Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. Recently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma. Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical expression of SIRT1, p53, bcl2, CD10, bcl6, and multiple myeloma-1 (MUM1) were evaluated by using a 2 mm core from 104 DLBCL patients for tissue microarray. Positive expression of SIRT1 was seen in 74% (77/104) of patients. In total DLBCL patients, SIRT1 and p53 expression were significantly associated with shorter overall survival (OS) by univariate analysis (P=0.001 and P=0.011, respectively). SIRT1 was also an independent prognostic factor by multivariate analysis (P=0.01). According to the expression patterns of CD10, bcl6, and MUM1, germinal center B cell (GCB) types were represented in 38 cases (37%) and non-GCB types were represented in 66 cases (63%). In the GCB type, only p53 expression was associated with a significantly shorter OS (P=0.032). In the non-GCB type, expression of SIRT1 correlated with shorter OS by univariate analyses (P=0.005) and multivariate analyses (P=0.049). In conclusion, we showed that SIRT1 expression is a clinically significant prognostic indicator for DLBCL patients.

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Tumor-infiltrating immune cells perform a crucial function in host immune reactions against diffuse large B-cell lymphoma (DLBCL). In this study, we have identified a subset of tumor-infiltrating FOXP3-positive regulatory T cells (Tregs) in the initial DLBCL biopsy specimens, and have evaluated their prognostic significance. Ninety six patients with DLBCL were evaluated retrospectively. The pattern of FOXP3 protein expression was evaluated using standard immunohistochemistry in paraffin-embedded tissue samples. Sixty seven of all 96 specimens were stained with antibodies for CD-10, bcl-6 and MUM1 via tissue microarray (TMA) to classify the cases into a germinal center B-cell like (GCB) group and a non-GCB group. The median overall survival (OS) was 28 months. As compared with the others, the patients with higher percentages of FOXP3-positive Tregs on initial tumor biopsy evidenced a significantly longer OS (p = 0.003). Patients classified into the GCB group evidenced a significantly longer OS as compared with the non-GCB group (p = 0.008). When the prognostic factors were evaluated via a multivariate model, the international prognostic index and the percentage of infiltrating FOXP3-positive Tregs in the initial biopsy were identified as independent predictors of OS. In conclusion, the presence of an increased percentage of FOXP3-positive Tregs in DLBCL is predictive of better prognoses.

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BackgroundDrug-induced nephrotic syndrome (NS) can be resolved by eliminating the causative agents. However, patients with metastatic cancer have not been previously reported to achieve complete recovery from anticancer drug-induced NS after discontinuation of treatment, because many patients die of cancer progression before NS is restored.Case presentationA 67-year-old man presented with edema of both lower extremities. He received pazopanib therapy for recurrent metastatic renal cell carcinoma (mRCC) for 17 months. Laboratory examinations revealed 7484.58 mg/day of 24-h urine protein, 434 mg/dL of serum cholesterol, and 2.9 g/dL of serum albumin. He was diagnosed with NS, and pazopanib treatment was discontinued. Four months later, he completely recovered from NS. He was then treated with temsirolimus and nivolumab sequentially for > 26 months. Pazopanib was re-introduced following disease progression, and demonstrated antitumor effects for 7 months without NS recurrence.ConclusionPazopanib-induced NS can occur late in patients with mRCC, and its subsequent discontinuation can enable patients to completely recover from its adverse effects. Moreover, pazopanib treatment may be re-introduced without the recurrence of NS.

Objective: In the present study, we characterized the vestibulo-ocular reflex (VOR) gain and properties of corrective saccades (CS) in patients with posterior inferior cerebellar artery (PICA) stroke and determined the best parameter to differentiate PICA stroke from benign peripheral vestibular neuritis (VN). In particular, we studied CS amplitude and asymmetry in video head impulse tests (vHITs) to discriminate these two less-studied disease conditions.Methods: The vHITs were performed within 1 week from symptom onset in patients with PICA stroke (n = 17), patients with VN (n = 17), and healthy subjects (HS, n = 17).Results: PICA stroke patients had bilaterally reduced VOR gains in the horizontal semicircular canal (HC) and the posterior semicircular canal (PC) compared with HSs. When compared with VN patients, PICA stroke patients showed preserved gains in the HC and anterior semicircular canal (AC) bilaterally (i.e., symmetric VOR gain). Similar to VOR gain, smaller but bilaterally symmetric CS in the HC and AC were observed in PICA stroke patients compared with VN patients; the mean amplitude of CS for the ipsilesional HC was reduced (p < 0.001, Mann–Whitney U-test), but the mean amplitude of CS for the contralesional HC was increased (p < 0.03, Mann–Whitney U-test) in PICA stroke compared with VN. The receiver operating characteristic (ROC) curve showed that CS amplitude asymmetry (CSs) and VOR gain asymmetry (Gs) of HC are excellent parameters to distinguish PICA stroke from VN.Conclusion: In the current study, we quantitatively investigated the VOR gain and CS using vHITs for three semicircular canals in PICA stroke and VN patients. In addition to VOR gain, quantitative assessments of CS using vHITs can provide sensitive and objective parameters to distinguish between peripheral and central vestibulopathies.

The prognostic relevance of tumor human papillomavirus (HPV) status in anal squamous cell carcinoma (SCC) had not been previously investigated, although its relevance to cervical, head and neck SCC is known. We retrospectively evaluated outcomes in 47 patients with anal SCC treated with combined chemoradiotherapy (CCRT) and determined tumor HPV status by HPV DNA chip method and p16 expression by immunohistochemistry (IHC) from paraffin-embedded tumor tissues. The median age was 65 years (range, 44-90 years). Sixteen (34%) patients were diagnosed with T stage 3 to 4, and 18 (38%) patients had regional nodal disease (N-positive). Thirty-five (75%) patients were HPV positive, and 31 (66%) patients were genotype 16 (HPV16-positive). Thirty-nine (83.0%) patients were positive for p16. After median follow-up of 51.7 months (range, 5.1-136.0 months), HPV16-positive group had significantly better 4-year progression-free survival (PFS, 63.1% vs. 15.6%, p < 0.001) and overall survival (84.6% vs. 39.8%, p 5 0.008) than HPV genotype 16 negative (HPV16-negative) group. Patients with p16-positive tumor also had a better 4-year PFS (52.5% vs. 25.0%, p 5 0.014) than those with p16-negative tumor. In multivariate analysis for PFS, N-positive and HPV16-negative were independent prognostic factors for shorter PFS. Comparing patterns of failure, time to loco-regional failure was statistically superior in HPV16-positive over HPV16-negative groups (p 5 0.006), but time to systemic failure was not different (p 5 0.098). Tumor HPV genotype 16 status is a prognostic and predictive factor in anal SCC treated with CCRT, and p16 expression determined by IHC might be advocated as a surrogate biomarker of HPV integration in anal SCC. Further studies are warranted.Anal squamous cell carcinoma (SCC) is an uncommon malignancy of the anal canal and perianal skin area. The clinical biology of anal SCC is distinct from other gastrointestinal tract cancers. It is mostly a loco-regional disease at diagnosis, with metastasis in only 15% of patients.1 Therefore, in managing anal cancer, the concerns of treatment strategies include improving loco-regional control and preserving sphincter function. Combined chemoradiotherapy (CCRT)

Objective: Intravenous contrast agent enhanced, high-resolution magnetic resonance imaging of the inner ear (iMRI) confirmed that patients with Menière's disease (MD) and vestibular migraine (VM) could present with endolymphatic hydrops (EH). The present study aimed to investigate EH characteristics and their interrelation to neurotologic testing in patients with VM, MD, or VM with concurrent MD (VM-MD).Methods: Sixty–two patients (45 females, aged 23–81 years) with definite or probable VM (n = 25, 19 definite), MD (n = 29, 17 definite), or showing characteristics of both diseases (n = 8) were included in this study. Diagnostic workup included neurotologic assessments including video-oculography (VOG) during caloric stimulation and head-impulse test (HIT), ocular and cervical vestibular evoked myogenic potentials (o/cVEMP), pure tone audiometry (PTA), as well as iMRI. EH's degree was assessed visually and via volumetric quantification using a probabilistic atlas-based segmentation of the bony labyrinth and volumetric local thresholding (VOLT).Results: Although a relevant number of VM patients reported varying auditory symptoms (13 of 25, 52.0%), EH in VM was only observed twice. In contrast, EH in VM-MD was prevalent (2/8, 25%) and in MD frequent [23/29, 79.3%; χ2(2) = 29.1, p &lt; 0.001, φ = 0.7]. Location and laterality of EH and neurophysiological testing classifications were highly associated (Fisher exact test, p &lt; 0.005). In MD, visual semi-quantitative grading and volumetric quantification correlated highly to each other (rS = 0.8, p &lt; 0.005, two-sided) and to side differences in VOG during caloric irrigation (vestibular EH ipsilateral: rS = 0.6, p &lt; 0.05, two-sided). In VM, correlations were less pronounced. VM-MD assumed an intermediate position between VM and MD.Conclusion: Cochlear and vestibular hydrops can occur in MD and VM patients with auditory symptoms; this suggests inner ear damage irrespective of the diagnosis of MD or VM. The EH grades often correlated with auditory symptoms such as hearing impairment and tinnitus. Further research is required to uncover whether migraine is one causative factor of EH or whether EH in VM patients with auditory symptoms suggests an additional pathology due to MD.