Overexpression of cyclin‐dependent kinase 4 protein in extramammary Paget's disease

Cyclin‐dependent kinase 4 and 6 (CDK4/6) plays an important role in cell cycle progression, and the CDK4/6–cyclin D1 complex controls the cell cycle transition from G₁ phase to S phase. CDK4 is enhanced in several types of cancers and CDK4/6 inhibitors attenuate the proliferation of several types of cancer in vitro/in vivo. The purpose of our study was to investigate the expression pattern of CDK4 and evaluate its clinical importance in extramammary Paget's disease (EMPD). Almost all EMPD tissues were positive for CDK4, and metastatic lesions had a similar immunostaining intensity to primary lesions. In addition, CDK4 protein levels were positively correlated with those of cyclin D1 protein. Taken together, CDK4 may assume a crucial role in EMPD progression.     

Impact of venous invasion on the efficacy of adjuvant chemotherapy in elderly patients with stage III colorectal cancer

One of the reasons for the underuse of adjuvant chemotherapy in elderly patients with stage III colorectal cancer is a small survival benefit. This retrospective study sought to identify the predictive factors for elderly patients who could obtain a sufficient survival benefit. We reviewed the data of 1354 elderly patients (aged ≥70 years) with stage III colorectal cancer who underwent complete resection between January 1997 and December 2006. The efficacy of adjuvant chemotherapy was assessed, and the risk factors for recurrence were determined. The efficacy of adjuvant chemotherapy was also assessed after stratification for the above-mentioned risk factors for recurrence. There was a tendency for adjuvant chemotherapy to be effective in elderly patients (hazard ratio 0.84; 95% CI 0.70–1.01). Age, tumor location, pathology findings, tumor depth, venous invasion and lymph node metastasis were identified to be independent risk factors for recurrence by univariate and multivariate analyses. Among these factors, adjuvant chemotherapy was much effective in the elderly patients with high venous invasion (v2-3) (hazard ratio 0.69; 95% CI 0.52–0.91). High venous invasion (v2-3) was identified to be a predictive factor for elderly patients with stage III colorectal cancer who gained a sufficient survival benefit.     

Hyperthyroidism and the management of atrial fibrillation.

Atrial fibrillation is often induced in patients with hyperthyroidism and may trigger heart failure. Its prevalence and outcome were examined to obtain up-to-date information. Persistent atrial fibrillation was observed in approximately 1.7% of new hyperthyroid patients. It occurs more frequently in males (2.86%) than in females (1.36%), even though the number of male hyperthyroid patients is only one fifth of female patients. The rate increased with age, being 8% in the patients older than 70 years old. The initial treatment is to control the heart rate with routine pharmacologic therapy and to start antithyroid therapy as quickly as possible. Attempted cardioversion should be deferred until approximately the fourth month of maintaining a euthyroid state, because more than 56% of atrial fibrillation spontaneously reverts to sinus rhythm when the thyroid hormone levels start to decline. Elective cardioversion for those whose atrial fibrillation persists is highly effective and sinus rhythm maintenance rates were 56.7% and 47.6% at the 10th and the 14th year, respectively, even though the duration of atrial fibrillation prior to cardioversion was extremely long (35.0 +/- 29.0 months).     

Cancer and non-cancer excess mortality resulting from mixed exposure to polychlorinated biphenyls and polychlorinated dibenzofurans from contaminated rice oil: “<Emphasis Type="Italic">Yusho</Emphasis>”

Purpose

In 1968, rice oil contaminated with polychlorinated biphenyls and polychlorinated dibenzofurans caused a severe outbreak of food poisoning in Japan and was termed locally as “Yusho” (oil disease). In our previous study, we found that area-based standardized mortality ratios (SMRs) of some diseases were elevated shortly after the incident. This previous study, however, was unable to determine whether these elevated SMRs were a result of other area-specific factors. To overcome this limitation, we obtained mortality data from the 5 years before the incident and conducted an area-based study using vital statistics records dating from 1963 to 2002.

Methods

The population of Nagasaki Prefecture was set as the reference population for calculating SMRs. We also included data on cause-specific mortality attributable to cancer and expanded the population to encompass two severely exposed areas where contaminated rice oil was distributed (namely Tamanoura and Naru). We also calculated SMRs in the remainder of the Shimo-Goto region, excluding the exposed area, which was used as a comparison area.

Results

Even after considering the time trends in mortality before the incident, mortality due to diabetes mellitus and heart disease, as well as all-cause mortality, was found to be elevated shortly afterward. Additionally, mortalities due to uterine cancer in Tamanoura and leukemia were also elevated at 30–34 and 10–59 years after the event in both exposed areas, respectively. SMRs for leukemia in Tamanoura were as high as 3.0 (95 % confidence interval 1.4–6.2) and 2.4 (1.2–4.8) 10–19 years later. In this period, SMRs for leukemia in the comparison area were not elevated.

Conclusions

Further epidemiological studies are needed regarding this rice-oil, “Yusho” outbreak, especially with regard to cancer and non-cancer mortality.

     

Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice

An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10–50?mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72?hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60?min was recorded and summed. We found that at 24?hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.     

Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys

Contrast‐induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty‐six patients were enrolled (32 men; mean age, 75.3 ± 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1.73 m² (CKD and non‐CKD groups, n = 18 in both). Average peak velocity (APV) and renal artery resistance index (RI) were measured by Doppler flow wire before and after administration of the iodinated contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = ?0.627, P < 0.001). Mean RI was significantly higher (P = 0.015) and APV was significantly lower (P = 0.026) in the CKD than in the non‐CKD group. Both APV (P < 0.001) and RI (P = 0.002) were significantly changed following contrast media administration in the non‐CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media.