Possible Use of Non-purine Selective Xanthine Oxidoreductase Inhibitors for Prevention of Exercise-induced Acute Kidney Injury Associated with Renal Hypouricemia.

Exercise-induced acute kidney injury (EIAKI) is frequently complicated with renal hypouricemia (RHUC). In patients with RHUC, limiting anaerobic exercise can prevent EIAKI. However, it is challenging to reduce exercise intensity in athletes. We herein report a 16-year-old Japanese football player with familial RHUC with compound heterozygous mutations in urate transporter 1 (URAT1) who presented with recurrent EIAKI. As prophylaxis (hydration during exercise) could not prevent EIAKI, febuxostat was initiated. EIAKI was not observed for 16 months despite exercising intensively. Hence, non-purine-selective xanthine oxidoreductase inhibitors may decrease the incidence of EIAKI in athletes with RHUC.

Different Clinical Courses of Nephronophthisis in Dizygotic Twins.

Siblings with nephronophthisis occasionally show different clinical courses; however, the reasons for this remain unclear. We herein report cases of nephronophthisis in a pair of dizygotic twins with different clinical courses. The brother developed end-stage kidney disease at 17 years old; however, his sister did not show kidney insufficiency. Kidney biopsies revealed severe tubulointerstitial damage at 14 and 22 years old in the brother and sister, respectively. Both had a homozygous NPHP1 deletion with different heterozygous mutations related to hereditary cystic kidney disease. Since the dizygotic twins were exposed to similar environmental factors, genetic factors may have influenced their clinical course more strongly than environmental factors.

Evaluation of a quantitative PCR-based method for chimerism analysis of Japanese donor/recipient pairs.

Chimerism analysis is a surrogate indicator of graft rejection or relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Although short tandem repeat PCR (STR-PCR) is the usual method, limited sensitivity and technical variability are matters of concern. Quantitative PCR-based methods to detect single nucleotide polymorphisms (SNP-qPCR) are more sensitive, but their informativity and quantitative accuracy are highly variable. For accurate and sensitive chimerism analysis, a set of KMR kits (GenDx, Utrecht, Netherlands), based on detection of insertions/deletions (indels) by qPCR, have been developed. Here, we investigated informativity and validated the accuracy of KMR kits in Japanese donor/recipient pairs and virtual samples of DNA mixtures representative of Japanese genetic diversity. We found that at least one recipient-specific marker among 39 KMR-kit markers was informative in all of 65 Japanese donor/recipient pairs. Moreover, the percentage of recipient chimerism estimated by KMRtrack correlated well with ratios of mixed DNA in virtual samples and with the percentage of chimerism in HSCT recipients estimated by STR-PCR/in-house SNP-qPCR. Moreover, KMRtrack showed better sensitivity with high specificity when compared to STR-PCR to detect recipient chimerism. Chimerism analysis with KMR kits can be a standardized, sensitive, and highly informative method to evaluate the graft status of HSCT recipients.

Role of tumor-infiltrating CD11b+ antigen-presenting cells in the progression of gastric cancer.

BACKGROUND: Tumor-infiltrating antigen-presenting cells (APCs), involving tumor-associated macrophages and tumor-infiltrating dendritic cells, play an important role in tumor immunity and immune escape. The aim of this study was to determine whether tumor infiltrating CD11b(+) APCs may affect tumor progression and clinical outcome. METHODS: The immunohistochemical analysis was used to evaluate the expression of CD11b, FOXP3, and CD8 in 214 gastric cancer tissues. Concentrations of immunosuppressive cytokines in medium conditioned by gastric cancer cells were measured by enzyme-linked immunosorbent assay. Effects of addition of tumor-conditioned media on CD11c(+) cells were examined by flow cytometry. RESULTS: Almost all tumor-infiltrating CD11b(+) cell expressed CD11c and was considered to be APCs. High CD11b(+) cell infiltration was significantly correlated with huge tumor, positive venous invasion, lymph node metastasis, and tumor, node, metastasis stage. Patients with high CD11b(+) cell infiltration had a poorer surgical outcome than those with low CD11b infiltration. Multivariate analysis revealed that CD11b(+) cell infiltration was one of the independent prognostic factors. Tumor-conditioned medium obtained from several gastric cancer cell lines contained immunosuppressive cytokines, transforming growth factor-beta, interleukin-10, and vascular endothelial growth factor. The addition of tumor-conditioned medium decreased the expression of major histocompatibility complex-II and increased the expression of CD11b and programmed death ligand 2 on CD11c(+) APCs. Infiltration of CD11b(+) cells significantly correlate with the degree of FOXP3(+) cell infiltration but not with CD8(+) cell infiltration. CONCLUSIONS: Tumor-infiltrating CD11b(+) APCs affected local tumor cell-immune cell interactions and correlated to the poor prognosis of the patients with gastric cancer.

Intranodal lymphangiogenesis precedes development of lymph node metastasis and accelerates progression of gastric cancer.

INTRODUCTION: Peritumoral lymphangiogenesis is significantly correlated with lymph node metastasis and poor prognosis in various cancers. However, there are few reports concerning the role of intranodal lymphangiogenesis in lymphatic metastasis. The aim of this study was to examine the association of lymphangiogenesis in regional lymph nodes with the progression of gastric cancer. MATERIALS AND METHODS: Lymphatic vessel density (LVD) was immunohistochemically estimated in 1,596 lymph nodes from 52 patients who underwent gastrectomy. RESULTS: Intranodal LVD was significantly correlated with the size of metastasis and the progression of cancer. Patients in the high LVD group had significantly poorer prognosis relative to patients in the low LVD group. Furthermore, expression of VEGF-C mRNA was significantly up-regulated in lymph nodes of pathological node positive patients compared to node negative patients. DISCUSSION: Thus, intranodal lymphangiogenesis was correlated with nodal metastasis and poor prognosis of patients with gastric cancer. Lymphangiogenesis in regional lymph nodes plays an early role in spreading of tumor cells through the lymphatic system to distant organs in gastric cancer.

[Our experience of eribulin treatment in advanced breast cancer].

The clinical outcomes, including adverse events, in 40 advanced breast cancer patients treated with eribulin were analyzed to confirm the effectiveness and safety of this treatment. The objective response rate (ORR) in patients was 35.0%. The median overall survival and time to treatment failure (TTF) in these patients was 479 and 63 days, respectively. Cases wherein eribulin was used as early-line treatment experienced significantly longer TTF compared to the cases wherein eribulin was used as late-line treatment; however, there was no difference in this value according to the breast cancer subtype. Moreover, subtype analysis revealed no significant difference in adverse events. We observed no difference in the benefit or tolerability of eribulin treatment among different breast cancer subtypes. However, our results suggest that a significant therapeutic effect can be expected when using eribulin as early-line treatment.

[Effectiveness of eribulin chemotherapy for squamous cell carcinoma of the breast].

The patient was a 40-year-old woman who was aware of a tumor in her left breast that was gradually increasing in size. Ultrasonography revealed a hypoechoic mass with a skin cyst, approximately 3 cm in size, in the C area of the left breast. Core needle biopsy indicated estrogen receptor (ER) -negative, progesterone receptor (PR) -negative, and human epidermal growth factor receptor 2 (HER2) -negative squamous cell carcinoma. Overall examination did not indicate distant metastasis. A diagnosis of T4bN2aM0, stage IIIB triple-negative left breast cancer was made. Eribulin was administered at a dose of 1.4 mg/m2. The effect of eribulin was considered to be long-term stable disease( long-term SD). The patient did not experience severe adverse events during treatment. After 24 weeks of eribulin treatment, mastectomy of the left breast with axillary lymph node dissection was performed. At present, 1 year after surgery, the patient is alive with no recurrence. We conclude that eribulin chemotherapy is useful for the treatment of patients with squamous cell carcinoma of the breast.

[Case of a patient with inflammatory breast cancer who responded to preoperative chemotherapy with paclitaxel plus bevacizumab and could subsequently undergo surgery].

A 58-year-old woman observed swelling in her left breast a few weeks prior to presentation. Rigidity in the D area, breast warmth, swelling, and a peau d'orange appearance in the whole left breast was observed. She was diagnosed with inflammatory breast cancer (luminal A type) T4dN2M0, Stage IIIB. The patient underwent primary systemic therapy with 7 courses of FEC. Following FEC treatment, the disease was stable. We subsequently administered 4 courses of bevacizumab plus paclitaxel combination therapy. The patient exhibited a partial response to FEC chemotherapy. Thereafter, a left mastectomy with level II axillary lymph node dissection was performed. At present, 1 year after surgery, the patient is alive with no recurrence. We conclude that the combination therapy of bevacizumab plus paclitaxel is a useful treatment for inflammatory breast cancer.

[Usefulness of bevacizumab combination chemotherapy for advanced breast cancer].

Bevacizumab combination chemotherapy prolongs progression-free survival but not overall survival in patients with advanced breast cancer. Here, we report our experience with bevacizumab plus paclitaxel treatment in our department. We believe that this regimen confers some benefit to a patient's quality of life. Nineteen patients with inoperable, metastatic, or recurrent breast cancer were treated with bevacizumab plus paclitaxel. The median age was 55 years; all patients were females. Of the 19 patients, 14, 1, and 4 had luminal A, luminal B, and triple-negative type tumors, respectively. The response rate was 63%: partial response (PR) was obtained in 12 patients, stable disease (SD) in 5 patients, and progressive disease( PD) in 2 patients. Adverse events of Grade 3 or more were high blood pressure( 4 patients), peripheral neuropathy (1 patient), and neutropenia (9 patients). All side effects could be tolerated. There was a high rate of response to bevacizumab plus paclitaxel chemotherapy. We believe that this chemotherapy is useful in patients with more advanced breast cancer in whom a high response rate is required.

[Day surgery of early breast cancer treated with breast-conserving operation following sentinel lymph node navigation biopsy under local anesthesia].

In the early stages of breast cancer when axillary lymph node dissection is avoidable, we performed same day surgery with a breast-conserving operation following sentinel lymph node navigation biopsy under local anesthesia. Initial sentinel lymph node biopsy under local anesthesia is performed to avoid false-negative sentinel lymph node metastasis. Resected sentinel lymph nodes were examined in fixed sections by hematoxylin-eosin staining and immunohistochemistry. The enrolled subjects were 20 patients with breast cancer whose diagnoses were confirmed before treatment. Two (10.0%) patients had metastasis.

[Four cases of meningeal metastasis originating from breast cancer].

Carcinomatous meningitis due to breast cancer is comparatively rare in Japan. Here, we report 4 cases of carcinomatous meningitis due to breast cancer. Meningeal metastasis was present in only 1 of the 4 cases, and the other 3 cases were associated with brain metastasis. Meningeal metastasis frequently causes symptoms associated with intracranial hypertension. Gadolinium-enhanced magnetic resonance imaging and cerebrospinal fluid cytology were useful for the diagnosis of meningeal metastasis. Multidisciplinary therapy, such as radiation and chemotherapy, was performed. Two of the 4 patients were treated with combined intrathecal administration of methotrexate and whole brain radiation. The quality of life was improved by multidisciplinary therapy.

[Needle biopsy using a Monopty Biopsy Instrument for the accurate diagnosis of thyroid cancer].

Aspiration biopsy cytology (ABC) is commonly performed for the diagnosis of thyroid tumor. Because ABC may not provide sufficient tissue for pathological diagnosis, we performed needle biopsy using a Monopty Biopsy Instrument for the accurate diagnosis of thyroid cancer. Furthermore, it is difficult to safely perform a core needle biopsy (CNB) for the diagnosis of breast cancer in the thyroid gland region. In this study, we evaluated the feasibility of using a Monopty Biopsy Instrument as an alternative to conventional ABC or CNB for the biopsy-based diagnosis of thyroid cancer. Twenty patients with clinically suspected thyroid cancer were enrolled, and all patients were thoroughly examined. Seven cases of thyroid cancer were diagnosed, of which 5 cases were papillary carcinoma and 2 were undifferentiated carcinoma.