A phase II study of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed or refractory non-Hodgkin lymphoma.

This study evaluated the efficacy and safety of salvage chemotherapy with gemcitabine, carboplatin, dexamethasone, and rituximab (GCD ± R) for Japanese patients with relapsed or refractory non-Hodgkin lymphoma (NHL). A multicenter, phase II trial of GCD ± R administered every 3 weeks for up to 6 cycles was conducted. Rituximab was administered as a therapeutic strategy for CD20-positive lymphoma. The primary endpoint was the complete response (CR) rate. Secondary endpoints included the overall response (OR) rate, overall survival (OS), progression-free survival (PFS), toxicity, and success rate of peripheral blood stem cell collection for eligible transplant patients. A total of 25 patients (median age 66 years) were evaluated, with a median follow-up period of 66.7 months. CR and OR rates were 28% and 52%, respectively. Median PFS and OS were 8.7 and 32.2 months, respectively. The major toxicity was myelosuppression, but the regimen was generally well-tolerated, with a low incidence of febrile neutropenia (20%) and no treatment-related deaths. Of the 6 patients who were eligible for autologous stem cell transplantation and underwent peripheral blood stem cell mobilization, the required number of CD34-positive cells was collected in 5 (83%). All 6 proceeded to transplantation and achieved successful engraftment without recurrence. The present results suggest that GCD ± R may be effective and well-tolerated in Japanese patients with relapsed or refractory NHL. However, further investigation is needed to confirm these results.

Not Oligomers but Amyloids are Cytotoxic in the Membrane-Mediated Amyloidogenesis of Amyloid-ß Peptides.

The formation of neurotoxic aggregates by amyloid-ß peptide (Aß) is considered to be a key step in the onset of Alzheimer's disease. It is widely accepted that oligomers are more neurotoxic than amyloid fibrils in the aqueous-phase aggregation of Aß. Membrane-mediated amyloidogenesis is also relevant to the pathology, although the relationship between the aggregate size and cytotoxicity has remained elusive. Here, aggregation processes of Aß on living cells and cytotoxic events were monitored by fluorescence techniques. Aß formed amyloids after forming oligomers composed of ≈10 Aß molecules. The formation of amyloids was necessary to activate apoptotic caspase-3 and reduce the ability of the cell to proliferate; this indicated that amyloid formation is a key event in Aß-induced cytotoxicity.

Impact of Skeletal Muscle Depletion on Patients with Myelodysplastic Syndrome Treated with Azacitidine.

BACKGROUND: Azacitidine (AZA) is the standard treatment for patients with high-risk myelodysplastic syndromes (MDS). The impact of skeletal muscle depletion (SMD), which is associated with outcomes of hematological malignancies, on the clinical course of MDS patients treated with AZA was investigated. METHODS: This retrospective, observational study included 50 MDS patients treated with AZA. Muscle mass was evaluated using the skeletal muscle index (SMI), which is the area of muscle mass at the third lumbar vertebra on CT images divided by the square of the height. RESULTS: Of the enrolled patients, 39 were males, and their median age was 69.5 years. Twenty-seven (20 male and 7 female) patients showed SMD. The median survival was 13.4 months in the SMD group and 15.2 months in the non-SMD group, with no significant difference and no significant association between the response rate or severe non-hematological toxicities and the presence of SMD. By contrast, grade 3-4 anemia and thrombocytopenia were significantly more frequent in the SMD group than in the non-SMD group. SMD was associated with severe anemia and thrombocytopenia in MDS patients treated with AZA. CONCLUSION: Reduced skeletal muscle mass may predict severe hematological toxicity in MDS patients treated with AZA.

The pretreatment Controlling Nutritional Status score is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma.

Predicting prognosis is crucial in older patients with diffuse large B-cell lymphoma (DLBCL). This study evaluated the prognostic impact of the controlling nutritional status (CONUT) score, a simple nutritional index, for older DLBCL patients (≥65 years of age) treated with R-CHOP-like regimens in a retrospective, cohort study including 203 patients. The CONUT score was an independent prognostic factor for overall survival (hazard ratio 1.11, 95% confidence interval (CI) 1.01-1.21, p = 0.032) in a multivariable Cox proportional hazards model. On receiver-operating characteristic analysis, the optimal cutoff value was 3. The CONUT score (≥3 or <3) effectively stratified older DLBCL patients, regardless of the International Prognostic Index (p = 0.71 for interaction). Further, the CONUT score independently affected initial dose intensity (odds ratio 0.84, 95% CI 0.73-0.95, p = 0.008), likely reflecting the patients' status at diagnosis and affecting dose adjustments. In conclusion, the CONUT score is associated with a poorer prognosis in older DLBCL patients.

Severe skin ulcer caused by taking lenvatinib after proton beam therapy.

A 69-year-old man was treated with lenvatinib after three sessions of proton beam therapy (PBT) for hepatocellular carcinoma. Five months after administration of lenvatinib, a dermatitis with huge skin ulcer formed in the site of PBT irradiation. Lenvatinib was immediately withdrawn, but the skin ulcer continued growing until about 2 weeks later. With topical and antibiotic treatment, the skin ulcer resolved after about 4 months. After administration of lenvatinib, potential skin damage due to PBT at the irradiated site may have become apparent. This is the first report describing skin ulcer by the combination of lenvatinib administration and PBT.

Improvement of Rectal Prolapse Using an Over-the-scope Clip System.

Rectal prolapse is typically treated surgically, and internal therapy has not been reported. We encountered a case of rectal prolapse that improved with an over-the-scope clip system (OTSC). An 81-year-old woman complaining of anorectal pain underwent colonoscopy, and rectal prolapse was observed prior to colonoscopy. Unfortunately, rectal perforation occurred while attempting endoscopic reversal. The OTSC system was used to close the rectal perforation and subsequently improved her rectal prolapse, probably because the rectal wall was anchored to the retroperitoneum. This is the first report to show that rectal prolapse can be endoscopically improved and that an OTSC system might be a viable alternative method for managing inoperable rectal prolapse.

Comparison of the prognostic impact of IPI and PIT in peripheral T-cell lymphoma in real-world practice with a large elderly population.

We compared the predictive ability of the International Prognostic Index (IPI), a frequently used prognostic model for peripheral T-cell lymphoma (PTCL), with that of a type-specific prognostic model, the Prognostic Index for PTCL-U (PIT). We retrospectively analyzed 113 patients diagnosed with PTCL. The median age was 67 years (range, 16-88 years), 75 patients (66%) were male, and the most common disease type was PTCL, not otherwise specified (69%). With a median follow-up of 6.8 years (interquartile range, 2.7-9.9 years), 5-year survival rates for the four groups in IPI were 85%, 62%, 49%, and 13%, respectively. Similarly, 5-year survival rates for the four groups in PIT were 83%, 64%, 49%, and 19%, respectively. The area under the receiving operating characteristic curve for predicting mortality from PIT (0.725) was not significantly different from that from the IPI (0.685, P = 0.134). Multivariable analysis showed that performance status ≥ 2 (P < 0.0001) and extranodal lesions ≥ 2 (P = 0.029) were significantly associated with lower overall survival. The present study found no significant difference in prognostic ability between the IPI and PIT for PTCL, and both models appear useful as predictive models.

Intramuscular Bleeding Triggered by Disseminated Intravascular Coagulation with Enhanced Fibrinolysis in a Patient with Prostate Cancer.

Disseminated intravascular coagulation (DIC) is the most frequent coagulation disorder associated with solid tumors, including prostate cancer. We herein report a 76-year-old man who suffered from intramuscular bleeding of the right gluteus maximus. Laboratory data showed a pattern of DICwith enhanced fibrinolysis, and a general examination led to the diagnosis of advanced prostate cancer with multiple bone metastases. To our knowledge, this is the first report describing intramuscular bleeding as an initial manifestation of prostate cancer with DIC with enhanced fibrinolysis.

Prognostic impact of the controlling nutritional status score in patients with peripheral T-cell lymphoma.

The controlling nutritional status (CONUT) score is a simplified nutritional index calculated from serum albumin, total cholesterol, and total lymphocyte count. This study evaluated the prognostic impact of the CONUT score on overall survival (OS) in patients with peripheral T-cell lymphoma (PTCL). A multicenter, retrospective cohort study including 99 patients with PTCL was conducted. The CONUT score was significantly higher in the non-survivor group (median 5, range 0-12) than in the survivor group (median 3, range 0-11; p = 0.026). The CONUT score was an independent prognostic factor in a multivariable Cox proportional hazards model (hazard ratio 1.119, 95% confidence interval 1.021-1.227, p = 0.017). No significant effect-modification by the International Prognostic Index (IPI) was observed, and the CONUT score affected the prognosis of PTCL regardless of the IPI (P for interaction = 0.208). In conclusion, the CONUT score is an independent prognostic factor for PTCL irrespective of IPI category.

Risk factors for the development of esophageal candidiasis among patients in community hospital.

The aim of this study was to clarify risk factors for esophageal candidiasis (EC) in immunocompetent patients in a community hospital. 7736 patients who underwent esophagogastroduodenoscopy at our hospital from April 2012 to July 2018 were enrolled. The relationships between EC and the following factors: age, gender, body mass index, lifestyle, lifestyle-related diseases, medication, and endoscopic findings were analyzed. EC was observed in 184 of 7736 cases (2.4% morbidity rate). Multivariate analysis revealed that significant risk factors for the development of EC were: diabetes mellitus {odds ratio (OR): 1.52}, proton pump inhibitor (PPI) use (OR: 1.69), atrophic gastritis (AG) (OR: 1.60), advanced gastric cancer (OR: 4.66), and gastrectomy (OR: 2.32). When severe EC (Kodsi grade ≥ II) was compared to mild EC (grade I), the most significant risk factors were advanced gastric cancer (OR: 17.6) and gastrectomy (OR: 23.4). When considering the risk of AG and PPI use with EC development, the risk increased as follows: AG (OR: 1.59), PPI use (OR: 2.25), and both (OR: 3.13). PPI use, AG, advanced gastric cancer and post-gastrectomy are critical risk factors for the development of EC. We suggest close monitoring for EC development when PPIs are administered to patients with these factors.

Effects of antithrombotic drugs on the results of fecal immunochemical test in colorectal neoplasms screening.

Fecal immunochemical test (FIT) is widely used as a colorectal cancer screening tool. Antithrombotic drugs may affect the screening performance of FIT for colorectal tumors. The aim of this study was to clarify the effect of antithrombotic agents on FIT accuracy in screening for colorectal neoplasms. This retrospective study enrolled a total of 758 patients who underwent both FIT and total colonoscopy. The effect of antithrombotic drugs on FIT accuracy in detecting colorectal neoplasms (CN), including colorectal cancer (CRC), advanced adenoma (AA), and non-advanced adenoma (NAA), was examined. Of the 758 patients, 144 (19%) received antithrombotic drugs (administration group). In administration group, 61/144 (42%) cases had CN [CRC:14, AA:15, NAA:32] and 217/614 (35%) cases had CN (CRC:43, AA:56, NAA:118) in non-administration group. The prevalence of CN was not significantly different between the two groups (p = 0.1157). There was no significant difference in sensitivity or specificity of the detection of all types of CN with or without taking antithrombotic drugs. Neither the positive predictive value nor negative predictive value of FIT was affected by antithrombotic drug administration. Taking antithrombotic drugs may not have a large impact on sensitivity, specificity, positive predictive value, or negative predictive value of FIT in screening for CN.

Molecular Mechanism of Apoptosis by Amyloid ß-Protein Fibrils Formed on Neuronal Cells.

Aggregational states of amyloid ß-protein (Aß) are critical for its neurotoxicity, although they are not well-characterized, particularly after binding to the cell membranes. This is one reason why the mechanisms of Aß neurotoxicity are controversial and elusive. In this study, the effects of toxic Aß-(1-42) fibrils formed in the membrane on cellular processes were investigated using human neuroblastoma SH-SY5Y cells. Consistent with previous observations, fibrillar Aßs formed on the membranes induced activation of caspase-3, the effector caspase for apoptosis. Knockdown analyses of the initiator caspases, caspase-8 and caspase-9, indicated that the apoptosis was induced via activation of caspase-8, followed by activation of caspase-9 and caspase-3. We also found that inflammation signaling pathways including Toll-like receptors and inflammasomes NOD-, LRR-, and pyrin domain-containing protein 3 are involved in the initiation of apoptosis by the Aß fibrils. These inflammation-related molecules are promising targets for the prevention of apoptotic cell death induced by Aß.