Crescentic glomerulonephritis associated with renal cell carcinoma after cancer immunotherapy

A 59 year-old woman showed rapidly progressive glomerulonephritis during immunotherapy for metastatic renal cell carcinoma. She received unilateral nephrectomy and cytotoxic T lymphocyte (CTL) therapy for the treatment of retroperitoneal lymph node metastasis of renal cell carcinoma. With CTL therapy, her retroperitoneal lymph node mass decreased in size. One year after the third round of CTL therapy, her serum creatinine was increased and massive proteinuria occurred. Her renal biopsy specimen revealed necrotizing and crescentic glomerulonephritis with immune complex deposition. Her retroperitoneal lymph node mass continued to decrease in size. Consequently, for the purpose of avoiding interfering with the CTL therapy, we performed double filtration plasmapheresis (DFPP) monotherapy for removal of immune complexes without using immunosuppressive drugs or prednisolone. After 24 sessions of DFPP, her serum IgG was reduced from 3,942 mg/dL to 2,400 mg/dL, and proteinuria (from 9.0 g/day to 0.9 g/day) and renal function (serum creatinine; from 5.6 mg/dL to 2.2 mg/dL) also improved. However, 3 months after the final DFPP, she expired due to perforation of the colon. The autopsy sample of the kidney showed that most of the glomeruli were obsolescent, but immunoglobulin depositions were reduced and necrotizing lesions were diminished. In the patients with RPGN associated with renal cell carcinoma, renal functional recovery has not been observed upon immunosuppressive treatment. Consequently, plasmapheresis is considered to be one of the effective and safe methods for patients with this association. We also discuss previous reports of RPGN associated with renal cell carcinoma, or RPGN after cancer immunotherapy.     

Plate removal in traumatic facial fractures: 13-year practice review

Various complications can result from titanium plate internal fixation, including infection, exposure, pain, cold intolerance, and palpability. The incidence of such complications has become a topic of recent interest with the advent of resorbable plating. We undertook a retrospective review to determine complication rates of titanium fixation in a facial fracture population. Out of 266 patients with operative management of traumatic facial fracture between 1991 and 2004, 135 patients had titanium plate fixation. We evaluated 16 panfacial fractures, 22 zygomatic-orbital complex fractures, 49 midface fractures, and 48 fractures of the mandible. Overall, 33.3% (45/135) of patients had plates removed; 64.4% (29/45) of plate removals were for complications, ie, discomfort, exposure, and infection; 35.6% (16/45) were removed during secondary reconstruction. The most common complication was discomfort related to palpability, cold intolerance, and pain. This constituted 72.4% (21/29) of all plate removals for complications. Higher rates of plate discomfort were noted near the supraorbital, infraorbital, and mental foramina.     

STK15 polymorphism and breast cancer risk in a population-based study

STK15 is considered a potential cancer susceptibility gene owing to its functions in normal cell mitosis. Two common coding region polymorphisms in the gene (F31I and V57I) may affect ubiquitin-dependent degradation and thus the half-life of the encoded protein. There are limited data on the relevance of these polymorphisms to population cancer rates. To examine whether functional variation in STK15 may affect breast cancer risk, we genotyped a large series of incident breast cancer cases (n = 941) and age-matched population controls (n = 830) for the F31I and V57I polymorphisms. Individually, neither the F31I polymorphism [odds ratio (OR) 1.54; 95% confidence interval (CI) 0.96-2.47, comparing 31I with 31F homozygotes] nor the V57I polymorphism (OR 0.92; 95% CI 0.50-1.71, comparing 57I with 57V homozygotes) was significantly associated with breast cancer risk. A relatively common genotype, combining the two polymorphisms (31I-57V/31I-57V, 3% of controls) was related to a significant 2-fold increase in the risk of post-menopausal breast cancer (OR 1.96; 95% CI 1.01-3.79). No interaction was detected between STK15 variants and estrogenic risk factors, although the power of these analyses was limited. These results suggest that STK15 may represent a low penetrance type breast cancer susceptibility gene.     

The antioxidant EPC-K1 ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischaemia

Summary ?Background. Cerebral ischaemia-reperfusion injury is associated with the generation of reactive oxygen species during the early phases of reoxygenation. EPC-K1, a phosphate diester of vitamins C and E, has been reported to possess potent hydroxyl radical scavenging activity. This study was performed to investigate the effectiveness of EPC-K1 in attenuating cerebral ischaemia-reperfusion injury in a rat model of transient focal cerebral ischaemia. Method. We evaluated the efficacy of EPC-K1 by measuring the concentration of cerebral thiobarbituric acid reactive substances (TBARS), an indicator of the extent of lipid peroxidation by free radicals, and infarct size in rats subjected to one hour of cerebral ischaemia and 4, 24, or 72 hours of reperfusion. Findings. EPC-K1 significantly reduced both the cerebral TBARS level and the infarct size in a rat model of transient focal cerebral ischaemia. These results indicate that EPC-K1 administration during the early stages of reperfusion ameliorates ischaemic brain injury by inhibiting lipid peroxidation. Interpretation. This report is the first to describe the protective mechanism of EPC-K1 by measuring both the TBARS level and infarct size in a rat model of transient focal cerebral ischaemia, and may suggest a potential clinical approach for the treatment of ischaemic cerebrovascular disease. Published online June 11, 2003     

Virtual pancreatoscopy of pancreatic cancer

BACKGROUND/AIMS: Virtual endoscopy is a new method of diagnosis using computer processing of three-dimensional images data sets. However, there are few reports about the clinical application of virtual endoscopy for the pancreas. In this study, we evaluated the feasibility of surface-rendered magnetic resonance virtual endoscopy for pancreatic cancer. METHODOLOGY: Twenty-six cases of pancreatic cancer were studied. Fifteen patients had pancreatic head cancer, 7 had pancreatic body cancer, and 4 had pancreatic tail cancer. Twelve patients underwent surgical resection of the pancreas. Magnetic resonance imaging data were acquired with a 1.5-T clinical imager (Signal.5; GE Medical Systems, USA). We used a multislab single-shot fast spin-echo sequence. Section thickness was between 2 and 3 mm in the coronal plane. Three-dimensional reconstructed images and virtual endoscopic images were generated with Advantage Windows by GE. RESULTS: Virtual endoscopic images could be generated in 20 patients with pancreatic cancer (76.9%). In these cases, we were able to observe the inner surface of the pancreatic duct and the stricture from not only the pancreatic head but also the pancreatic tail. Clear virtual images could not be generated in 6 cases. We were able to divide the 20 cases in which images could be generated into groups according to the appearance of the stricture. The edge of the stricture appeared to be protruding in 4 cases (15.4%), and appeared to be polygonal in 13 cases (50.0%). In 3 cases, we recognized the existence of a stricture, but the detail of the stricture was unclear. CONCLUSIONS: Virtual endoscopy caused minimal discomfort compared to real endoscopic examination, and it can access cystic lesions and the pancreatic duct behind the stricture. It is concluded that virtual endoscopy for pancreatic cancer has potential clinical utility.     

Multiple endocrine neoplasia type 1 presented with manic-depressive disorder: a case report with an identified MEN1 gene mutation

We report a case of multiple endocrine neoplasia type 1 who had repeated hypoglycemic episodes and had previously been diagnosed with bipolar manic-depressive disorder. The patient had a positive family history of multiple endocrine neoplasia type 1 and had multiple pancreatic endocrine tumors, hyperparathyroidism and possibly a pituitary tumor. The pancreatic tumors were resected by subtotal pancreatectomy and examined by histochemical staining and gene analysis. The tumor cells were positive for immunoreactive insulin and glucagon. A microsatellite polymorphism analysis revealed loss of heterozygosity on 11q13 in the tumors. By polymerase chain reaction-based nucleotide sequencing, we identified a germline mutation 483del2 of the MEN1 gene in the normal pancreatic tissue of the patient. This mutation causes a shift of the reading frame of menin mRNA at codon 125. It seems that the wild type allele of the MEN1 gene had been lost in the tumor cells whereas the mutant allele remained intact. This is the first identified MEN1 gene mutation in Japanese families and is different from all MEN1 gene mutations reported previously.