Irinotecan+cisplatin and irradiation are effective for brain metastases of gastric cancer--two case reports

We treated two patients in whom irinotecan (CPT-11)+cisplatin (CDDP) and irradiation showed efficacy against brain metastases of gastric cancer. CPT-11 and CDDP were administered on days 1 and 15 of a 28-day cycle at 60 mg/m(2) and 30 mg/m(2), respectively. The first patient was a 63-year-old man,who complained of headache and weakness. In March 2003, he was diagnosed as having Stage IV gastric cancer with peritoneal dissemination (T3, Nx, P1) and underwent total gastrectomy with D1 dissection. Chemotherapy with S-1 was continued after surgery. Two years and two months later, a metastatic tumor was found in the upper lobe of the right lung. The protocol was changed to S-1+CDDP, but progression of his disease occurred. The weekly paclitaxel (PTX) therapy was tried instead. Seven months later, he developed headache and weakness, and multiple brain metastases were diagnosed by CT scanning. We performed total brain irradiation (30 Gy) and started CPT-11+CDDP therapy, which was continued on a fortnightly basis at 60 mg/m(2) and 30 mg/m(2), respectively. The brain metastases regressed (PR), and this therapy led to a marked improvement in his quality of life. The second patient was a 78-year-old man, who complained of weakness of the lower extremities and dizziness. In November 2003, he was diagnosed as having stage IB gastric cancer (T2 (ss), N0, P0), and underwent total gastrectomy and splenectomy with D2 dissection. One year and four months later, local recurrence at the anastomosis was detected, as well as a metastatic tumor in the right lung. S-1, S-1+CDDP, and weekly PTX therapy were all tried. One year later, the patient was admitted with weakness and dizziness,and brain metastases were detected by CT scanning. We then performed Cyber Knife treatment and administered CPT-11+CDDP. As a result, his brain metastases partially regressed (PR).     

Comparative studies on effect of risedronate and alfacalcidol against glucocorticoid-induced osteoporosis in rheumatoid arthritic patients

Osteoporosis is a common adverse reaction induced by glucocorticoid treatment. Bisphosphonate, vitamin D(3) (VD(3)) or vitamin K(2) (VK(2)) is recommended as first or second choice of drug for treatment of glucocorticoid-induced osteoporosis. In the present study, the treatment effect of risedronate against glucocorticoid-induced osteoporosis in rheumatoid arthritic patients was compared with that of alfacalcidol. Twelve patients were randomized to receive either risedronate (2.5 mg) or alfacalcidol (0.5 microg) daily for 48 weeks. Each patient also received 800 mg of calcium supplementation (800 mg/day) daily. Bone mineral density (BMD) and the biochemical markers of bone turnover were measured before (baseline) and 12, 24, and 48 weeks after treatment with risedronate or alfacalcidol, and the percentage changes in these parameters from baseline were compared.The BMD values 12, 24 and 48 weeks after treatment with risedronate increased by 3.9%, 4.1% and 5.2%, respectively, which were significantly higher than those after treatment with alfacalcidol (2.8%, 2.1% and 2.5%, respectively). Urinary excretion of N-telopeptides of type I collagen and deoxypyridinoline after risedronate treatment were more significantly decreased than that after alfacalcidol treatment. The present findings at least suggest that risedronate is more useful for the prevention and treatment of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis than alfacalcidol, although the number of patients studied was small.     

Brain metastases from urachal carcinoma

We present a case of brain metastases of the urachal carcinoma, which is extremely rare and malignant. Contrast-enhanced MRI was employed to detect them. A large mass was removed surgically and 4 other small metastases were treated by gamma knife radiosurgery. Six weeks after radiosurgery, the 4 lesions had disappeared on MRI. We emphasise the importance of early diagnosis using MRI and treatment by radiosurgery for this rare condition.     

Day-by-day variability of home blood pressure in patients with chronic kidney disease

PURPOSE: We examined the characteristics of the day-by-day variability of home blood pressure (HBP) in patients with chronic kidney disease (CKD). METHODS: We obtained HBP recordings from 368 CKD patients (63+/-13 years, eGFR 34+/-23 mL/min/1.73 m2, males 253). The day-by-day variability of HBP was defined as the coefficient of variation (CV) values of BP measurements every morning after waking and every evening before sleeping on 7 consecutive days. In a portion of the patients, the CV values of HBP were collected every 6 months during a 2-year period and the association with a decline in GFR was examined. RESULTS: CV values of morning/evening systolic BP (SBP) were 5.4+/-2.4%, 6.1+/-2.9 % (p<0.01). The CV values of morning SBP in females or patients with diabetic nephropathy (DN) were significantly greater than those in males or patients without DN, respectively (females 5.9+/-2.3%, males 5.2+/-2.4%, p< 0.01, DN 6.1+/-2.8 %, non DN 5.2+/-2.2 %, p<0.05). Multivariate linear regression analysis showed that female gender, DN, the number of antihypertensive drugs, higher heart rate and higher CV values of heart rate were associated with higher CV values of the morning SBP. CV values of the morning SBP showed no significant change during the 2-year period (0; 5.4+/-2.6%, 1 year; 5.3+/-2.9%, 2 years 5.6+/-3.1%, n=200). There was no significant difference in the change in eGFR between a group with high CV values (greater than 5 %) and a group with low CV values (lower than 5 %) during the 2-year period. CONCLUSIONS: In CKD patients, the day-by-day variability of HBP tended to be greater in the evening, in female and DN patients. There was no significant association between the day-by-day variability of HBP and decline rate in eGFR. Further studies are needed to clarify the clinical significance of the day-by-day variability of HBP in CKD patients.     

The anti-pruritic efficacy of TS-022, a prostanoid DP1 receptor agonist, is dependent on the endogenous prostaglandin D2 level in the skin of NC/Nga mice

TS-022 is a prostanoid DP(1) receptor agonist, originally developed as a novel anti-pruritic drug for atopic dermatitis. The drug has been shown to suppress scratching and improve the skin inflammation in the NC/Nga (NC) mouse, a model of atopic dermatitis. Corticosteroids are commonly used as effective agents for the treatment of atopic dermatitis. We examined the anti-pruritic efficacy of TS-022 in NC mice cohabited with skin-lesioned NC mice, which showed spontaneous scratching without skin lesions in the early phase and chronic itching with severe dermatitis in the late phase, in comparison with that of dexamethasone. We have previously reported that prostaglandin D(2) might have a physiological role in the inhibition of pruritus. While after 2 weeks of cohabitation with skin-lesioned NC mice (early phase of dermatitis, characterized by the appearance of spontaneous scratching), topically applied TS-022 exhibited a weak anti-pruritic effect in the NC mice, after 6 weeks of cohabitation (late phase, characterized by both chronic scratching and dermatitis), the drug exerted potent anti-pruritic activity. In contrast, dexamethasone exerted potent anti-pruritic effect in both the early and late phases. Indomethacin aggravated the scratching in the early phase, but had no effect in the late phase. The skin prostaglandin D(2) level was significantly increased in the early phase, to subsequently declined and return to the basal level in the late phase. The cutaneous ability for prostaglandin D(2) production following topical application of arachidonic acid or mechanical scratching was decreased in the late phase. Moreover, the expression level of the prostanoid DP(1) receptor in the skin was increased in the late phase. These findings suggest that the potent anti-pruritic activity of TS-022 in the late phase might be attributable to the decrease of endogenous prostaglandin D(2) production and increase of prostanoid DP(1) receptor expression.     

Efficacy of Enalapril after ineffective theophylline treatment on erythrocytosis after renal transplantation

Erythrocytosis represents a common complication in renal allograft recipients. Traditional therapies including phlebotomy and bilateral native nephrectomies are cumbersome for both the clinical personnel and the patient. Recently, pharmacological agents such as angiotensin converting enzyme inhibitor and theophylline have been proposed as effective therapies for post-transplant erythrocytosis (PTE). We have treated a PTE patient successfully with enalapril without any side effects and renal dysfunction after theophylline treatment showed no improvement in PTE. A decline in Ht levels was independent of the changes in Epo levels during enalapril treatment. Although the mechanism underlying the beneficial effect of enalapril remains undetermined, enalapril is recommended for the initial treatment of PTE.     

Hemodynamic effects of induced hypotension by ketanserin in anesthetized dogs]

Hemodynamic effects of hypotension induced by ketanserin were investigated in 18 mongrel dogs under 0.87% halothane in oxygen (1 MAC). They were randomly allocated to one of two groups. Group C (n = 9) received no vasodilator therapy and served as a control and group K (n = 9) received 0.1% ketanserin solution. Mean arterial pressure decreased and was maintained at 60 mmHg for 60 minutes in group K. No change was noted in hemodynamic variables measured in group C throughout the experiment. During and after induced hypotension in group K, stroke volume index increased significantly compared with the control value. On the other hand, systemic vascular resistance was significantly reduced, reaching 50% of the control value at the end of the hypotensive period. Left ventricular maximum dp/dt showed a significant reduction during hypotension but then increased gradually to the control value. In addition, heart rate decreased significantly during and after induced hypotension, therefore these vasodilator effects were not accompanied by reflex tachycardia. Cardiac index remained unchanged throughout the experiment. Further, no changes in central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure and pulmonary vascular resistance were observed. In conclusion, the data indicate that ketanserin is a potent systemic vasodilator producing stable hemodynamics. It also reduces systemic vascular resistance without reflex tachycardia and this is a favorable effect of ketanserin.     

Pulmonary exposure to diesel exhaust particles enhances fatty change of the liver in obese diabetic mice

In epidemiological studies, exposure to ambient particulate matter (PM) has been reported to be positively associated with mortality in subjects with diabetes mellitus. Diesel exhaust particles (DEP) are major constituents of atmospheric PM. However, there is no experimental evidence for the relation of DEP to diabetes mellitus and its complications. We investigated the effects of DEP inoculated intratracheally on diabetic changes and nonalcoholic fatty liver disease (NAFLD) in diabetic obese and control mice. db/db mice and the corresponding nondiabetic db/+m mice received exposure to vehicle or DEP every two weeks. Animals were examined with biochemistry, histology, and immunohistochemistry for hexanoyl-lysine (HEL) in the liver. In the db/+m mice, pulmonary exposure to DEP did not increase levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) compared to that to vehicle. In the db/db mice, however, the exposure to DEP increased the levels of AST and ALT compared to that to vehicle. Only in the db/db mice, DEP enhanced the magnitude of steatosis and formation of HEL, a marker of oxidative stress, in the liver compared to vehicle. These results suggest that pulmonary exposure to DEP, PM, enhances steatosis in the liver of obese diabetic subjects possibly via enhanced oxidative stress.     

Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice

OBJECTIVE: Effective approaches should be established to prevent the onset of type 2 diabetes mellitus, which has been increasing in developed countries. The present study examined whether dietary supplementation with cacao liquor proanthocyanidins (CLPr) could prevent elevation of blood glucose levels in mice with diabetes mellitus and obesity. METHODS: C57BL/KsJ-db/db (db/db) diabetic obese mice and C57BL/KsJ-db/+m (db/+m) control mice were fed a diet containing 0% w/w CLPr (0% CLPr), 0.5% w/w CLPr (0.5% CLPr), or 1.0% w/w CLPr (1.0% CLPr) from age 3 wk to age 6 wk. Levels of blood glucose were measured at 4 and 5 wk of age. The animals were sacrificed and the levels of blood glucose and fructosamine were measured at 6 wk of age. RESULTS: The levels of blood glucose and fructosamine were higher in the db/db mice than in the db/+m mice fed a diet containing 0%, 0.5%, or 1.0% CLPr. In the db/+m mice, the levels of blood glucose or fructosamine were not significantly different across animals fed 0% CLPr, 0.5% CLPr, and 1.0% CLPr. In the db/db mice, however, a diet containing 0.5% or 1.0% CLPr decreased the levels of blood glucose and fructosamine compared with that containing 0% CLPr without significant effects on body weights or food consumption. CONCLUSION: Dietary supplementation with CLPr can dose-dependently prevent the development of hyperglycemia in diabetic obese mice. The dietary intake of food or drinks produced from cacao beans might be beneficial in preventing the onset of type 2 diabetes mellitus.     

QOL assessment after palliative surgery for malignant bowel obstruction caused by peritoneal dissemination of gastric cancer: a prospective multicenter observational study

Background

Patients with peritoneal dissemination of gastric cancer have poor oral intake caused by malignant bowel obstruction (MBO). Palliative surgery has often been undertaken to improve quality of life (QOL), but few prospective studies on palliative surgery in this patient population have been published.

Patients and methods

We prospectively investigated the significance of palliative surgery using patient-reported QOL measures. Patients underwent palliative surgery by small intestine/colon resection or small intestine/colon bypass or ileostomy/colostomy for MBO. The primary endpoint was change in QOL assessed at baseline, 14 days, 1 month, and 3 months following palliative surgery using the Euro QoL Five Dimensions (EQ-5D?) questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications.

Results

Between April 2013 and March 2018, 63 patients were enrolled from 14 institutions. The mean EQ-5D? utility index baseline score of 0.6 remained consistent. Gastric-specific symptoms mostly showed statistically significant improvement from baseline. Forty-two patients (67%) were able to eat solid food 2 weeks after palliative surgery and 36 patients (57%) tolerated it for 3 months. The rate of overall morbidity of?≥?grade III according to the Clavien–Dindo classification was 16% (10 patients) and the 30-day postoperative mortality rate was 3.2% (2 patients).

Conclusions

In patients with MBO caused by peritoneal dissemination of gastric cancer, palliative surgery did not improve QOL while improving solid food intake, with an acceptable postoperative morbidity and mortality rate.