preliminary ligation of vascular pedicles and assess the time trends of patient characteristics, surgical and oncological outcome in 614 consecutive patients in a single institution over a 12-year period. METHODS: From April 1994 to December 2005, 614 consecutive Japanese patients with cT1-3N0M0 prostate cancer underwent antegrade radical prostatectomy with preliminary ligation of vascular pedicles (dorsal vein complex and prostatic pedicles) prior to the tumor manipulation. Biochemical progression is defined as prostate-specific antigen value over 0.2 ng/ml or the initiation of therapy after surgery. Biochemical progression-free, cancer-specific and overall survival curves were calculated by the Kaplan-Meier method. RESULTS: During the study period pre-operative PSA, clinical T stage, duration of surgery, amount of estimated blood loss have decreased. Pathological stage showed a significant downward migration and the rate of positive surgical margin has also decreased. At a mean follow-up of 48 months, 21 men were dead including eight who died of prostate cancer. Overall and cancer-specific survival rates were 97/99% at 5 years and 89/95% at 10 years, respectively. Neoadjuvant hormonal treatment had no beneficial impact on oncological outcome of patients regardless of clinical stage. In 370 patients treated surgically alone, cancer-specific and biochemical progression-free survival rates were 99.6/80.5% at 5 years and 97.9/73.3% at 10 years for patients with clinical T1/2 disease and 95.5/41.9% at 5 years and 87.5/41.9% at 10 years for those with T3 disease, respectively. In the 370 patients biochemical progression-free survival has been significantly improved over the 12-year period (P < 0.0001). CONCLUSIONS: Antegrade radical prostatectomy with preliminary ligation of vascular pedicles can be performed with excellent oncological outcome.

Possibility of recovery of estrogen sensitivity following high-dose glucocorticoid therapy in a patient with hormone-refractory prostate cancer.

A 74-year-old man underwent irradiation therapy (RT) to the prostate bed because of prostate-specific antigen (PSA) failure after retropubic radical prostatectomy (RRP). Six months after the RT, a solitary bone metastasis developed in the third thoracic vertebra, and hormonal therapy (HT) was initiated. Three years later, following the loss of response to all hormonal agents, including oral estrogen and glucocorticoid therapy, paraplegia developed, due to a spinal metastasis. RT and high-dose glucocorticoid therapy were given for the spinal metastasis. Diethylstilbestrol diphosphate (DES-DP) was given continuously during this treatment, except for a 1-month period when the patient had pneumonia. After the RT and high-dose glucocorticoid therapy, his serum PSA decreased, from 308 to 36.99 ng/ml. In accordance with the 1-month discontinuation, and then resumption of DES-DP, the serum PSA levels went up and down. So we suspected that the tumor had recovered sensitivity to DES-DP with the high-dose glucocorticoid therapy. With a further decrease of serum PSA to 2.12 ng/ml, he has been alive for more than 3 years to date since the diagnosis of hormone-refractory prostate cancer (HRPCA). To our knowledge, there have been no reports showing such a marked recovery of hormone-sensitivity in HRPCA. No optimal therapy has yet been established for HRPCA; therefore, high-dose glucocorticoid therapy in combination with DES-DP warrants further study.

Phase I/II study of a combined gemcitabine, etoposide, and cisplatin chemotherapy regimen for metastatic urothelial carcinoma.

BACKGROUND: The authors attempted to determine the maximum tolerated dose (MTD) of gemcitabine in combination with etoposide and cisplatin as a chemotherapy regimen and investigated the safety and antitumor activity with the recommended doses of gemcitabine with etoposide and cisplatin for patients with metastatic urothelial carcinoma. METHODS: Patients age 75 years or younger with measurable lesions, creatinine clearance>or=50 mL per minute, and adequate bone marrow and hepatic function were studied. Etoposide and cisplatin were given on Days 1 through 3 at fixed doses of 75 mg/m2 and 25 mg/m2, respectively, and gemcitabine was given on Days 1, 8, and 15. In the Phase I component, gemcitabine was administered at increasing doses from 600 mg/m2. Cycles were repeated every 28 days unless progressive disease was encountered. RESULTS: In Phase I, with the initially fixed doses of etoposide and cisplatin, the MTD of gemcitabine could not be determined because of the occurrence of dose-limiting toxicity at Level 1 in all 3 patients. When the doses of etoposide and cisplatin were modified to 60 mg/m2 and 20 mg/m2, respectively, the MTD of gemcitabine was 1000 mg/m2. Next, 19 additional patients were entered into Phase II with the recommended gemcitabine dose of 800 mg/m2, and 20 patients in all were treated at this dose level. The main toxicity was bone marrow suppression, with Grade 3 or 4 neutropenia and thrombocytopenia recognized in 20 patients (100%) and 14 patients (70%), respectively, although no toxic deaths occurred. In total, all 31 patients at all dose levels had an assessable response, with 6 complete responses and 15 partial responses observed, for an overall response rate of 67.7%. Patients who had visceral metastasis had a significantly worse response rate than patients who had lymph node metastasis alone (50.0% vs. 78.9%; P=.042). The response rate (66.7%) for 21 patients who received prior chemotherapy was not different from that for 10 chemotherapy-naive patients. The median survival for all patients was 13.1 months, and 4 patients survived for >2 years with no evidence of disease. Patients younger than age 65 years had significantly better survival than patients age 65 years or older (P=.026). CONCLUSIONS: Although bone marrow toxicity was considerable, combination chemotherapy with gemcitabine, etoposide, and cisplatin appeared to be very active in patients with urothelial carcinoma and may be especially promising for younger patients, although further study is warranted.

[Isolated crossed superior rectus palsy in a midbrain infarction].

A 61-year-old man suddenly heard tinnitus and diplopia at night during watchinng television. A few days later he visited at our hospital. Neurologically he exibited marked isolated right superior rectus palsy which was also indicated by the Hess test. No other neurological abnormalities were found such as other ocular muscle paresis, cranial nerve palsies, hemiparesis, sensory impairement or cerebellar ataxia. MRI showed a left medial thalamic infarction extending to a rostral part of the midbrain anterolateral to the cerebral aqueduct at the superior colliculi level. Unilateral superior rectus palsy can rarely be caused by a contralateral midbrain infarction, because fibers from the subnucleus subserving the superior rectus decussate within the oculomoter nerve complex. In this case the crossing fibers toward the contralateral superior rectus may have been selectively involved by a tinny lesion in the area of the oculomotor nucleus. The patient had a slightly narrowed right palpebral fissure. It is indicated that crossing fibers toward the contralateral levator muscle of the eyelid may be also involved. The patient's diplopia completely resolved two months later after the onset.

Successful treatment of chemo-refractory pulmonary metastases of renal pelvic cancer by second-line chemotherapy including gemcitabine followed by salvage surgery.

A 51-year-old woman developed multiple pulmonary metastases after receiving nephroureterectomy and two cycles of adjuvant chemotherapy for the treatment of renal pelvic transitional cell carcinoma. All metastases disappeared after four cycles of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by radiotherapy; however, 8 months later two pulmonary metastases recurred. The patient was entered into a phase I study of combination chemotherapy with gemcitabine, etoposide and cisplatin, designed for chemorefractory urothelial cancer. The lung masses showed significant reduction after two cycles of this chemotherapy; following salvage surgery, the patient has been well with no evidence of recurrence for more than 3 years.

[A young woman with pseudomigraine with CSF pleocytosis].

Migraine is usually not associated with CSF pleocytosis. However, patients with migraine-like severe headache who showed temporary neurological deficits and pleocytosis have recently been accumulated in the literature. Here we report a 20-year-old woman who was admitted to our hospital because of aphasia and right hemiparesis with severe throbbing headache in the left on 15 February, 2001. During the preceding 3 days she experienced another two similar episodes. Lumbar puncure revealed lymphocyte dominant pleocytosis of 56 cells/microliter. These symptoms recovered completely within several hours. EEG showed intermittent theta waves of 4-5c/s, 50-80 microV in the bilateral fronto-parietal region, but no epileptiform activity. On the 12th day 123I-IMP SECT demonstrated rather hyperperfusion in the left fronto-temporo-parietal region. Again, in the early morning on 10 December she was carried to our hospital by an ambulance car because of severe headache, right hemiparesis, expressive and receptive aphasia and drowsiness. Body temperature was 37.9 degrees C and lumbar puncture revealed increased opening pressure of 230 mmH2O and cells of 17/microliter. All the symptoms cleared within 24 hours and she left hospital without any sequelae. The symptoms of this case are consistent with those of headache with neurologic deficits and CSF lymphocytosis (HaNDL) by Berg et al, or pseudomigraine with pleocytosis (PMP syndrome) by Gometz-Aranda et al. No reports have been published on this disease in Japan.

[Successful salvage chemotherapy with gemcitabine, etoposide and cisplatin for metastatic ureteral cancer: a case report].

A 35-year-old man who had undergone nephroureterectomy and a single cycle of adjuvant MVAC chemotherapy for the left ureteral cancer was referred our clinic for the treatment of paraaortic lymph node metastases. Following histologic confirmation of transitional cell carcinoma by computed tomography (CT) guided biopsy, we treated him with combination chemotherapy consisting of ifosfamide, 5-fluorouracil, etoposide and cisplatin. After 5 cycles of chemotherapy complete remission was obtained. Six months later, however, metastases recurred in the left supraclavicular and paraaortic lymph nodes. Thus, we treated him with a new combination chemotherapy comprising gemcitabine, etoposide and cisplatin which was approved as a phase I study by the institutional review board. Although he was the first patient enrolled in the study and received the minimum dose of gemcitabine (level 1), complete remission was again achieved. Adjuvant radiotherapy of 40 Gy was given to the metastatic sites. He has been well without evidence of disease for 12 months.