Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and literature review

Neurological complications during the treatment of hematological malignancies have a wide range of causes. Treatment-related leukoencephalopathy has been recognized as a major complication of combined chemotherapy and radiotherapy for central nervous system (CNS) lymphoma, and can complicate the diagnosis of CNS infection. Herein, we present a patient with diffuse large B-cell lymphoma who developed herpes simplex encephalitis (HSE) and subsequent cytomegalovirus encephalitis after chemoradiotherapy for CNS relapse. Although cerebrospinal fluid examination (CSF) showed no significant pleocytosis, brain magnetic resonance imaging and polymerase chain reaction analysis of the CSF were useful in the diagnosis. With a review of the literature on the association between HSE and radiotherapy for CNS malignancies, our case suggests that an awareness of viral encephalitis is important in the differential diagnosis of acute neurologic disturbance during chemoradiotherapy for CNS lymphoma.     

Enzyme histochemistry is useful to assess viability of tumor tissue after microwave coagulation therapy (MCT): metastatic adenocarcinoma treated by lateral segmentectomy after MCT

We report on a case of metastatic adenocarcinoma of liver that was removed and examined histochemically after microwave coagulation therapy (MCT). The patient was a 65-year-old woman who had a metastatic tumor in the liver (S3) after high anterior resection due to a rectal adenocarcinoma and received MCT against the tumor. One month after MCT, multiple metastatic tumors were detected by abdominal computed tomography (CT) scan. As it was difficult to control them by MCT alone, we performed lateral segmentectomy. To assess the effects of microwave ablation on cellular viability of metastatic tumor, we used enzyme histochemistry for acid phosphatase (AcP), which is positive in macrophages infiltrating in the tumor. In a part of the ablated area of resected liver, there was remaining neoplastic tissue of which the morphology was maintained in H&E staining. This was found to be microwave-fixed non-viable tissue because no enzyme activity of AcP was detected in the infiltrating macrophages. This case report suggests that enzyme histochemistry was useful to assess the effect of MCT, enabling us to distinguish fixed cells from viable cells.     

Influenza A H1N1 pdm09‐associated myocarditis during zanamivir therapy

A 9‐year‐old girl developed influenza A H1N1 pdm09‐associated myocarditis and pericarditis 2 days after starting zanamivir therapy. The virus was detected in the respiratory tract but not in the serum or pericardial effusion. The virus sampled from the respiratory tract had normal susceptibility to neuraminidase inhibitors. Although no differences in interferon‐γ, interleukin (IL)‐1β, and tumor necrosis factor‐α were observed between the plasma and pericardial effusion, some inflammatory cytokines or chemokines (IL‐6 and IL‐8) and vascular endothelial growth factor were remarkably elevated in the pericardial effusion compared with the plasma. This suggested that the influenza virus, after infecting the respiratory tract, affected the myocardium, causing myocarditis to gradually develop, which might have been followed by an autoreactive pericarditis causing increased pericardial effusion. Therefore, influenza‐associated myocarditis should be considered when influenza patients have respiratory and cardiac involvement, even during treatment with a neuraminidase inhibitor.     

The efficacy of oral vitamin A supplementation for measles and respiratory syncytial virus (RSV) infection

Recently, the efficacy of oral vitamin A supplementation for measles and respiratory syncytial (RSV) infection has been evaluated in developing countries. However, in developed countries where vitamin A deficiency is little worth consideration, few studies have been conducted on the effect of vitamin A supplementation. The effect of oral vitamin A (100,000 IU) supplementation was evaluated in 105 children with measles (age 5 months to 4 years) and in 96 children with RSV infection (ages a month to 2.5 years) in Fukushima, Japan. Comparisons were made of clinical signs, duration of hospitalization and complications between treated groups and non-treated groups. Treated group (measles n = 47, RSV n = 54) and non-treated groups (measles n = 58, RSV n = 42) had similar baseline characteristics. Patients with measles given a vitamin A supplementation had a shorter duration of cough (7.2 +/- 1.6 vs 9.2 +/- 1.8 days, p < 0.05) and patients with severe RSV infection given a vitamin A supplementation had a shorter duration of retraction (3.6 +/- 1.4 vs 5.3 +/- 0.8 days, p < 0.05) and wheezing (4.4 +/- 1.7 vs 6.3 +/- 1.5 days, p < 0.05). Toxicities, including excess vomiting and bulging fontanel were not observed. Our findings may suggest the efficacy of oral vitamin A supplementation for measles and severe RSV infection, in children who have no malnutrition.     

Malignant Transformation of the Mouse Anorectal Epithelium Induced by an Inoculated Human Cancer Cell Line

Four kinds of human cancer cell lines and one mouse cancer cell line were inoculated into the subepithelial area of the anorectum of female nude mice. Among the cell lines, two cell lines (KATO III and Lu 135) showed the potential enforcement of atypical changes in the adjacent mouse anorectal epithelium. Moreover, the submucosal invasion of the malignant transformed cells of the mouse epithelium was demonstrated in specimens obtained from three KATO III-inoculated mice. This exciting and novel phenomenon clearly demonstrates the need to change the present general concept of a single-cell origin of cancer tissue. This valuable and novel discovery may change the basis of oncology research while also providing new ideas for projects to investigate the mechanisms of carcinogenesis from several aspects such as molecular biology, cell biology, and pathology. Moreover, the novel experimental design itself is also extremely useful as a simple model for investigating the mechanisms of oncogenesis.     

Comparison of the effects of predilution and postdilution hemodiafiltration on neutrophils, lymphocytes and platelets

Numerous studies have been carried out to investigate the solute removal efficiency of hemodiafiltration (HDF). However, the effect of the dilution mode on blood cell damage during HDF has not yet been examined in detail. Here, we compared predilution and postdilution HDF with respect to their effects on blood cells. Five patients were allocated to one session each of predilution HDF and postdilution HDF. Concentrations of interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, and platelet-derived microparticles (PDMP), and the phagocytotic and sterilizing functions of neutrophils before and after the HDF sessions were evaluated. Lymphocyte blastoid transformation induced by mitogens was also evaluated by measurement of the [³H]-thymidine uptake. The IL-6 and ICAM-1 concentrations decreased after predilution HDF, and increased after postdilution HDF. Lymphocyte blastoid transformation was more pronounced after predilution HDF than after postdilution HDF. There was no significant difference in PDMP between the dilution modes. We conclude that predilution HDF could be more favorable for dialysis patients than postdilution HDF from the point of view of the effects on the blood cells, especially neutrophils and lymphocytes.     

Serum Total Cholesterol Levels Would Predict Nosocomial Infections After Gastrointestinal Surgery

It has been suggested that total cholesterol levels and the use of statin medications are associated with the incidence of complications after gastrointestinal surgery. The aim of this study was to determine if preoperative total cholesterol levels are associated with a higher risk of postoperative infections and mortality. A total of 2211 patients undergoing general surgical procedures between December 2006 and November 2008 at Iizuka Hospital and between January 2010 and March 2012 at Jichi Medical University Hospital were reviewed. Multiple logistic regression models were used to evaluate serum total cholesterol and other variables as predictors of postoperative nosocomial infections. Serum total cholesterol concentrations lower than 160 mg/dl were associated with an increased incidence of superficial and deep incisional surgical site infections. Serum total cholesterol levels showed a reverse J-shaped relationship with the development of organ space surgical site infection and pneumonia. There was no discernible effect of serum cholesterol levels on the postoperative mortality observed in this cohort of patients. Decreased serum albumin was one of the strongest risk factors for the development of nosocomial infection after surgery. Postoperative pneumonia was not observed in patients taking statin medications whose cholesterol levels were <200 mg/dl. Serum total cholesterol may be a valid predictor of surgical outcome. Preoperative statin use may affect the development of postoperative pneumonia in patients with total cholesterol levels below 200 mg/dl.     

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.A long-term goal in contemporary cancer nanomedicine has been to design and generate drug delivery systems that improve the narrow therapeutic window associated with conventional chemotherapeutics (1, 2). Conceptually, several nanotechnology-based entity candidates, including protocells (3), biosynthetic nanoparticles (NPs), viruses, and liposome-based nanoparticles, could be targeted for active delivery through a defined cell surface ligand receptor system and/or physically triggered for finely tuned cargo release (2, 4, 5).Numerous efforts have been made to functionalize NPs by combining them with antibodies, aptamers, peptides, vitamins, or carbohydrates (6–8), but the majority of studies involve untargeted nanoplatforms (4, 9). In practice, targeting NPs is far from trivial, and ongoing challenges include synthesis and purification, selection of an appropriate ligand receptor, and specific composition for NP conjugation. Even the conjugation reaction itself may alter the binding of the tumor-targeting moiety to its receptor through conformational changes, steric freedom restriction, or orientation distortion (10, 11). Unfortunately, the cost-to-benefit ratio of these modifications often elevate the complexity of the NP synthesis, complicating regulatory hurdles because of formulations that are heterogeneous or difficult to reproduce (10, 12, 13).To minimize such drawbacks, NPs can be functionalized via virus-based nanoplatforms as an alternative for targeted cargo delivery (14–16). In particular, filamentous bacteriophage (phage)—a prokaryotic virus—is an attractive candidate to develop a bionanomedicine for cancer therapeutics because phage particles are cost-effectively produced with biological uniformity, as well as being physically robust and stable under harsh conditions (17). Notably, phage-based nanoplatforms are biocompatible and nonpathogenic with eukaryotic organisms and are able to preserve the desired cell targeting and internalization (18). Moreover, phage particles are ideal for incorporating other NPs, which can be released after reaching the tumor site. An admixture of colloidal gold NP (AuNP) with phage particles spontaneously organizes into hydrogel network-like fractal structures (19, 20). These hydrogel networks offer convenient multifunctional integration within a single entity for tumor targeting, enhanced fluorescence and dark-field microscopy, near-infrared (NIR) photon-to-heat conversion, and surface-enhanced Raman scattering (SERS)-based detection (20, 21).In the present work, we developed a tumor targeting theranostic (meaning a combination of therapeutics and diagnostics) hydrogel-based nanoplatform that enables ligand-directed tumor targeting, multimodal imaging capability, and triggered therapeutic cargo release. Our data suggest that targeted hydrogel photothermal therapy represents a functional theranostic approach (fostering “see and treat, treat and see”) in the diagnosis and management of tumors.