A case of aortoduodenal fistula following radiotherapy of retroperitoneal metastatic disease

A new case of aortoduodenal fistula was added to the five cases previously reported in the literature, in which malignancy and/or its treatments could be implicated. This 67 year-old woman, six years previously had been placed on a therapy including irradiation on the pelvis for cancer of uterine cervix. For this time she underwent a radiotherapy completed in a total dose of 55.6 Gy combined with hyperthermia and chemotherapy for retroperitoneal metastatic disease with excellent response. Three months later she had hematemesis followed by melena and deteriorated to hemorrhagic shock. Emergent aortography detected contrast extravasation from the aorta with subsequent opacification of the duodenum, and immediate intraaortic balloon occlusion was done, but she died soon thereafter. Postmortem examination revealed the fistula from the aorta just above the bifurcation to a 2 by 1.5 cm. area of the posterior wall of the third portion of the duodenum. Accentuated arteriosclerosis in locally irradiated portion of the aorta, obstruction of small arteries from organized thrombus and hyaline necrosis in the wall of the fistulous tract were defined without evidence of tumor invasion. Based upon the findings of the patient reported herein, radiation might be another possible etiologic factor in aortoduodenal fistula, as well as tumor invasion per se.     

Clinical and arthroscopic findings of acute anterior cruciate ligament tears of the knee

Clinical, arthrographic, and arthroscopic findings in 53 patients with acutely torn anterior cruciate ligaments (ACLs) were documented. Arthroscopy and instability tests under anesthesia were performed on all patients within 2 weeks after the initial injury. Twenty-three patients complained of extension blocks, and localized tenderness on the medial side was revealed in 26 patients at the initial examination. Aspiration from joints exhibited hemarthrosis in 52 patients. Arthroscopy revealed ACL ruptures in all patients. Four Segond's fractures, 26 meniscus tears (8 medial and 18 lateral), 1 osteochondral fracture, and 19 medial collateral ligament ruptures were revealed. Arthroscopy detected only 1 of the 5 ruptures of the posteromedial corner of the medial meniscus, which were noted on arthrography. Three ACL stumps were protruding among the femorotibial joint, which seemed to be restricting full extension. Statistical analysis showed that tenderness on the medial side was not revealed more frequently in knees with medial collateral ligament injuries than in the others. The volume of aspirated fluids in knees with no leakage in arthrography significantly increased over those with leakages (p < 0.05). Diagnosis of ACL injuries should be completed by clinical, arthrographic, and arthroscopic examinations.     

Intratumoral ethanol injection for malignant tracheobronchial lesions: a new bronchofiberscopic procedure

We performed intratumoral ethanol injection via a flexible bronchofiberscope in 13 patients with malignant tracheobronchial lesions in order to evaluate its effects on airway dilatation and hemostasis. The results obtained are described below. Immediately after intratumoral injection of ethanol, bronchofiberscopic findings revealed that the tumor turned faintly white, there was a little regression of tumor, and a promising effect was demonstrated on patients with bleeding from tumors. The injected tumor turned necrotic within several days, and histological examination revealed no viable tumor cells in necrotic tissues. The histological anti-tumor effect of ethanol was also demonstrated in experiments with nude mice. This endoscopic treatment was very effective in polypoid tumor protruding into the tracheobronchial lumen, but ineffective in the case of compressed stenosis or obstruction. In conclusion, intratumoral injection of ethanol is considered to be a promising endoscopic treatment for malignant tracheobronchial lesions.     

Phosphorylation of podocalyxin (Ser415) Prevents RhoA and ezrin activation and disrupts its interaction with the actin cytoskeleton

Podocalyxin (PC) is a polysialylated, anti-adhesin that is essential for maintaining foot process architecture and the integrity of the glomerular filtration barrier. We showed previously that PC is firmly attached to the actin cytoskeleton through ezrin, that in puromycin aminonucleoside (PAN)-mediated nephrosis the PC-ezrin-actin complex is disrupted, and that PC is uncoupled from actin. However, the precise mechanisms involved remained unknown. Here we show that detachment of PC from actin is regulated by phosphorylation of PC. PC is hyperphosphorylated at serines in PAN- and protamine sulfate (PS)-treated rat glomeruli. We determined that PC is a substrate of PKC and that the site of phosphorylation is Ser415, located within the juxtamembrane, ezrin-binding domain of the cytoplasmic tail of PC. Mutation of Ser415 to the phosphomimetic residues Glu (S415E) or Asp (S415D) interfered with direct binding of the PC cytoplasmic tail to ezrin in vitro. Moreover, stable expression of a phosphomimetic (S415E) PC mutant but not the WT or the phosphorylation-deficient (S415A) PC mutant, disrupted PC-ezrin-actin interaction, failed to activate RhoA, and the cytoskeletal linker, ezrin, remained inactive. Our data indicate that phosphorylation of PC at Ser415 prevents attachment of PC and ezrin to actin and highlights the strategic position of Ser415 and direct binding of PC to ezrin in regulating podocyte foot process architecture.     

Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome

Mutations of the gene encoding the α2 subunit of the neuronal sodium channel, SCN2A, have been found in benign familial neonatal-infantile seizures (BFNIS). In Dravet syndrome, only one nonsense mutation of SCN2A was identified, while hundreds of mutations were found in the paralogue gene, SCN1A, which encodes the α1 subunit. This study examines whether SCN2A mutations are associated with Dravet syndrome. We screened for mutations of SCN1A, SCN2A and GABRG2 (the gene encoding γ2 subunit of the GABA_A receptor) in 59 patients with Dravet syndrome and found 29 SCN1A mutations and three missense SCN2A mutations. Among the three, one de novo SCN2A mutation (c.3935G>C: R1312T) identified in a patient was thought to affect an arginine residue in a voltage sensor of the channel and hence, to be pathogenic. This finding suggests that both nonsense mutations and missense SCN2A mutations cause Dravet syndrome.     

Complications in the central nervous system during chemotherapy for childhood acute lymphoblastic leukemia: JACLS ALL-02 study

We evaluated central nervous system (CNS) complications treated under the ALL-02 protocol of the Japan Association of Childhood Leukemia Study (JACLS) from April 2002 to March 2005. According to NCI Toxicity Criteria, 17 events of grade 3 and 4 CNS complications were reported in 15 out of 541 patients. Out of these CNS complications, leukoencephalopathy was seen in 5 patients; seizure in 5; cerebrovascular disease in 3; conscious disturbance in 2; and hypertensive encephalopathy and reversible posterior leukoencephalopathy syndrome in one patient each. The complications were intensively observed during induction therapy and the last of the early phase chemotherapy. The protocol treatment was stopped or modified in most patients after CNS complications. MRI imaging demonstrated no improvement in one patient with leukoencephalopathy who developed an isolated CNS relapse, while other patients were alive and remain in their first complete remission without any neurological sequelae. Further studies will be required to analyze risk factors for CNS complications during chemotherapy not accompanied by irradiation and to establish alternative treatments after the appearance of such CNS complications.     

Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti‐topoisomerase I‐positive systemic sclerosis‐associated interstitial lung disease

Systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) is the most frequent cause of death for SSc but there is still no sufficient treatment available. Although cyclophosphamide (CYC) therapy is a common treatment which has shown statistical efficacy against SSc‐ILD to date, its effects are temporary and not enough. Rituximab (RTX), the anti‐CD20 monoclonal antibody, has recently shown efficacy in many autoimmune diseases. In SSc‐ILD, RTX is also considered to be one of the novel treatment candidates. However, studies of SSc‐ILD in Japanese treated with RTX have only a few case reports. Therefore, in this study, we retrospectively compared nine patients treated with RTX and 30 patients treated with CYC to investigate the efficacy of RTX treatment for Japanese anti‐topoisomerase I‐positive SSc‐ILD patients. At the 24‐month evaluation, the improvement rates of percent predicted of forced vital capacity and percent predicted of diffusing capacity of the lung carbon monoxide in the RTX‐treated group were significantly higher than those in the CYC‐treated group (20.6 ± 8.8% vs 1.1 ± 3.9%; P < 0.05 and 34.0 ± 6.0% vs ?1.5 ± 2.8%; P < 0.01, respectively). In addition, skin thickness scores also showed a marked improvement from 13.5 points before the start of treatment to 5.8 points after 24 months by RTX therapy (P < 0.05). These results suggest that RTX treatment is more effective for Japanese SSc‐ILD patients than CYC treatment. In the future, it is expected that large‐scale clinical trials will show the usefulness of RTX treatment for SSc‐ILD.