Biochemical modulation therapy for pancreatic cancer

It is well known that the clinical course in most patients with advanced pancreatic cancer is not influenced substantially by chemotherapy and/or radiotherapy. However, new chemotherapy, based on the synergistic antitumor activities of 5-fluorouracil (5-FU) and cisplatin (CDDP) producing biochemical modulation in solid cancers diagnosed as adenocarcinoma, has recently been reported to be effective. In gastrointestinal cancers, the optimal concentrations of each drug and the duration of the anticancer effects, as well as adverse effects have been confirmed in pharmacodynamic studies. Our experience of this treatment for advanced pancreatic cancer (stage IV) indicates the usefulness of the antitumor effect in terms of both effect on the tumor size in unresectable patients and prognosis in resectable patients. These results were remarkable in patients diagnosed as stage IV b and/or curability C. Although there were adverse effects, none were severe. However, anything compromising the patient's quality of life must be prevented. Randomized prospective studies of the combination of 5-FU and CDDP are expected in the near future. Received for publication on July 29, 1998; accepted on July 31, 1998     

Association between serum uric acid and new onset and progression of chronic kidney disease in a Japanese general population: Iki epidemiological study of atherosclerosis and chronic kidney disease

Clinical and Experimental Nephrology - Although several risk factors for chronic kidney disease (CKD) have been proposed, it remains unclear whether elevated serum uric acid (SUA) is negatively...     

Isolation and molecular analysis of circulating tumor cells from lung cancer patients using a microfluidic chip type cell sorter

Circulating tumor cells (CTCs) are a tumor‐derived material utilized for liquid‐based biopsy; however, capturing rare CTCs for further molecular analysis remains technically challenging, especially in non‐small‐cell lung cancer. Here, we report the results of a clinical evaluation of On‐chip Sort, a disposable microfluidic chip‐based cell sorter, for capture and molecular analysis of CTCs from patients with lung adenocarcinoma. Peripheral blood was collected from 30 metastatic lung adenocarcinoma patients to enumerate CTCs using both On‐chip Sort and CellSearch in a blind manner. Captured cells by On‐chip Sort were subjected to further molecular analysis. Peripheral blood samples were also used for detection of EGFR mutations in plasma using droplet digital PCR. Significantly more CTCs were detected by On‐chip Sort (22/30; median 5; range, 0–18 cells/5 mL blood) than by CellSearch (9/30; median, 0; range, 0–12 cells/7.5 mL) (P < 0.01). Thirteen of 30 patients who had a negative CTC count by CellSearch had a positive CTC count by On‐chip Sort. EGFR mutations in CTCs captured by On‐chip Sort were observed in 40.0% (8/20) of patients with EGFR‐mutated primary tumor. EGFR mutations were often observed in 53.3% (8/15) of patients detected in plasma DNA. Expressions of EGFR and vimentin protein on CTCs were also successfully assessed using On‐chip Sort. These results suggest that On‐chip Sort is an efficient method to detect and capture rare CTCs from patients with lung adenocarcinoma that are undetectable with CellSearch. Mutation detection using isolated CTCs remains to be further tackled (UMIN000012488).     

Brain ischemia and gastric mucosal damage in spontaneously hypertensive rats

Brain ischemia is often accompanied by acute gastric lesions. To clarify the underlying mechanism, the influence of acute ischemic insult to the brain on gastric hemodynamics and mucosal integrity was examined in spontaneously hypertensive rats. One hour after brain ischemia, gastric mucosal blood flow decreased to 71% of the preischemic levels in the control rats but was preserved significantly better, at 94 and 108%, in the prazosin-treated and guanethidine-treated rats, respectively. Vagotomy almost abolished the decrease in gastric mucosal blood flow during cerebral ischemia. Intragastric 0.6 N hydrochloric acid administered just after reperfusion induced more severe hemorrhagic ulcers in the control than in the prazosin-treated and vagotomized groups. These results suggest that noradrenergic neurons acting through ₁-adrenoceptors contributes to the decrease in gastric mucosal blood flow, and the subsequent disturbed integrity of the gastric mucosa, through the vagal adrenergic pathway during brain ischemia in spontaneously hypertensive rats.     

High serum level of methylglyoxal-derived AGE, <Emphasis Type="Italic">N</Emphasis>δ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine,independently relates to renal dysfunction

Background

The dicarbonyl methylglyoxal reacts primarily with arginine residues to form advanced glycation end products, including Nδ-(5-hydro-5-methyl-4 -imidazolone-2-yl)-ornithine (MG-H1), which are risk factors for not only diabetic complications but also lifestyle-related disease including renal dysfunction. However, the data on serum level and clinical significance of this substance in chronic kidney disease are limited.

Methods

Serum levels of MG-H1 and Nε-(carboxymethyl) lysine (CML) in 50 patients with renal dysfunction were measured by liquid chromatography/triple-quadruple mass spectrometry.

Results

The median serum MG-H1 levels in patients with estimated glomerular filtration rate (eGFR) of ≥30, 15–30, and <15 ml/min/1.73 m² was 4.16, 12.58, and 14.66 mmol/mol Lys, respectively (p > 0.05). On the other hand, MG-H1 levels in patients with HbA1c of <6 and ≥6 % was 12.85 and 10.45 mmol/mol Lys, respectively, the difference between which is not significant. In logistic regression analysis, decreased renal function (eGFR <15 ml/min/1.73 m²) significantly associated with high serum levels of MG-H1 [odds ratio: 9.39 (95 % confidence interval 1.528–57.76), p = 0.015; Spearman rank correlation: MG-H1 vs. eGFR, r = ?0.691, p < 0.01]. In contrast, the serum level of CML did not correlate with eGFR, but correlated with systolic blood pressure [odds ratio 16.17 (95 % confidence interval 1.973–132.5), p = 0.010; Spearman rank correlation coefficient: CML vs. eGFR, r = 0.454, p < 0.01].

Conclusion

These results showed that the serum concentration of MG-H1 was strongly related to renal function rather than to DM.

     

A Morphological Study on Vascular Changes in the Surgically Resected Tissues of Temporal Lobe Epilepsy—with a Special Reference to the Etiology

• 1 Twenty-one out of 23 cases surgically resected specimens of TLE presented the common histological findings; sclerotic changes of the tissues. And the other two cases encountered the small tumors which might be called “cryptic.”
• 2 Since circulatory disturbance is generally accepted to explain the cause of TLE, we reexamined vascular behaviors in detail and found the quantitative and qualitative abnormalities which reached the high rate of 71% (17 out of 21 cases) except two cases of small tumors. Moreover, it is remarkably noteworthy that these vascular changes adjoin the sclerosed parenchymal tissue.
• 3 It may be said that vascular changes have exerted some influences on the formation of inferomedial temporal sclerosis from the standpoint of the histological findings, though they are alone not fully sufficient to explain the etiology of TLE.

     

Pediatric oncologic emergencies: Clinical and imaging review for pediatricians

Children with cancer are at increased risk of life‐threatening emergencies, either from the cancer itself or related to the cancer treatment. These conditions need to be assessed and treated as early as possible to minimize morbidity and mortality. Cardiothoracic emergencies encompass a variety of pathologies, including pericardial effusion and cardiac tamponade, massive hemoptysis, superior vena cava syndrome, pulmonary embolism, and pneumonia. Abdominal emergencies include bowel obstruction, intussusception, perforation, tumor rupture, intestinal graft‐versus‐host disease, acute pancreatitis, neutropenic colitis, and obstructive uropathy. Radiology plays a vital role in the diagnosis of these emergencies. We here review the clinical features and imaging in pediatric patients with oncologic emergencies, including a review of recently published studies. Key radiological images are presented to highlight the radiological approach to diagnosis. Pediatricians, pediatric surgeons, and pediatric radiologists need to work together to arrive at the correct diagnosis and to ensure prompt and appropriate treatment strategies.