Pelvic insufficiency fracture after definitive radiotherapy for uterine cervical cancer: retrospective analysis of risk factors

The purpose of this study is to determine the incidence, clinical characteristics and risk factors of postradiation pelvic insufficiency fracture (PIF) in women with uterine cervical cancer. We reviewed the medical records of 126 patients who received definitive radiotherapy (RT) for uterine cervical cancer between 2003 and 2009 at our institution. Among them, 99 patients who underwent at least one computed tomography (CT) or magnetic resonance imaging of the pelvis during their follow-up at more than 6 months were included in this analysis. The relationship between the incidence of PIF and several patient- and treatment-related factors was analyzed. The median follow-up period was 21 months. Of the 126 patients, 33 (with a total of 50 lesions) were diagnosed with PIF. The 2-year cumulative incidence was 32%. Univariate analysis showed that age ≥70 years (P= 0.0010), postmenopausal state (P = 0.0013), and lower CT density of bone and bone marrow (P= 0.020) significantly related to PIF. In a multivariate analysis, of the 59 patients whose CT densities were evaluable, lower CT density was the only significant factor associated with PIF (P = 0.0026). In conclusion, postradiation PIFs were detected in a considerable number of patients after definitive RT for cervical cancer. Predisposing factors were older age, postmenopausal state, and decreased density of bone and bone marrow on CT.     

Heredity mode of genetic polymorphism in aldehyde oxidase activity in Donryu strain rats

Donryu strain rats show genetic polymorphisms in the aldehyde oxidase gene, resulting in the phenotypic expression of ultrarapid metabolizers with homozygous nucleotide sequences (337G, 2604C), extensive metabolizers with heterozygous nucleotide sequences (377G/A, 2604C/T), and poor metabolizers with homozygous nucleotide sequences (377A, 2604T). In the mating experiments the ratio of the number of ultrarapid metabolizers, extensive metabolizers, and poor metabolizers rats in the F1 generation from the heterozygous F0 extensive metabolizers male and female rats was roughly 0.6 : 1.5 : 1, and the ratio converged to approximately 1 : 2 : 1 in the F2 generation from the heterozygous F1 extensive metabolizers male and female rats. On the contrary, all the F2 generation from homozygous F1 ultrarapid metabolizers male and female rats or from homozygous F1 poor metabolizers male and female rats had the ultrarapid metabolizers or the poor metabolizers genotypes and phenotypes. The genotypes completely agreed with the phenotypes in all individuals of F0, F1, and F2 generations. The results indicate that the genetic polymorphism of aldehyde oxidase in Donryu strain rats obeys Mendelian heredity. The reason for a low ratio of the ultrarapid metabolizers rats in the commercially available Donryu strain rats?—?not more than several per cent?—?compared with the ratio expected from the Mendelian rule is unknown.     

Leukotriene B4 12-hydroxydehydrogenase/15-ketoprostaglandinΔ13-reductase (LTB4 12-HD/PGR) responsible for the reduction of a double-bond of the α,β-unsaturated ketone of an aryl propionic acid non-steroidal anti-inflammatory agent CS-670

CS-670 is a non-steroidal anti-inflammatory agent with an α,β-unsaturated ketone structure. It exerts its pharmacological activity after being transformed to the active metabolite (2S,1′R,2′S)-trans-alcohol. Two consecutive reductions are needed for the formation of the active metabolite, reduction of the double-bond of the α,β-unsaturated ketone moiety, followed by reduction of the resulting saturated ketone. The objective of the current study was to identify the enzyme responsible for reduction of the double-bond. An enzyme purified from rat liver cytosol as a single band on sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was analysed by a Mascot database search of nano-LC tandem mass spectrometry (MS/MS) data and the enzyme was identified as 2-alkenal reductase (EC 1.3.1.74), which is known as an β-nicotinamide adenine dinucleotide phosphate (NADPH)-dependent alkenal/one oxidoreductase and has a role for leukotriene B₄ 12-hydroxydehydrogenase/15-ketoprostaglandinΔ13-reductase (LTB₄ 12-HD/PGR). The identification was confirmed by cloning LTB₄ 12-HD/PGR cDNA from rat liver, expressing it in Escherichia coli, and characterizing the properties of the enzyme. The identity was further supported by the subcellular localization in cytosol, a cofactor requirement for NADPH, substrate specificity, and substantial inhibition by 15-ketoPGF_2α, benzylideneacetophenone, indomethacin, and quercitrin. In addition to catalysing the biological reduction of eicosanoids, including prostaglandins, leukotrienes, and lipoxins, LTB₄ 12-HD/PGR was also determined to function as a xenobiotic-metabolizing enzyme.     

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients

Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.     

Development of port-site metastasis after pneumoperitoneum

Background: Port-site metastasis is a critical problem in laparoscopic cancer surgery; the pathogenesis and means of prevention are still unclear. The aim of this study was to clarify by scanning electron microscopy the initial morphologic changes in the development of port-site metastasis. Methods: Fifteen nude mice were injected with human gastric cancer (MKN 45) cells. Mice were killed on days 0, 3, and 8 (n = 5 each day) after intraperitoneal injection of 5 × 105 cancer cells and carbon dioxide (CO2) pneumoperitoneum at 4–6 mmHg for 20 min. The abdominal wall with the port sites was harvested and examined under both light and scanning electron microscopy. Results: Immediately after CO2 pneumoperitoneum (day 0), the abdominal peritoneum was peeled away and the muscular layer was destroyed at the port site in all mice. Several cancer cells were attached to the injured port sites. On day 3, the subperitoneal tissue and muscular layer defects were replaced by granulation tissue, and several cancer cells were observed in the subperitoneal tissue. On day 8, a small nodule was macroscopically visible at the port site; it was completely covered by mesothelial cells and consisted of numerous cancer cells. Conclusions: Free cancer cells appear to attach to the injured port sites immediately after CO2 pneumoperitoneum, and these are associated with the development of port-site metastasis after laparoscopic cancer surgery.     

Laparoscopic rectal surgery for middle and lower rectal cancer

Background  

The usefulness of laparoscopic low anterior resection for middle and lower rectal cancer remains controversial.     

Long-term survival and functional recovery after isolated coronary artery bypass grafting in patients with severe left ventricular dysfunction

Objective  Coronary artery bypass grafting (CABG) in patients with left ventricular dysfunction has been considered to be a challenging operation. We assessed the early angiographic and long-term clinical and functional outcomes of patients with poor left ventricular function who underwent isolated CABG. Methods  We retrospectively reviewed the records of 78 patients with a poor left ventricular ejection fraction (35% or less) who underwent isolated CABG between January 1991 and November 2006. The mean age of the patients was 66.1 ± 9.4 years, and their mean New York Heart Association functional class was 3.1 ± 0.8. Their mean end-diastolic left ventricular diameter was 57.4 ± 8.1 mm, and their mean grade of mitral regurgitation was 0.7 ± 1.0. Early postoperative angiograms were performed at 32.5 ± 33.5 days after the operation. Interval echocardiographic data were analyzed, and the long-term survival rate was evaluated. Results  The average number of distal anastomoses per patient was 3.2 ± 1.1. The operative mortality rate was 7.7%. Stroke occurred in 1.3% of patients. The overall patency rates for arterial and venous grafts were 100% and 97.2%, respectively. The left ventricular ejection fraction significantly improved from 28.2% ± 5.1% to 34.4% ± 8.4%. Both the end-diastolic and end-systolic left ventricular dimensions significantly decreased from 57.4 ± 8.1 to 55.1 ± 8.8 mm and from 47.4 ± 8.4 to 45.1 ± 9.7 mm, respectively. The actuarial patient survival rate at 10 years was 73.1%. Conclusion  CABG in patients with left ventricular dysfunction was effective, with favorable early graft patency rates. The long-term outcome was also acceptable, with echocardiographic functional recovery.     

Type B aortic dissection associated with <Emphasis Type="Italic">Salmonella</Emphasis> infection

A 59-year-old man with a long history of hypertension and diabetes was admitted to our hospital with acute type B aortic dissection 14 days after the sudden onset of back pain. The dissecting descending thoracic aorta was enlarged to 5.2 cm in diameter, and laboratory tests showed an elevated white blood cell count (15 530/mm³) and an increased C-reactive protein level (19.2 mg/dl). Computed tomography performed 2 days after admission revealed rapid growth of the aortic dissection. Blood cultures obtained upon admission were positive for Salmonella. Impending rupture of the aortic dissection complicated by Salmonella infection was strongly suspected, and the patient underwent emergency surgery consisting of debridement and prosthetic graft placement covered by an omental flap. In this case, it is believed that insidious Salmonella aortitis caused acute type B aortic dissection.     

Could a policy of provision of hip protectors to elderly nursing home residents result in cost savings in acute hip fracture care? The case of Ontario, Canada

Summary Hip fractures are an important problem in nursing homes. Hip protectors are external devices that decrease the risk of hip fracture in elderly nursing home residents. We estimated the overall healthcare cost savings from a hypothetical strategy of provision of hip protectors to elderly nursing home residents in Ontario, Canada. In a recent meta-analysis, we determined that a strategy of provision of hip protectors decreases the risk of hip fracture in nursing home residents. Introduction Our objective was to determine whether the provision of hip protectors to all Ontario nursing home residents aged ≥65 years could result in cost savings, stemming from reductions in initial hospitalizations for hip fracture. Methods We conducted a cost analysis from a Ministry of Health perspective (one year cycle length). The efficacy of the intervention was estimated from a meta-analysis of randomized controlled trials. Results A strategy of provision of hip protectors to all 60,775 elderly Ontario nursing home residents could result in an overall mean cost savings of 6.0 million Canadian dollars in one year (95% credibility interval, −26.4 million, 39.7 million), with a probability of cost savings of 0.63 (assuming no additional labor costs). In sensitivity analyses, decreasing hip protector price increased cost savings, whereas additional labor expenditures for application for hip protectors decreased cost savings. Conclusion In conclusion, if hip protectors can be provided to elderly Ontario nursing home residents without additional labor expenditures, there is a reasonable probability that such a strategy may result in healthcare cost savings.