Carcinomas of the renal pelvis associated with smoking and phenacetin abuse: p53 mutations and polymorphism of carcinogen-metabolising enzymes

Phenacetin abuse and smoking are established risk factors for transitional cell carcinomas of the urinary tract. In the present study, we analysed exposure and the clinical course of patients who underwent nephrectomy for transitional cell carcinoma of the renal pelvis. PCR-SSCP of archival, paraffin-embedded histological sections followed by direct DNA sequencing revealed that 29 of 89 (33%) renal pelvic carcinomas contained a p53 mutation. Double mutations were found in 4 tumours and triple mutations in 1 tumour. The incidence of p53 mutations was significantly higher in tumours with grades 3 and 4 than in those with grades 1 and 2 and higher in invasive than in non-invasive tumours. Furthermore, patients with carcinomas carrying a p53 mutation showed poorer survival than those without mutation. The type of p53 mutation in renal pelvic carcinomas was similar to that reported for bladder cancer, G:C→A:T transition mutations being most frequent (45%, 33% of these at CpG sites), followed by G:C→T:A and G:C→C:G transversions. The incidence and type of p53 mutation did not differ significantly in patients with a history of phenacetin abuse, smoking or neither of these habits. This was also true for G:C→T:A transversions (17.5% of mutations), which are considered typical of smoking-induced carcinomas at other sites, e.g., lung, oral cavity and oesophagus. Our results indicate that the frequency and pattern of p53 mutations are similar in transitional cell carcinomas of the bladder and the renal pelvis and do not reflect exposure to phenacetin and/or smoking. The frequency of genetic polymorphism in genes coding for carcinogen-metabolising enzymes (CYP1A1, NAT1, GSTT1 and GSTM1) was also independent of exposure. Although the sample size of our study does not allow definite conclusions, these data are compatible with chronic tissue damage as a causative factor in the evolution of urothelial carcinomas rather than pointing to a direct mutagenic effect of phenacetin and tobacco-specific carcinogens. Int. J. Cancer (Pred. Oncol.) 79:531–536, 1998.© 1998 Wiley-Liss, Inc.     

Microsatellite instability in sporadic human breast cancers

Human breast-cancer specimens from 100 patients were analyzed for microsatellite instability (referred to as replication error; RER) at 12 genomic loci on 7 chromosomes, and results were correlated with clinicopathologic characteristics. In 42 of 100 breast-cancer patients, we investigated whether RER was associated with the amplification of oncogenes and/or suppression of tumor-suppressor genes. Of the 100 patients, 8 (8%) were RER-positive at one or more chromosomal loci. The majority of RER-positive patients had early-stage disease with ER-positive tumors, suggesting that RER occurs early in breast tumorigenesis. However, no significant correlation was observed between RER and oncogenes or tumor-suppressor genes. Thus, the mechanism of RER in sporadic human breast cancer may be independent of the multi-step carcinogenesis caused by the alterations of oncogenes and tumor-suppressor genes. © 1996 Wiley-Liss, Inc.     

Magnetic Resonance Imaging Grading System for Preoperative Diagnosis of Leiomyomas and Uterine Smooth Muscle Tumors

Study Objective

To evaluate a new magnetic resonance imaging (MRI) grading system for preoperative differentiation between benign and variant-type uterine leiomyomas including smooth muscle tumors of uncertain malignant potential (STUMPs).

Intrahepatic subcapsular biloma after endoscopic retrograde cholangiopancreatography treated by endoscopic biliary drainage

Several major complications from endoscopic retrograde cholangiopancreatography (ERCP), including pancreatitis, cholangitis, and hemorrhage have been discussed in detail; however, a few uncommon but severe complications have been reported. We encountered an unusual case of post-ERCP intrahepatic subcapsular biloma. An 89-year-old woman with a 25-mm mass located at the hepatic hilum, suggestive of cholangiocarcinoma, underwent ERCP which demonstrated complete stricture of the common hepatic duct. Subsequently, two plastic stents were placed from the common bile duct to the right and left intrahepatic branches. On day 3, serum inflammatory markers were elevated and computed tomography revealed a large subcapsular fusiform fluid collection in the right liver, consistent with biloma. On day 6, the biloma ruptured and 500 ml of biliary ascites were removed. On day 8, endoscopic nasobiliary drainage via the right intrahepatic branch was performed because of recurrence of biliary ascites. After the procedure, 150 ml of bile was collected through the drain every day and no ascites recurred. We believe that minor injury to the right intrahepatic bile duct due to guidewire manipulation caused the biloma. Biloma may become apparent several days after ERCP, and endoscopic biliary drainage placement adjacent to the bile duct rupture site can stop bile leakage.     

Excitotoxicity in encephalopathy associated with STEC O-157 infection

Cytokines play an important role in the pathogenesis of the severe complications of Shiga toxin-producing Escherichia coli (STEC) infection, such as hemolytic uremic syndrome (HUS) and acute encephalopathy. A 3-year-old boy with acute encephalopathy associated with STEC O-157 HUS showed increased levels of IL-6 and IL-10, which normalized after methylprednisolone pulse therapy, and additionally exhibited a transient increase of glutamine on MR spectroscopy. This finding suggests that excitotoxicity, in addition to hypercytokinemia, may play an important role in the pathogenesis of HUS encephalopathy.     

Successful hemispherotomy in two refractory epilepsy patients with cerebral hemiatrophy and contralateral EEG abnormalities

We describe two cases of refractory epilepsy with cerebral hemiatrophy and contralateral electroencephalographic (EEG) abnormalities, in which hemispherotomy of the atrophic hemisphere effectively controlled seizures. Case 1 was a 5-year-1-month-old girl with refractory bilateral asymmetrical tonic posturing seizures predominantly in the right arm. Magnetic resonance imaging showed left porencephaly corresponding to a left middle cerebral artery infarction. Case 2 was a 3-year-8-month-old boy with refractory bilateral asymmetrical tonic posturing seizures predominantly in the right arm due to atrophy of the left cerebral hemisphere after septic meningitis. Both patients had right hemiparesis and was incapable of pinching by the right hand. Contralateral interictal and ictal EEG abnormalities were observed. Interictal ^99mTc-ethyl cysteinate dimer (^99mTc-ECD) single photon emission computed tomography (SPECT) showed hypoperfusion and ictal ^99mTc-ECD-SPECT showed hyperperfusion within the left cerebral hemisphere. Left hemispherotomy was performed. Cases 1 and 2 remained seizure-free at the last follow-up 18?months and 15?months, respectively, after surgery, and contralateral interictal EEG abnormalities disappeared. In patients with cerebral hemiatrophy and contralateral EEG abnormalities, epilepsy surgery may be considered when the laterality of seizure semiology, functional imaging findings and motor deficits were concordant with the atrophic side. Ictal SPECT is effective to confirm the epileptogenic hemisphere.     

Management of diabetic macular edema in Japan: a review and expert opinion

Diabetic retinopathy is a frequent cause of visual impairment in working-age adults (≥ 30 years) and in Japan is most commonly observed in those aged 50–69 years. Diabetic macular edema (DME) is one of the main causes of vision disturbance in diabetic retinopathy, which is a clinically significant microvascular complication of diabetes. Anti-vascular endothelial growth factor (VEGF) therapy is becoming the mainstay of treatment for DME. However, to achieve sustained long-term improvement in visual acuity, conventional laser photocoagulation, vitrectomy and steroid therapy are also expected to play a role in the treatment of DME. This review summarizes the epidemiology and pathology of diabetic retinopathy and DME, evaluates the findings regarding the diagnosis and treatment of DME, and underscores the importance of systemic management of the disease in the context of the current health care situation in Japan. Finally, the unmet needs of patients with DME and prospects for research are discussed. The weight of evidence suggests that it is important to establish a multipronged treatment strategy centered on anti-VEGF therapy.     

Enhanced neurogenesis and possible synaptic reorganization in the piriform cortex of adult rat following kainic acid‐induced status epilepticus

Epileptic seizure has been reported to enhance adult neurogenesis and induce aberrant synaptic reorganization in the human dentate gyrus in the hippocampal formation. However, adult neurogenesis in the extrahippocampal regions has not been well studied. To investigate seizure‐enhanced neurogenesis in the extrahippocampal regions, we performed histological and immunohistochemical as well as western blot analyses on the cerebrum of Sprague–Dawley rats (n = 51, male, 7 weeks old, body weight 250–300 g) treated with intraperitoneal injection of kainic acid (KA, 10 mg/kg) to induce status epilepticus (SE) (n = 36) or normal saline solution (n = 15) followed by 5′‐bromo‐2‐deoxyuridine (BrdU) injection to label newborn cells. Even though severe neuronal damage was found in the piriform cortex of rats having SE, immunohistochemistry for double cortin (DCX) revealed an increase in the number of immature neurons in the piriform cortex. Double immunofluorescence staining demonstrated that DCX‐positive cells in the piriform cortex were positive for both BrdU and neuronal nuclear antigen. Immunohistochemistry and western blotting revealed increased expressions of synaptophysin and postsynaptic density protein 95 in the piriform cortex of rat having SE. These results suggested the enhanced neurogenesis and possible synaptic reorganization in the piriform cortex of the KA‐treated rat.