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.     

Dynamic Changes with Liver Atrophy as an Alternate Marker of Chemotherapy-Associated Liver Injury

Annals of Surgical Oncology -     

Five percent, 7.5% or 10% hypertonic saline prevents delayed neuronal death in gerbils

PURPOSE: To clarify the appropriate concentration and dose of hypertonic saline solution (HSS) for preventing delayed neuronal death in the hippocampal CA1 subfield after transient forebrain ischemia in gerbils. METHODS: Thirty gerbils were randomly assigned to five groups: physiological saline solution (PSS) group, ischemia/reperfusion treated with PSS 2 mL x kg(-1); 5% HSS group, treated with 5% HSS 2 mL x kg(-1); 7.5% HSS group, treated with 7.5% HSS 2 mL x kg(-1); 10% HSS group, treated with 10% HSS 2 mL x kg(-1); 20% HSS group, treated with 20% HSS 2 mL x kg(-1). Transient forebrain ischemia was induced by occluding the bilateral common carotid arteries for four minutes. Five days later, histopathological changes in the hippocampal area were examined, and the degenerative ratio of the pyramidal cells were measured according to the following formula: (number of degenerative pyramidal cells/total number of pyramidal cells per 1 mm of hippocampal CA1 subfield) x 100. RESULTS: In PSS and 20% groups, neuronal cell damage was observed five days after ischemia. In the other three groups, these changes were not observed. The degenerative ratios of pyramidal cells were as follows; PSS group: 91.6 +/- 5.6%, 5% HSS group: 7.2 +/- 1.6%, 7.5% group: 8.3 +/- 1.4%, 10% HSS group: 6.2 +/- 1.1%, 20% HSS group: 85.8 +/- 8.7% (P < 0.05; PSS and 20% HSS vs three other groups). CONCLUSION: This study demonstrates that 5, 7.5 or 10% HSS 2 mL x kg(-1) may prevent delayed neuronal death in the hippocampal CA1 subfield after cerebral ischemia/reperfusion in gerbils.     

Lobar intracerebral hemorrhage. A clinical, radiographic, and pathological study of 29 consecutive operated cases with negative angiography.

The authors operated consecutively on 50 patients with lobar intracerebral hemorrhage during a prospectively designed study period from January, 1986, to March, 1990. They investigated the correlations between the underlying causes and the clinicoradiographic features in 29 patients who showed no angiographic vascular abnormalities, in order to elucidate the operative indication for such cases. Patients with ruptured saccular aneurysm or trauma were not included in this study. There were 15 males and 14 females, ranging in age from 7 to 76 years (mean 52.4 years). Histological diagnoses of the surgical specimens were as follows: vascular malformation in nine cases (arteriovenous malformation (AVM) in six and cavernous malformation in three), microaneurysm in 11, cerebral amyloid angiopathy in six, and brain tumor in two; in the remaining case the cause was not verified histologically. The underlying cause was determined in 96.5% of cases. The mean patient age was lowest in the cavernous malformation group (27.0 years), followed by the AVM (45.8 years), microaneurysm (59.8 years), and cerebral amyloid angiopathy (70.0 years) groups. Four patients with vascular malformation (three AVM's and one cavernous malformation) had previous episodes of bleeding at the same site, whereas none of those with microaneurysms or cerebral amyloid angiopathy had such episodes. On computerized tomography (CT) scans, the round to oval hematoma was related to the presence of an AVM or cavernous malformation in contrast to microaneurysms and cerebral amyloid angiopathy. Upon infusion of contrast material, variable enhancement was seen in five (two AVM's and three cavernous malformations) of the nine vascular malformations while no enhancement was noted in any patient with microaneurysm or cerebral amyloid angiopathy at the acute stage. Subarachnoid extension of the hematoma was associated with cerebral amyloid angiopathy significantly more frequently than with AVM's (p less than 0.05) and microaneurysms (p less than 0.01). The results suggest that clinicoradiographic pictures in cases with negative angiography are quite different among the three major pathological categories; namely, vascular malformation (AVM and cavernous malformation), microaneurysm, and cerebral amyloid angiopathy. It is suggested that the underlying etiology of a given lobar intracerebral hemorrhage with negative angiography may be predicted by a combination of patient age, history of previous bleeding at the same site, hematoma shape, and subarachnoid extension of the hematoma on CT scans. Based upon these findings, the authors discuss operative indications for such cases.     

Granulocytic sarcoma presenting with lymph node infarction at disease onset

A completely infarcted lymph node is an unusual event. However, lymph node infarction should alert the pathologist to the considerable likelihood of malignant lymphoma. We report two unusual cases of acute myeloid leukemia presenting with granulocytic sarcoma at disease onset with a lymph node lesion exhibiting extensive lymph node infarction. The infarcted tissue contained numerous eosinophilic cell ghosts. There were some islands of degenerated, pyknotic medium-sized nuclei resembling lymphoblasts present in the necrotic area. By immunohistochemistry, these medium sized cells were CD3-, CD20-, CD34+, CD43+, CD45RO-, CD68-, CD79a- and myeloperoxidase+ in both cases. Differentiation of granulocytic sarcoma from malignant lymphomas is important for adequate therapy. The present cases indicate that granulocytic sarcoma should be added to the list of differential diagnoses for lymph node infarction.     

Primary pulmonary low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with prominent hyalinosis. A case report

We report a case of primary pulmonary low-grade marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type with prominent sclerosis, which morphologically resembled pulmonary hyalinizing granuloma (PHG) or inflammatory pseudotumor (IPT) of the lung. The patient, a 66-year-old Japanese female with a history of Sj?gren's syndrome and primary biliary cirrhosis, presented with a lower left lobe mass 6.8 cm in diameter. Histologically, the lesion is characterized by dense bundles of collagen with scattered plasma cells, mature small lymphocytes, and histiocytes among the collagen bundles. Only the peripheral area of the nodule contained dense lymphoplasmacytoid and histiocytoid infiltrates. A few centrocyte-like cells were obscured by the numerous plasma cells and plasmacytoid cells. In addition, lymphoepithelial lesions and colonalized lymphoid follicles were identified by immunohistochemistry alone. Although PHG and IPT are unlikely to be confused with pulmonary MALT-type lymphomas, the present case suggests that MALT-type lymphoma should be added to the list of differential diagnoses for PHG and IPT.     

Follicular hyperplasia presenting with a marginal zone pattern in a reactive lymph node lesion

Histologically, the marginal zone pattern of the lymph node is characterized by lymphoid follicles with three distinct layers. The inner layer is composed of follicular center zones, the middle layer of darkly stained mantle zones, and the outer layer of marginal zones. However, the marginal zone pattern is rarely seen in reactive lymph nodes except for mesenteric lymph nodes. We describe the clinicopathologic, immunohistochemical and genotypic findings of six cases of reactive follicular hyperplasia exhibiting the marginal zone pattern. The patients comprised three males and three females (age range 24 to 63 years; medium 56 years). Follow-up data were obtained from five patients. None of them developed malignant lymphomas during the follow-up period of from 5 to 204 months (median 68 months). Histologically, the lesion was characterized by numerous lymphoid follicles and partial distortion of lymph node structure. Varying degrees of progressive transformation of the germinal center (PTGC) were noted in the four cases. The marginal zone pattern was observed in some or most of the lymphoid follicles including PTGC. The marginal zone B cells were small to medium-sized lymphocytes with round or slightly indented nuclei and a broad rim of pale cytoplasm. Some of them had a monocytoid appearance. They were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD10-, CD21-, CD23-, CD43-, CD45RO-, Bcl-6-, cyclin D1-, EMA- and p53-. A portion of them were Bcl-2 positive. Occasional large lymphoid cells with round or indented nuclei and moderate amounts of cytoplasm were observed in the marginal zone in four cases. These large lymphoid cells were usually CD20 positive, but Bcl-6 negative. A small number of them contained polytypic intracytoplasmic immunoglobulins. The polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Recognition of unusual marginal zone hyperplasia in reactive lymph node lesions is important to avoid confusion with nodal involvement in various low-grade B cell lymphomas presenting a marginal zone distribution pattern.     

Analysis of intestinal HLA-DR bound peptides and dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease

Isolation of antigenic peptides from the MHC-groove has contributed to the understanding of T cell responses. However, these MHC-associated peptides have been isolated from various murine and human cell lines. The specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We examined antigenic peptides bound to the class II major histocompatibility complex (MHC) groove in human intestine by ion-trap tandem mass spectrometry equipped with online reverse-phase high performance liquid chromatography. We detected 55 parent proteins from 4 controls, 9 patients with ulcerative colitis, and 9 patients with Crohn's disease. The calculated molecular masses (m/z) of these peptides ranged from 874.4 to 2727.4, representing 10-26 amino acid residues. Fifty-one of these 55 parent proteins were exogenous proteins. Escherichia coli-, Saccharomyces cerevisiae-, and Caenorhabditis elegans-derived peptides were found frequently in patients with inflammatory bowel disease. The present results suggest that in vivo antigen processing by antigen-presenting cells and T lymphocytes in human intestine participate with exogenous antigen presentation. Increased immune responses against E. coli, S. cerevisiae and C. elegans found in patients with inflammatory bowel may participate as dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.     

A study on how a 6-month aerobic exercise program can modify coronary risk factors depending on their severity in middle-aged sedentary women

It is well known that physical exercise can reduce coronary risk factors. But how an aerobic exercise modifies coronary risk factors in relation to severity and physical fitness is still controversial. Fifty-four middle-aged women (mean age, 55 years) completed a 6-month on-site and home-based anaerobic threshold-level exercise program. The changes in coronary risk factor profiles were observed during the pre-intervention and intervention periods. Before the intervention (during control period), most coronary risk factors showed a rather unfavorable trend. After the program, their mean body weight decreased from 56.7 to 55.7 kg (p>0.05) and the proportion of body fat from 30.9 to 27.9% (p>0.05) without any reduction in lean body mass. Systolic blood pressure (SBP) decreased from 129.0 to 125.0 mm Hg (p>0.05) and diastolic blood pressure from 79.5 to 76.6 mm Hg (p>0.05). Fasting plasma glucose (FPG) declined from 109.6 to 103.4 mg/dl (p>0.05). Changes in SBP and FPG were most remarkable in their respective worst tertile. Serum lipids improved only modestly. Maximum oxygen uptake increased from 23.6 to 26.1 ml/kg/min (p>0.01). However, no significant correlations were found between changes in coronary risk factors and those in physical fitness. We conclude that the 6-month aerobic exercise program would modify women’s coronary risk factors depending on their initial values, probably independently of the changes in physical fitness.