Randomized open-label study of second-generation antipsychotics for the treatment of schizophrenia: 104-week final results of the JUMPs study assessing treatment discontinuation, remission, and social functioning.

BACKGROUND: We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study. METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension). RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation. CONCLUSIONS: The 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment. CLINICAL TRIAL REGISTRATION: UMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012).

Discontinuation and remission rates and social functioning in patients with schizophrenia receiving second-generation antipsychotics: 52-week evaluation of JUMPs, a randomized, open-label study.

AIM: Globally, evidence from short-term studies is insufficient for the guidelines to uniformly recommend a particular antipsychotic(s) for the maintenance treatment of schizophrenia. Therefore, long-term comprehensive evaluation of antipsychotics is required from a social rehabilitation perspective, especially for drugs that have not yet been studied. The Japan Useful Medication Program for Schizophrenia (JUMPs) is a large-scale, long-term naturalistic study to present pivotal 52-week data on the continuity of second-generation antipsychotics (SGA: aripiprazole, blonanserin, and paliperidone). METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 52-week study. Enrolled patients had schizophrenia, were ≥20 years old, and required antipsychotic treatment or switched from previous therapy. The primary endpoint was treatment discontinuation rate over 52 weeks. Secondary outcomes included remission rate, social functioning, and quality-of-life scores [Personal and Social Performance Scale (PSP) and EuroQol-5 dimensions], and safety. RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). The discontinuation rate (P = 0.9771) and remission rates (P > 0.05) over 52 weeks did not differ significantly between the three treatment groups. The discontinuation rates were 68.3%, 68.2%, and 65.5% in the aripiprazole, blonanserin, and paliperidone groups, respectively. Significant improvements (all P < 0.05) from baseline in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favored blonanserin. CONCLUSION: All three SGAs evaluated in this study showed similar treatment discontinuation rates in patients with chronic schizophrenia in Japan.

[A CASE OF RAPIDLY ADVANCING RENAL MUCINOUS TUBULAR AND SPINDLE CELL CARCINOMA].

Renal mucinous tubular and spindle cell carcinoma (MTSCC) is a rare, renal epithelial neoplasm that is an established subtype in the World Health Organization 2004 classification. A 75-year-old-woman was diagnosed as having atypical mycobacterial infection and hepatitis C. Computed tomography showed a hypovascular mass 35 mm in diameter in the left kidney. The renal tumor was diagnosed as MTSCC by pathological examination of the renal biopsy specimen. The patient underwent laparoscopic left radical nephrectomy via a retroperitoneal approach. Pathological findings showed left renal carcinoma (MTSCC, pT3aN0M0), and we did not perform adjuvant therapy. The patient developed lung nodules one month after the operation that were diagnosed as lung metastasis by pathological examination of a bronchoscopic biopsy specimen. She then developed progression of lung metastasis, mediastinal lymph node metastasis and bone metastasis. We explained the necessity of therapy, but she refused therapy and died of disease progression four months after the operation. MTSCC is thought to have a relatively good prognosis, but care must be taken because, as in our case, tumor progression can occur rapidly.

Tubular nephrotoxicity induced by docetaxel in non-small-cell lung cancer patients.

Renal dysfunction is a characteristic of many patients with cancer; however, a standard therapy has not been established for stage III or IV non-small-cell lung cancer (NSCLC) complicated with chronic renal failure. Docetaxel has a proven significant activity against NSCLC. This agent is predominantly eliminated by hepatobiliary extraction and is safe in patients with renal failure, including dialysis patients. Docetaxel is, thus, a therapeutic option in that patient population. Here, we report acute tubular nephrotoxicity secondary to docetaxel in NSCLC patients, even in patients with normal renal function. Little is known about tubular nephrotoxicity induced by docetaxel; however, oncologists should be aware of its possibility.

[A case of locally advanced non-small-cell lung cancer complicated with chronic renal failure and gastric cancer, successfully treated with weekly docetaxel and concurrent thoracic radiotherapy].

A standard therapy is not established for locally advanced non-small-cell lung cancer(NSCLC)complicated with chronic renal failure, although some cases of the disease have been reported. We report a case of a locally advanced squamous cell carcinoma of the lung, complicated with chronic renal failure. He was successfully treated with weekly docetaxel(DOC)and concurrent thoracic radiotherapy, and no deterioration of renal function was observed. In locally advanced NSCLC complicated with renal dysfunction, treatment with weekly DOC and concurrent thoracic radiotherapy is considered to be a therapeutic option. Since radiation pneumonitis occurred in the present case, the accumulation and precise analysis of applicable cases is an important subject for future consideration.

[A case of malignant lymphoma successfully diagnosed using Sasada transbronchial angled biopsy forceps].

A 68-year-old man was referred to our hospital due to general fatigue, fever and weight loss. His chest radiograph showed a nodule (2.8 cm) in the right middle lobe. Computed tomography and positron emission tomography showed multiple metastases to the bone, liver and lymph nodes. The lung nodule was not accessible by standard transbronchial forceps. However, biopsy specimens obtained using Sasada Transbronchial Angled Biopsy Forceps (STAF) pathologically confirmed the diagnosis of malignant lymphoma. We report the case, and discuss the utility of STAF for lung lesions that are difficult to access with standard forceps.

[An autopsy case of sarcomatoid malignant mesothelioma mimicking adenocarcinoma with sarcomatoid elements of lung].

A 62-year-old man with pain in his hip joints and back was admitted to our hospital. His chest radiograph and CT showed a huge mass extending from the left upper pericardium to the left hilum, but no pleural effusion or other lesions. A contrast-enhanced abdominal CT showed multiple metastases to bones and both kidneys. Bronchoscopy revealed obstruction of the left B3 by a visible tumor. The biopsy specimens of the initial immunohistochemical staining were slightly positive for calretinin. However, we diagnosed the condition as sarcomatoid carcinoma of the lung on the basis of the clinical evaluation. Although radiotherapy was administered, his condition rapidly deteriorated and he died due to progression of the disease. Autopsy revealed extensive invasion, suggesting mesothelioma. Therefore, immunohistochemical staining was performed; the findings revealed sarcomatoid malignant mesothelioma. In conclusion, we encountered a rare case of sarcomatoid malignant mesothelioma (stage IV).

[A case of severe COPD associated with tracheo-bronchial stenosis, treated with non-invasive positive pressure ventilation].

A 76-year-old man was admitted with acute exacerbation of COPD. He was administered bronchodilators, antibiotics and oral corticosteroids. Although his cough, sputum, fever and the laboratory data improved. wheezing and dyspnea remained. The chest CT revealed severe stenosis of the trachea and both main bronchi, which was thought to be the cause of the symptoms, and similar to the condition of "excessive dynamic airway collapse (EDAC)". We treated him with NPPV and his symptoms improved and he returned home. "EDAC"-like tracheobronchial stenosis with COPD treated with NPPV is rare.

[A case of prostatic adenocarcinoma clinically presenting as supraclavicular and mediastinal lymphadenopathy].

We report a 70-year-old man with prostatic carcinoma presenting as supraclaviculer and mediastinal lymphadenopathy. He had no urinary tract symptoms, and computed tomography and FDG-PET showed no abnormality in the prostate or pelvic lymph nodes. Metastatic prostatic adenocarcinoma was finally diagnosed from the results of immunohistochemical staining for PSA of a biopsy specimen of the mediastinal lymph node, and he was treated by hormonal therapy. There are fears that some other similar cases might be treated with chemotherapy as lung cancer without immunohistochemical staining. Prostatic carcinoma should always be considered in the differential diagnosis of elderly men with supraclaviculer or mediastinal lymph node metastases, since appropriate treatment will lead to a prolonged survival.

Minocycline-induced vasculitis fulfilling the criteria of polyarteritis nodosa.

A 47-year-old man who had been taking minocycline for palmoplantar pustulosis developed fever, myalgias, polyneuropathy, and testicular pain, with elevated C-reactive protein (CRP). Neither myeloperoxidase- nor proteinase-3-antineutrophil cytoplasmic antibody was positive. These manifestations met the American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Stopping minocycline led to amelioration of symptoms and normalization of CRP level. To our knowledge, this is the second case of minocycline-induced vasculitis satisfying the criteria. Differential diagnosis for drug-induced disease is invaluable even for patients with classical polyarteritis nodosa.

[Case of primary Sjögren's syndrome with hypereosinophilia and elevation of serum IgE: measurements of serum IL-4, IL-5 and the IgG subclass].

A 62-year-old man admitted to our hospital because of dry eyes and thirst. On admission, his bilateral parotid and submandibular glands were swelling. Laboratory data revealed severe eosinophilia (3309/microl), elevated serum IgE (1821IU/dl) and hypergammaglobulinemia (IgG 6049 mg/dl). Interstitial pneumonia and renal dysfunction were present. He was diagnosed with Sjögren's syndrome (SjS) according to the European criteria. After the initiation of the therapy with 30 mg of prednisolone, all abnormal findings including salivation ameliorated promptly. In the absence of any other obvious causes of eosinophilia and elevation of serum IgE, these findings might be associated with SjS itself. Moreover, both serum IL-5 and IgG4 levels were elevated in this patient, suggesting that Th2 type cytokines were dominant. Elevation of serum IgE and IgG4, and hypereosinophilia were likely to be reactive. To our knowledge, there have been no reports of these cytokines and of IgG subclass in such patients. We propose the existence of Th2-type-cytokine-dominant subtype of SjS.