Diagnostic criteria for atypical hemolytic uremic syndrome proposed by the joint committee of the Japanese society of nephrology and the Japan pediatric society

Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of ~25 %, and with ~50 % of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.     

Common variants at 1p36 are associated with superior frontal gyrus volume

The superior frontal gyrus (SFG), an area of the brain frequently found to have reduced gray matter in patients with schizophrenia, is involved in self-awareness and emotion, which are impaired in schizophrenia. However, no genome-wide association studies of SFG volume have investigated in patients with schizophrenia. To identify single-nucleotide polymorphisms (SNPs) associated with SFG volumes, we demonstrated a genome-wide association study (GWAS) of gray matter volumes in the right or left SFG of 158 patients with schizophrenia and 378 healthy subjects. We attempted to bioinformatically ascertain the potential effects of the top hit polymorphism on the expression levels of genes at the genome-wide region. We found associations between five variants on 1p36.12 and the right SFG volume at a widely used benchmark for genome-wide significance (P<5.0 × 10⁻⁸). The strongest association was observed at rs4654899, an intronic SNP in the eukaryotic translation initiation factor 4 gamma, 3 (EIF4G3) gene on 1p36.12 (P=7.5 × 10⁻⁹). No SNP with genome-wide significance was found in the volume of the left SFG (P>5.0 × 10⁻⁸); however, the rs4654899 polymorphism was identified as the locus with the second strongest association with the volume of the left SFG (P=1.5 × 10⁻⁶). In silico analyses revealed a proxy SNP of rs4654899 had effect on gene expression of two genes, HP1BP3 lying 3′ to EIF4G3 (P=7.8 × 10⁻⁶) and CAPN14 at 2p (P=6.3 × 10⁻⁶), which are expressed in moderate-to-high levels throughout the adult human SFG. These results contribute to understand genetic architecture of a brain structure possibly linked to the pathophysiology of schizophrenia.     

Rectal Cancer With Disseminated Carcinomatosis of the Bone Marrow: Report of a Case

We report a rare case of disseminated carcinomatosis of the bone marrow from rectal cancer with disseminated intravascular coagulation (DIC). A 65-year-old man was admitted with melena and low back pain at rest. X-ray examination showed rectal cancer with multiple bone metastases. Laboratory examination showed severe anemia and DIC. Histologic examination showed disseminated carcinomatosis of the bone marrow. The DIC was considered to be caused by disseminated carcinomatosis of the bone marrow from rectal cancer, and we immediately started treatment with anti-DIC therapy and anticancer chemotherapy with the modified FOLFOX6 regimen (mFOLFOX6). After some response to therapy, the patient''s general condition deteriorated, and he died 128 days after admission. This is the first English report showing disseminated carcinomatosis of the bone marrow from colorectal cancer treated with mFOLFOX6.Key words: Bone marrow neoplasms, Rectal neoplasms, Disseminated intravascular coagulationBone metastases diffusely invading the bone marrow with disseminated intravascular coagulation (DIC) and microangiopathic hemolytic anemia (MHA) tend to accompany solid tumors; this condition is called disseminated carcinomatosis of the bone marrow,¹ and it is associated with an extremely poor prognosis. Among solid tumors, DIC is most commonly associated with breast cancer, prostate cancer, and lung cancer^2,3; carcinomatosis arising from colorectal cancer is rare.Herein we report on a patient with disseminated carcinomatosis of the bone marrow with rectal cancer who developed acute DIC and was treated with a modified FOLFOX6 regimen (mFOLFOX6). We also review 11 similar previously reported cases.^4–10     

Exploratory Analysis to Find Unfavorable Subset of Stage II Gastric Cancer for Which Surgery Alone Is the Standard Treatment; Another Target for Adjuvant Chemotherapy

The aim of the present study was to explore the unfavorable subset of patients with Stage II gastric cancer for whom surgery alone is the standard treatment (T1N2M0, T1N3M0, and T3N0M0). Recurrence-free survival rates were examined in 52 patients with stage T1N2-3M0 and stage T3N0M0 gastric cancer between January 2000 and March 2010. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model. The recurrence-free survival (RFS) rates of the patients with stages T1N2, T1N3, and T3N0 cancer were 80.0, 76.4, and 100% at 5 years, respectively. The only significant prognostic factor for the survival rates of the patients with stage pT1N2-3 cancer measured by univariate and multivariate analyses was pathological tumor diameter. The 5-year RFS rates of the patients with stage pT1N2-3 cancer were 60.0%, when the tumor diameters measured <30 mm, and 88.9% when the tumor diameters measured >30 mm (P = 0.0248). These data may suggest that pathological tumor diameter is associated with poor survival in patients with small T1N2-3 tumors. Because our study was a retrospective single-center study with a small sample size, a prospective multicenter study is necessary to confirm whether small tumors are risk factor for the RFS in T1N2-3 disease.Key words: Gastric cancer, Stage II, Adjuvant chemotherapyEvery year, more than 934,000 people develop gastric cancer worldwide. After lung cancer, gastric cancer is the second most frequent cancer-related cause of death.¹ Complete resection is essential to cure gastric cancer. Patients with stage II or stage III gastric cancer often develop tumor recurrence, even after complete curative resections.In 2007, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) phase III trial demonstrated that S-1 is effective as adjuvant chemotherapy in Japanese patients who have undergone curative D2 gastrectomy for advanced gastric cancer.² In general, patients eligible for ACTS-GC were those diagnosed with pathological stages II and III. However, patients classified with pathological (p) stages T1N2M0, T1N3M0, and T3N0M0—which are classified as part of stage II—were excluded from the ACTS-GC trial. Because in the prior phase III studies comparing surgery alone and adjuvant chemotherapy, patients with stages T1N+ and T2-3/N0 cancer had excellent prognoses with 5-year overall survival (OS) rates of more than 80% from surgery alone,^3,4 these patients were excluded from receiving adjuvant chemotherapy. Japanese Gastric Cancer Association (JGCA) guidelines clearly state that the standard treatment for these patients is surgery alone.⁵Therefore, patients with stage II gastric cancer have been divided into two groups: one for whom the standard treatment is surgery alone, and the other for whom the standard treatment is surgery and adjuvant chemotherapy with S-1. Before the advent of ACTS-GC, survival rates were poorer in the latter group than in the former. However, treatment with adjuvant chemotherapy with S-1 has reversed this trend. Now, patients in the latter group receiving S-1 adjuvant chemotherapy have 5-year OS rates of 84.2%.⁶ Therefore, it may be old rationale that dictates that patients in the former group should be excluded from receiving adjuvant chemotherapy, because the 5-year OS rates are now more than 80% by S-1 adjuvant chemotherapy in the latter group. Five-year OS rates of 80% would not be obtained by surgery alone. Among those patients with stage II gastric cancer assigned to the surgery alone group, some may have a poor prognosis and be good candidates for adjuvant chemotherapy. The aim of the present study was to explore the unfavorable subset of patients among those with stage II gastric cancer for whom surgery alone is the standard treatment (T1N2M0, T1N3M0, and T3N0M0).