Length of mechanical restraint following haloperidol injections versus oral atypical antipsychotics for the initial treatment of acute schizophrenia: A propensity-matched analysis from the Japanese diagnosis procedure combination database

Differences in effectiveness between haloperidol injection and oral atypical antipsychotics in the acute-phase treatment of schizophrenia are not well examined. We retrospectively investigated whether these treatment options affected the length of mechanical restraint. We used the Japanese Diagnosis Procedure Combination Database to identify schizophrenia patients who were involuntarily hospitalized and receiving mechanical restraint between July and December, 2006–2009. Data included patient demographics, use of antipsychotics, and number of days on which patients underwent mechanical restraint. Propensity score matching was performed to compare the number of days of mechanical restraint between the haloperidol injection group and the oral atypical antipsychotics group. We used survival analysis to examine whether the initial difference in treatment affected the number of days of mechanical restraint. Cox regression was performed to compare the concurrent effects of various factors. Among 1731 eligible patients, 574 were treated with haloperidol injections and 420 with atypical antipsychotics. Matching produced 274 patients in each group. Cox regression analysis showed that the initial therapeutic agents did not significantly affect the number of days of mechanical restraint. The results indicate that atypical antipsychotics were as effective as haloperidol injections in the acute-phase treatment of schizophrenia.     

Immune-related adverse events and prognosis in patients with upper gastrointestinal cancer treated with nivolumab

BackgroundImmune checkpoint inhibitors (ICIs) are increasingly being used for the treatment of upper gastrointestinal cancers [esophageal cancer and gastric cancer (GC)]. They cause imbalances in immunological tolerance, resulting in immune-related adverse events (irAEs). Although irAEs have been reported to be associated with the efficacy of ICIs in some cancers, the relationship between irAEs and prognosis of upper gastrointestinal cancers remains unknown. This study aimed to investigate the prognostic impact of irAEs in patients with advanced or recurrent upper gastrointestinal cancer treated with nivolumab.MethodsWe retrospectively divided the patients (n=96) who received nivolumab into two groups: the irAEs group (n=41) and non-irAEs group (n=55), according to the Common Terminology Criteria for Adverse Events ver. 5.0.ResultsirAEs were significantly associated with good performance status and high serum albumin levels (all P<0.05). The irAEs group had a significantly longer overall survival (OS) than the non-irAEs group [log-rank P=0.003; univariate hazard ratio (HR) =0.36, 95% confidence interval (CI) =0.21–0.65, P<0.01; multivariate HR =0.47, 95% CI =0.26–0.88, P=0.018]. Importantly, in both esophageal cancer and GC, the irAEs group experienced favorable clinical outcomes compared with the non-irAEs group. In the multivariate analysis, male sex (P<0.01), presence of irAEs (P=0.018), and good pretreatment performance status (P<0.01) were independent prognostic factors.ConclusionsAmong patients with upper gastrointestinal cancer treated with nivolumab, the prognosis of patients who developed irAEs was better than that of patients who did not develop irAEs. Long-term continuation of nivolumab by early detection of irAEs and an appropriate response to irAEs are important.     

Characteristics and Prognosis of Stroke in Living Donor Renal Transplant Recipients

Aims: We aimed to determine the characteristics and vascular outcomes of stroke in renal transplant (RT) recipients and compare them with those in patients on hemodialysis (HD) and those with no renal replacement therapy (RRT). Methods: In this prospective observational study, 717 patients (mean age, 70.8 years; male, 60.5%) with acute ischemic stroke within one week of onset were consecutively enrolled and followed for one year. The patients were classified into three groups: (1) living donor RT recipients (n=27); (2) patients on maintenance HD before the index stroke (n=39); and (3) those with no history of RRT (n=651). The primary outcome was a composite of major adverse cardiovascular events (MACE). Results: Diabetic nephropathy was the most common reason for RRT in both RT and HD patients. RT patients were more likely to have embolic stroke of undetermined source (33.3%) than others, whereas HD patients more often had cardioembolism (51.3%). No difference was observed in the MACE risk between the patients in RT and non-RRT groups (annual rate, 11.3% vs. 13.1%; log-rankP=0.82; hazard ratio [95% confidence interval], 0.92 [0.29-2.98]). In contrast, HD patients had a greater risk of MACE than those with no RRT (annual rate, 28.2% vs. 13.1%; log-rankP=0.019; hazard ratio [95% confidence interval], 2.24 [1.16-4.3]). Conclusions: The underlying etiologies of stroke differed in RT and HD patients. The one-year risk of MACE for stroke patients who had received an RT was lower than that for patients undergoing HD and comparable with that of patients with no RRT.     

Survival impact of immune cells infiltrating peritumoral area of hepatocellular carcinoma

Inflammatory and immune cells in the tumor microenvironment are reported to be associated with tumor progression in several cancers. In total, 225 patients who underwent initial and curative hepatectomy for hepatocellular carcinoma (HCC) from 2004 to 2013 were enrolled in this study. Tumor‐associated neutrophils (TANs), M2 macrophages (TAMs; tumor‐associated macrophages), CD8⁺ T cells, and regulatory T cells (Tregs) were evaluated by immunohistochemistry (IHC), and their relationships with patient clinicopathological characteristics and prognosis were evaluated. IHC was performed focusing on TANs first. We could not find a relationship between intratumoral and peritumoral TANs and clinicopathological features except for the fibrous capsule and infiltration of tumors into capsule. Next, TAMs, CD8⁺ cells and Tregs were evaluated by IHC. At the peritumoral area, TANs and TAMs (r = 0.36, p = 0.001) or Tregs (r = 0.16, p = 0.008) showed a positive correlation, whereas TANs and CD8⁺ cells showed a negative correlation (r = −0.16, p = 0.02). As for survival outcomes, at the peritumoral area, high TANs (p = 0.0398), low CD8⁺ cells (p = 0.0275), and high TAMs (p = 0.001) were significantly associated with worse overall survival (OS). In addition, high TANs (p = 0.010), and high TAMs (p = 0.00125) were significantly associated with worse disease‐free survival (DFS). Finally, we established a risk signature model by combining the expression patterns of these cells. The high‐risk signature group had significantly worse OS (p = 0.0277) and DFS (p = 0.0219) compared with those in the low‐risk signature group. Our risk signature based on immune cells at the peritumoral area of the HCC can predict patient prognosis of HCC after curative hepatectomy.     

Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening

Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer-promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein-coupled receptor for short-chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT-PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short-chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract. ( Cancer Sci 2009)     

Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients

Abstract. Nishimura N, Hachisuga T, Saito T, Kawarabayashi T. Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients.
This study aimed to detail the clinicopathologic features of endometrial carcinomas that developed in Japanese patients receiving adjuvant tamoxifen treatment for breast cancer patients. Ten endometrial carcinomas in tamoxifen-treated breast cancer patients were collected from two medical centers. The endometrial carcinomas included two stage Ia, four stage Ib, two stage Ic and two stage IIIc. Three tumors were Grade 1, six were Grade 2, and one was Grade 3. The tumor was limited to the endometrium in two cases. Myometrial invasion was limited to the inner half of the myometrium in five cases and involved the outer half in three. A mild degree of lymphovascular space invasion was identified in five cases. Deep cervical invasion was recognized in one case. The cell types comprised nine endometrioid adenocarcinomas and one serous carcinoma. Five of eight postmenopausal endometrial carcinomas were associated with polypoid endometrial lesions composed of cystically dilated atrophic and proliferative glands widely separated by fibrotic stroma. Two patients with retroperitoneal lymph node metastases died of endometrial cancer. One patient developed a contralateral breast cancer during tamoxifen treatment. No patient died of breast cancer. We did not demonstrate a higher frequency of either high-grade tumors or unfavorable histologic subtypes in tamoxifen-treated Japanese breast cancer patients.