Progress in multidisciplinary treatment for esophageal cancer in Japan as reflected in JCOG studies

Changes in the standard treatment for esophageal cancer in Japan are reflected in the history of consecutive studies conducted by the Japan Esophageal Oncology Group (JEOG), a subgroup of the Japan Clinical Oncology Group (JCOG). Following the era of preoperative radiotherapy in the 1970s, the emphasis in surgical adjuvant therapy shifted from postoperative radiotherapy in the 1980s to postoperative chemotherapy including cisplatin as a key drug in the 1990s. Later, the optimal timing for perioperative adjuvant therapy returned to before surgery based on the results of a JCOG study (JCOG9907) that compared preoperative chemotherapy with postoperative chemotherapy in the late 2000s. Next, the clinical question of which is better, preoperative aggressive chemotherapy or preoperative chemoradiotherapy, still needs to be resolved. Concurrent chemoradiotherapy using cisplatin and 5-fluorouracil became a standard non-surgical treatment for esophageal cancer from the early 1990s onwards. Based on the preferable results of definitive chemoradiotherapy for unresectable advanced disease, definitive chemoradiotherapy was considered to be a possible alternative treatment modality in stage I esophageal cancer patients. Therefore, JEOG conducted a phase III study (JCOG0502) to demonstrate the non-inferiority of chemoradiotherapy compared with surgery in patients with stage I esophageal squamous cell carcinoma. If definitive chemoradiotherapy fails in patients with stage II/III esophageal cancer, salvage surgery is now recommended. Therefore, JEOG has initiated a phase II study (JCOG0909) to evaluate the efficacy and safety of this combined treatment modality.     

APOE and CYP2E1 polymorphisms, alcohol consumption, and Parkinson's disease in a Japanese population

Apolipoprotein E (APOE) is associated with increased oxidative stress, which is caused by reactive oxygen species (ROS). Enhanced cytochrome P450 2E1 (CYP2E1) activity may also increase formation of neurotoxins such as ROS. As Parkinson??s disease (PD) is a neurodegenerative disorder, both the APOE and CYP2E1 genes that are involved in neurodegeneration by oxidative stress may be associated with PD risk. We investigated the relationship of the APOE and CYP2E1 rs2864987 polymorphisms and PD risk with special attention to the interaction with alcohol consumption among 238 patients with PD and 296 controls in a Japanese population. The frequencies of the ?2, ?3, and ?4 alleles of the APOE polymorphism among controls were 3.72, 86.7, and 9.63%, respectively. As compared with the APOE ??3/??3 genotype, the 2/??4 genotype was associated with an increased risk of PD (adjusted odds ratio (OR) = 9.50, 95% (confidence interval) CI = 1.12?C80.6). The presence of the ??3 allele was associated with a decreased risk of PD. Meanwhile, CYP2E1 rs2864987 was not associated with PD risk. Although CYP2E1 is involved in the metabolism of alcohol, there was no evidence of interaction between alcohol consumption and CYP2E1 rs2864987. Our results suggested that the APOE polymorphism might play an important role in PD susceptibility in our Japanese population. Future studies involving larger control and case populations and better alcohol consumption histories will undoubtedly lead to a more thorough understanding of the role of polymorphisms of genes related to the generation of ROS in PD development.     

Campylobacter jejuni DNA-binding protein from starved cells in Guillain–Barré syndrome patients

Campylobacter jejuni enteritis is frequently associated with an axonal form of Guillain–Barré syndrome (GBS) and C. jejuni DNA-binding protein from starved cells (C-Dps) induces paranodal myelin detachment and axonal degeneration through binding with sulfatide in vivo. Here we investigated the invasion of C-Dps into hosts with C. jejuni-related GBS. Our analyses of patient sera found that both C-Dps and anti-C-Dps antibodies were most commonly detected in sera from C. jejuni-related GBS patients (5/27, 14.8% and 15/24, 62.5%; respectively). These findings suggest that C-Dps invades the host and may potentially contribute to the peripheral nerve damage in C. jejuni-related GBS.     

Enhanced accumulation of phosphorylated alpha-synuclein in double transgenic mice expressing mutant beta-amyloid precursor protein and presenilin-1

A recent report showed that the accumulation of alpha-synuclein (alpha-syn) was detected in the brains of one-third of Alzheimer's disease and Down syndrome patients. However, the relationship between amyloid-beta protein (Abeta) and alpha-syn remains unclear. We analyzed the relation between the mutation of presenilin-1 (PS-1) and the pathological features of beta-amyloidosis and alpha-synucleinopathy. We generated doubly transgenic mice overexpressing mutant beta-amyloid precursor protein (betaAPP; Tg2576) and mutant PS-1 (PS1L286Vtg; line 198) and analyzed 19 double Tg betaAPP(+)/PS(+) mice at 5-23 months (young to old), 23 age-matched single Tg betaAPP(+)/PS(-) mice, and 11 non-Tg littermates. Immunohistochemical comparison was performed in these three groups by counting the area and the number of alpha-syn- or phosphorylated alpha-syn (palpha-syn)-positive dystrophic neurites per plaque (ASPDN, pASPDN). The acceleration of Abeta pathology was found with earlier onset and exaggerated numbers in double Tg betaAPP(+)/PS(+) compared with single Tg betaAPP(+)/PS(-) mouse brains. The accumulation of ASPDN and pASPDN was also accelerated in double Tg betaAPP(+)/PS(+) compared with single Tg betaAPP(+)/PS(-) mouse brains, especially in pASPDN. The number and area of alpha-syn and palpha-syn, and the ratio of palpha-syn positive neurites were significantly higher in double Tg betaAPP(+)/PS(+) than in single Tg betaAPP(+)/PS(-) mouse brains in middle-aged and old groups. Additional overexpression of mutant PS-1 accelerated Abeta-induced alpha-synucleinopathy and further facilitated the phosphorylation of alpha-syn, suggesting a direct association between mutant PS-1 and phosphorylation of alpha-syn.     

Health-related quality of life in patients undergoing lithotripsy for urinary stones

Objectives The objective of this study was to analyze the health-related quality of life (HRQoL) in patients undergoing lithotripsy for urinary stones. Materials and methods This study comprised 76 patients with urinary stones who were treated by lithotripsy, which included shock wave lithotripsy (SWL), ureteroscopic lithotripsy, percutaneous nephrolithotripsy and ureterolithotomy in 66 patients, 25 patients, six patients and three patients, respectively. During the observation period of this series, 37 patients received additional lithotripsy for recurrent urinary stones. HRQoL was evaluated using the Short Form-36 (SF-36) survey assessing eight aspects associated with general health status. Results There were no significant differences in any scale scores between the 76 patients with urinary stones and age- and gender-matched Japanese norms. Bodily pain (BP) in 37 patients undergoing lithotripsy twice or more appeared to be significantly lower than that in 39 undergoing lithotripsy only once; however, there were no significant differences in the remaining seven scores according to the number of courses of lithotripsy. Furthermore, 47 patients treated by SWL alone had a significantly higher score for general health perception (GH) than 29 who underwent lithotripsy by methods other than SWL, while there were no significant differences in the remaining seven scores between these two groups. Conclusions In general, patients undergoing lithotripsy for urinary stones may have a comparatively favorable HRQoL; however, BP and GH were impaired in patients undergoing lithotripsy twice or more and those treated by invasive modalities, respectively. Considering these findings, it would be important to prevent recurrent stone formation and to develop less invasive procedures to further improve HRQoL in patients undergoing lithotripsy for urinary stones.     

Glenohumeral joint motion after medial shift of the attachment site of the supraspinatus tendon: a cadaveric study

During a rotator cuff repair, it is ideal to reattach the torn edge of the cuff tendon back to the greater tuberosity. However, with massive tears where the torn edges are too retracted to be reattached to the greater tuberosity, they may have to be reattached somewhere more medial. It is clinically important to know how far medially one can shift the reattachment site without sacrificing function of the shoulder. Ten fresh, previously-frozen cadaveric shoulders were used. Medial shift of the supraspinatus tendon was simulated by placing the suture anchors along lines 3, 10, or 17 mm medial to the cuff attachment site. The ranges of glenohumeral motion were measured using a goniometer with a constant torque applied to the humerus. All motions, except for internal rotation at 60 degrees of abduction, were significantly restricted by medial shift of 10 mm or more compared with that of the intact shoulder. We conclude that significant restriction of joint motion occurs when a bony trough is created more than 10 mm medial to the cuff attachment site.     

A comparison of clinical features between chlamydial and non-chlamydial urethritis in men negative for gonococcal infection who attended a urological outpatient clinic in Japan

Objectives The objective of this study was to investigate the clinical features of non-gonococcal urethritis in men who attended a urological outpatient clinic in Japan. Materials and methods This study included a total of 194 patients diagnosed as having non-gonococcal urethritis and subsequently judged as cured following antibiotic therapy between January 2001 and June 2005. Clinical data were analyzed after dividing these patients into two groups as follows: 96 patients with chlamydial urethritis (CU) and 98 with non-chlamydial urethritis (NCU). Results The incubation period in the CU group was significantly longer than that in the NCU group (P = 0.0020). The incidence of severity of symptoms in the NCU group was significantly greater than that in the CU group (P = 0.022), and the interval between the appearance of the initial symptom and consulting the clinic was significantly shorter in the NCU group than in the CU group (P = 0.0015). The proportion of commercial sex workers (CSWs) as the causative partner in the NCU group was significantly greater that in the CU group (P < 0.001), and the incidence of oral sex as the causative mode of sexual interaction was significantly more frequent in the NCU group than that in the CU group (P = 0.021). The duration of antibiotic therapy until cured was significantly longer in the CU group than in the NCU group (P = 0.0051). Furthermore, multivariate analysis showed that whether the infection involved CU or NCU was independently associated with the treatment interval irrespective of other factors examined (P = 0.041). Conclusions These findings suggest that the clinical characteristics of CU and NCU clearly differ and that CU tends to require a longer time to cure than NCU; therefore, among patients with non-gonococcal urethritis, it would be particularly important to effectively control the spread of CU.