Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

Clinical Significance of Soluble Intercellular Adhesion Molecule-1 and Interleukin-6 in Patients with Extrahepatic Cholangiocarcinoma

ABSTRACT

Purpose/Aim: Although several prognostic factors for extrahepatic cholangiocarcinoma (EHC) have been reported, preoperative prognostic factors have yet to be established. We investigated the serum concentration of angiogenic, inflammatory, and nutritional parameters. Materials and Methods: Twenty-five patients with EHC were enrolled before starting treatment. Preoperative prognostic factors were identified using multivariate analyses. Results: The serum soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in the patients with EHC (436.0 ± 43.2 ng/ml) than in the healthy volunteers (228.6 ± 22.0 ng/ml) (p <.001). In addition, the serum IL-6 levels were significantly higher in the patients (18.0 ± 5.6 pg/ml) than in the healthy volunteers (5.7 ± 0.8 pg/ml) (p <.05). The serum IL-6 and sICAM-1 showed a strong correlation (r = 0.559) in the patients with EHC (p <.01). The serum IL-6 (area under the curve = 0.764, p =.030, cut-off level = 11.6) and sICAM-1 (area under the curve = 0.818, p =.007, cutoff level = 322.6) were revealed to be useful as prognostic factors by the receiver operating characteristic curves. The high IL-6 group and the high sICAM-1 group showed poorer DSS than those of the respective low groups. In the multivariate analysis, IL-6 (hazard ratio: 1.050, 95% confidence interval: 1.002–1.100, p =.043) and sICAM-1 (hazard ratio: 1.009, 95% confidence interval: 1.002–1.015, p =.009) were independent prognostic factors for DSS. Conclusions: IL-6 and sICAM-1 were independent preoperative prognostic factors in EHC patients, causing continuous inflammation and malnutrition in collaboration with other pro-angiogenic factors.     

Radiation-induced arteritis: thickened wall with prominent enhancement on cranial MR images report of five cases and comparison with 18 cases of Moyamoya disease

PURPOSE: To evaluate magnetic resonance (MR) imaging findings of radiation-induced cranial arteritis regarding arterial wall thickening and degree of enhancement, as well as to compare the findings with those of idiopathic moyamoya disease. MATERIALS AND METHODS: We reviewed cerebral MR images in five patients with radiation-induced large cerebral arteritis. All patients had undergone irradiation 2-25 years prior to this study. Conventional nonenhanced MR, MR angiographic, and contrast material-enhanced MR images were evaluated. Special attention was paid to wall enhancement of the affected arteries (distal internal carotid artery). Wall enhancement was staged in three levels by two neuroradiologists. We also reviewed MR images in 18 patients with primary moyamoya disease for comparison and analyzed them statistically (Fisher exact test). RESULTS: Wall thickening and prominent ring enhancement of the wall of the affected large cerebral arteries were observed in all (five of five) patients with radiation-induced arteritis. In contrast, wall thickening and prominent ring enhancement of the wall of the occluded arteries either were not seen (13 of 18 patients) or were faint (five of 18 patients) in patients with moyamoya disease. Contrast enhancement of the arterial walls in patients with radiation-induced arteritis was significantly more prominent than in patients with moyamoya disease (P =.003). CONCLUSION: MR images of wall thickening and prominent ring enhancement of the wall of affected large cerebral arteries may be a diagnostic clue in differentiating radiation-induced arteritis from moyamoya disease.     

MR-guided intravascular catheter manipulation: feasibility of both active and passive tracking in experimental study and initial clinical applications

PURPOSE: To evaluate clinically the feasibility and usefulness of MR-guided intravascular procedures with either active or passive tracking. METHODS: With an active MR tacking system and a 0.2 Tesla open MR imager, real-time and biplane displays of positions of a receive-only coil at the tip of catheters were obtained. For passive tracking, 4 Fr catheters with suitable susceptibility for passive tracking were used. Passive tracking with a 1.5 Tesla MR imager could be performed with parameters of TR 15-50 msec, TE 2.2-2.7 msec, and FA 30 degrees. The temperature of each tracking catheter was monitored in vitro. Clinical trials were performed on six patients (three each). The catheter was introduced to the superior mesenteric artery (SMA) under MR guidance by active or passive tracking to perform MR imaging during arterial portography. RESULTS: The temperature increased minimally. In humans, the SMA and celiac artery could be easily introduced on active tracking. MR-guided manipulation of catheters by active or passive tracking in the model and in dogs' vessels was very successful. Introduction of the catheter into the SMA was successful in two cases of active tracking and in all cases of passive tracking. CONCLUSION: The MR-guided intravascular manipulation of catheters by active or passive tracking may be a clinically feasible method.     

T1-weighted fluid-attenuated inversion recovery at low field strength: a viable alternative for T1-weighted intracranial imaging

BACKGROUND AND PURPOSE: T1-weighted spin-echo imaging has been widely used to study anatomic detail and abnormalities of the brain; however, the image contrast of this technique is often poor, especially at low field strengths. We tested a new pulse sequence, T1-weighted fluid-attenuated inversion recovery (FLAIR), which provides good contrast between lesions, surrounding edematous tissue, and normal parenchyma at low field strengths and at acquisition times comparable to those of T1-weighted spin-echo imaging. METHODS: Thirteen patients with brain lesions underwent T1-weighted spin-echo and T1-weighted FLAIR imaging during the same imaging session. T1-weighted spin-echo and T1-weighted FLAIR images were compared on the basis of four quantitative (lesion-white matter [WM] contrast-to-noise ratio [CNR], lesion-CSF CNR, gray matter-WM CNR, and WM-CSF CNR) and three qualitative criteria (conspicuousness of lesions, image artifacts, and overall image contrast). RESULTS: CNRs obtained with T1-weighted FLAIR were comparable but statistically superior to those obtained with T1-weighted spin-echo imaging. In general, T1-weighted FLAIR and T1-weighted spin-echo imaging produced comparable image artifacts. Conspicuousness of lesions and the overall image contrast were judged to be superior on T1-weighted FLAIR images. CONCLUSION: T1-weighted FLAIR imaging may be a valuable alternative to conventional T1-weighted imaging, because the former technique offers superior image contrast at low field strengths and comparable acquisition times.     

Evaluation of intracellular trafficking and clearance from HeLa cells of doxorubicin-bound block copolymers

New technologies are needed to deliver medicines safely and effectively. Polymeric nanoparticulate carriers are one such technology under investigation. We examined the intracellular trafficking of doxorubicin-bound block copolymers quantitatively and by imaging doxorubicin-derived fluorescence using confocal microscopy. The polymers were internalized by endocytosis and distributed in endosomal/lysosomal compartments and the endoplasmic reticulum; unlike free doxorubicin, the polymers were not found in the nucleus. Moreover, the ATP-binding cassette protein B1 (ABCB1) transporter may be involved in the efflux of the polymer from cells. This drug delivery system is attractive because the endogenous transport system is used for the uptake and delivery of the artificial drug carrier to the target as well as for its efflux from cells to medium. Our results show that a drug delivery system strategy targeting this endogenous transport pathway may be useful for affecting specific molecular targets.     

Mucinous cystadenoma of the pancreas with huge mural hematoma

A 60-year-old woman was referred for evaluation of a cystic mass in the pancreatic body that extended to the tail. Transabdominal ultrasonography demonstrated an oval cystic mass 24 cm in diameter, filled with debris. On the cyst wall there was a wide-based, smooth-surfaced, heterogeneous high-echoic protrusion that was 5 cm in diameter. On CT the protrusion showed internal enhancement. Endoscopic pancreatography showed no intraductal mucin or communication with the cyst. A distal pancreatectomy was performed under the diagnosis of mucinous cystadenocarcinoma. Grossly there was a brownish, hemispherical protrusion into the thin monolocular cyst. The cut surface of the protrusion showed a peripheral yellow-brownish area and an internal wine-colored area. Histopathologically the cyst wall consisted of tall columnar cells without atypical nuclei, ovarian-type stroma beneath the epithelium, and fibrotic tissue with abundant capillary vessels, suggestive of a mucinous cystadenoma. The protrusion was composed of peripheral organized hematoma without a covering epithelium, and internal hemorrhage and many capillary vessels, with no evidence of tumor cell necrosis. These histopathological findings appear to be similar to those of chronic expanding hematoma. The formation of a huge mural hematoma in a mucinous cystic neoplasm can occur as a repair process after the breaking of intrawall vessels.     

The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity

Adrenomedullin (AM) is a peptide involved both in the pathogenesis of cardiovascular diseases and in circulatory homeostasis. The high-affinity AM receptor is composed of receptor activity-modifying protein 2 or 3 (RAMP2 or -3) and the GPCR calcitonin receptor-like receptor. Testing our hypothesis that RAMP2 is a key determinant of the effects of AM on the vasculature, we generated and analyzed mice lacking RAMP2. Similar to AM-/- embryos, RAMP2-/- embryos died in utero at midgestation due to vascular fragility that led to severe edema and hemorrhage. Vascular ECs in RAMP2-/- embryos were severely deformed and detached from the basement membrane. In addition, the abnormally thin arterial walls of these mice had a severe disruption of their typically multilayer structure. Expression of tight junction, adherence junction, and basement membrane molecules by ECs was diminished in RAMP2-/- embryos, leading to paracellular leakage and likely contributing to the severe edema observed. In adult RAMP2+/- mice, reduced RAMP2 expression led to vascular hyperpermeability and impaired neovascularization. Conversely, ECs overexpressing RAMP2 had enhanced capillary formation, firmer tight junctions, and reduced vascular permeability. Our findings in human cells and in mice demonstrate that RAMP2 is a key determinant of the effects of AM on the vasculature and is essential for angiogenesis and vascular integrity.