Analysis of the circumstances at the end of life in children with cancer: Symptoms, suffering and acceptance

BACKGROUND: In an effort to improve the quality of life of children with cancer, this study analyzes the signs and symptoms at the end of life in such children. It is hoped that these data will contribute to the development of appropriate programs to address the challenges faced by these children. PROCEDURE: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital, Japan. The circumstances, signs and symptoms at the end of life of these children were analyzed through their medical records. RESULTS: Of the 28 children, the underlying diseases were leukemia/lymphoma (LL group; n=11), brain tumors (BT group; n=7), and other solid tumors (OST group; n=10). Records showed poor appetite (100%), dyspnea (82.1%), pain (75.0%), fatigue (71.4%), nausea/vomiting (57.1%), constipation (46.4%) and diarrhea (21.4%) among these children. Anxiety was reported in 53.6% of the entire group of 28 children; however, no child in the BT group manifested anxiety. However, disturbance of consciousness was reported in all children in the BT group, which was significantly greater than in the other groups. Awareness, fear or acceptance of the imminence of his/her own death as indicated by verbal expression was reported in nine children (32.1%). CONCLUSIONS: Using the data obtained in the present study, we describe situations faced in the terminal care of children. It is important to address the problems revealed by this analysis in order to achieve improvements in both the physical and psychological care of children with terminal cancer.     

Influence of left ventricular filling proffle during preceding control beats on pulse pressure during ventricular premature contractions

We investigated whether the left ventricular filling profile,defined as the early to late diastolic left ventricular fillingvolume ratio, during the preceding control beats actually affectsthe pulse pressure during a ventricular premature contraction(PVC). Twenty patients underwent invasive electrophysiologicalstudy for sinus bradycardia. VPCs with various coupling intervalswere induced by right ventricular electrical stimulation, andthe mitral filling flow velocity pulsed Doppler echocardiography,the femoral arterial pressure curve and the electrocardiogramwere simultaneously recorded The early to late diastolic velocity-rimeintegral ratio (E₁/A₁ ratio) of the mitral filling flow velocityduring the control beats which preceded the VPC was measuredas an index characterizing left ventricular filling profile.The coupling interval of each VPC and the extrasystolic beatpulse pressure were measured The ratio of the extrasystolicbeat pulse pressure to the control beat pulse pressure was expressedin % (% extrasystolic beat pulse pressure). The correlationbetween the coupling interval and the % extrasystolic beat pulsepressure was investigated. Coupling intervals of 0·80,0·70, 0·60, 0·50, and 0·45 s wereused At a coupling interval of 0·80 or 0·45 s,the % extrasystolic beat pulse pressure showed no significantcorrelation with the E₁/A₁ ratio. In contrast, the % extrasystolicbeat pulse pressure with coupling intervals of 0·70,0·60, and 0·50 s showed a significant positivecorrelation with the E₁/A₁ ratio (r=0·67, 0·74,and 0·66 P<0·01, respectively). In additionto the prematurity and the site of origin of the VPCs, the leftventricular filling profile during the preceding control beatsmay significantly affect the height of the pulse pressure duringextrasystoles with medium length coupling intervals.     

THE IMPACT OF DIABETES MELLITUS ON THE PROGNOSIS OF ALCOHOLICS

In this study, the mortality of clinically treated Japanesealcoholics with diabetes mellitus was analysed. Fifty-one diabeticalcoholics without liver cirrhosis (DM), 23 diabetic and cirrhoticalcoholics (DM LC), 44 cirrhotic alcoholics without diabetes(LC), and 354 alcoholics without either complication (AL) admittedto the National Institute on Alcoholism in 1985 were studied.Thirty-seven diabetics required insulin treatment, and 12 oralhypoglycemic agents. The 4.4-year survival and drinking statusafter discharge were studied in 1990. Stepwise logistic regressionanalysis showed that the estimated odds for death increased8.10, 4.38, 3.70, and 3.27 times for the subjects with the alcoholmisuse after discharge, DM, DM LC, and LC, respectively. The4.4-year survival rate of alcoholics who continued misusingalcohol was much lower in DM (26%, P < 0.0005) and LC (35%,P < 0.0001) than in AL (73%). The survival rate of thosewho stopped misusing alcohol was significantly higher in DM(90%, P < 0.0001), LC (88%, P < 0.0001) and AL (94%, P< 0.0005) than those who continued misusing alcohol. Therewas no significant difference in the survival rate between thealcoholics with DM LC who continued misusing alcohol (50%) andthose who stopped misusing alcohol (73%). In the dead patients,56% of DM died unexpectedly or suddenly, whereas 71% of LC diedof liver failure after hospitalization. These results suggestthat diabetic alcoholics should be intensively educated forabstinence.     

Studies on Duodenal Cyclic AMP Content in Pancreatic Disease after Administration of Pancreozymin and Secretin

Cyclic AMP (cAMP) output in the duodenal contents of 11 normal subjects, 18 patients with chronic pancreatitis, six convalescing from acute pancreatitis and five with pancreatic carcinoma was measured after a single dose of pancreozymin and secretin. The technic was indirect, utilizing recovery of duodenal contents by the Dreiling tube rather than direct measurements of fluid that was not contaminated by bile. In all patients groups, cAMP output reached a peak after this stimulation with a concomitant increase of bicarbonate and amylase outputs. A significantly decreased cAMP output was observed in all pancreatic disease groups compared to the normal group. Patients with chronic pancreatitis showed a slightly decreased cAMP output, considerably decreased bicarbonate output and normal amylase output. In acute pancreatitis cAMP output was reduced with normal bicarbonate and amylase outputs. In pancreatic carcinoma cAMP decreased significantly, bicarbonate output was moderately reduced and amylase output was normal. cAMP output in all groups studied did not correlate with either bicarbonate output or amylase output.     

Specific IgE antibodies and serum eosinophil cationic protein in children with atopic dermatitis alone

Both eosinophils and specific immunoglobulin E (IgE) to foods and mites have been considered involved in the pathogenesis of atopic dermatitis (AD). The relationship between eosinophils and specific IgE, however, remains to be elucidated. Blood eosinophil counts, serum eosinophil cationic protein (ECP) and IgE to egg white, cow's milk, soybean, rice and Dermatophagoides pteronyssinus (Dp) were measured in subjects with AD alone or bronchial asthma (BA) alone. Subjects with positive IgE titers (Pharmacia radioallergosorbent test (RAST) units > 0.7) of one or more items were defined as RAST-positive. Immunoglobulin E titers to egg white, cow's milk and soybean of subjects with AD were high in early childhood and declined with aging, whereas the titers of subjects with BA were negative or low. Immunoglobulin E titers to Dp were elevated after 1 year of age in both disease groups. Eosinophil cationic protein (ECP) levels and blood eosinophil counts in the AD and BA groups were significantly higher than those of non-atopic controls. No difference in ECP levels or blood eosinophil counts were observed between RAST-positive and negative groups. It is concluded that IgE to foods such as egg white, cow's milk and soybean might have a role in the pathogenesis of AD of young children, while IgE to mites might be involved in older children. Eosinophils may also participate in AD. However, different mechanisms may be responsible for the rise in specific IgE and high ECP levels and blood eosinophil counts.     

Comparison of statistical power between 2×2 allele frequency and allele positivity tables in case-control studies of complex disease genes

In case-control studies of complex disease genes, allele frequencies or allele positivities at candidate loci or markers are compared between cases and controls. Although 2 × 2 contingency tables based on allele frequency and allele positivity are generally used to perform simple statistical tests (e.g. a comparison of two proportions and a χ² test), little is known about the difference in power between the two tables. In this study, we investigated the number of subjects required to obtain a power of 1 −β with a significance level of α for the allele frequency and allele positivity tables. A large difference in the required number of subjects was found between the two tables. Allele positivity tables were suitable for the detection of susceptibility alleles showing a dominant mode of inheritance (MOI). On the other hand, allele frequency tables were suitable for the identification of susceptibility alleles showing a recessive MOI or a multiplicative MOI. In the case of an additive MOI, a suitable table was determined by combining the frequency of the susceptibility allele and the penetrance. These results imply that there are cases in which true association is detected based on one contingency table and is not detected based on another. A simulation analysis revealed that the type I error rate was not much inflated under the null hypothesis of no association, even when a statistical test was performed twice using both allele frequency and allele positivity tables. In contrast, under the alternative hypothesis, the loss of power was marked when a test was performed once using an unsuitable table. In conclusion, statistical tests should be performed using both tables, without adjustment of multiplicity, in case-control studies of complex disease genes when the study objective is exploratory.     

Clinical pharmacological study of a plasma‐derived factor VIIa and factor X mixture (MC710) in haemophilia patients with inhibitors – Phase I trial

Summary. MC710, a combined product of plasma‐derived activated factor VII (FVIIa) and factor X (FX) at a protein weight ratio of 1:10, is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In this study, pharmacokinetic (PK), pharmacodynamic (PD) parameters and safety of single doses of MC710 were investigated in 11 male haemophilia patients with inhibitors in a non‐bleeding state. This was a multi‐centre, open‐labelled, non‐randomized, active controlled crossover, dose‐escalation study of five doses (20–120 μg kg⁻¹ of FVIIa) with re‐administration of different MC710 dosages to the same subjects. The active controls were NovoSeven (120 μg kg⁻¹) and/or FEIBA (50 and 75 U kg⁻¹) which were used to compare PD parameters. The area under the curve (AUC) and maximum plasma concentration (C_max) of MC710 active ingredients increased dose‐dependently within the range of 20 and 120 μg kg⁻¹. After administration of MC710, activated partial thromboplastin time (APTT) was dose‐dependently improved and prothrombin time (PT) was shortened to approximately 6 s at 10 min, and APTT improvement and PT shortening effects were maintained until 12 h after administration of MC710 at all doses. No serious or severe adverse event was observed after administration of MC710; furthermore, several diagnostic marker values and those changes did not indicate any signs of disseminated intravascular coagulation (DIC). These results suggest that MC710 would have haemostatic potential equal to or greater than NovoSeven and FEIBA and was be tolerable when given at doses up to 120 μg kg⁻¹.     

Acute Urinary Tract Toxicity of Tetraethylorthosilicate in Rats

Acute stomach, kidney, and bladder toxicity was evaluated inF344 rats after gastric gavage of tetraethylorthosilicate (TES)at daily doses of 0, 0.111, 0.223, and 0.333 g. Five rats ofeach sex at each dose were sacrificed after 1, 2, and 4 days.In TES-treated groups, silicate accumulated in the stomach glandsand the muscle layer of the forestomach and glandular stomach.Serum chemistries demonstrated acute onset of renal failure.In the kidneys, acute tubular necrosis, accumulation of silicates,and superficial necrotizing papillitis were observed. In therenal pelvis and bladder, there was urothelial simple hyperplasia,focal erosion of the mucosa, edema, and inflammation. Theseacute toxic changes were dose and time dependent, but significantsex differences were not observed. The microscopic changes inthe urothelium were similar to those observed following administrationof high doses of sodium saccharin to male rats in which urinarysilicate precipitate and crystals form.     

Solitary juvenile polyp developing adenocarcinoma with submucosal invasion

Solitary juvenile polyps are generally non‐neoplastic hamartomatous polyps. Inflammation is suggested as the cause of proliferation and progression of these polyps, and adenomatous and carcinomatous changes are rare. We report a rare case of a solitary juvenile polyp with malignant transformation that developed in the sigmoid colon of a 12‐year‐old boy. A 3 cm, pedunculated polyp was endoscopically resected, and histologic evaluation revealed the characteristic features of a juvenile polyp. However, mucous‐filled ectatic glandular spaces were lined by mucin‐secreting columnar epithelial cells with atypical change, and an admixture of adenocarcinoma invading the submucosa was confirmed. The histologic features may suggest the involvement of the adenoma–carcinoma sequence in the development of adenocarcinoma in the present case. Although rare, solitary juvenile polyps should develop adenocarcinoma and thorough histologic evaluation of the resected polyps is warranted to identify the adenomatous tissue.     

A Case of Early Gastric Cancer Manifesting as a Submucosal Tumor

Abstract: Gastric cancer manifesting as a submucosal tumor (SMT) is not common. A gastric barium meal and endoscopic studies performed on a 49-year-old male with epigastric pain, revealed an elevated lesion with bridging folds and central depression on the posterior wall of the lower body. An endoscopic ultrasonography (EUS) revealed a hypoechoic mass lesion within the submucosal layer. Due to an increase in the size of the tumor and its central depression during the subsequent year and a half, the patient was admitted for closer examination. Endoscopic biopsy material from the deeper layer, obtained by mucosal resection, revealed a poorly differentiated adenocarcinoma. Microscopic examination of the resected stomach showed a poorly differentiated adenocarcinoma within the submucosal layer, with considerable lymphocyte infiltration. Immunohistological examination disclosed marked T cell infiltration adjacent to the cancer cells. We suggest that considerable lymphocyte infiltration, particularly T cells, may have some role in the protective reaction against cancer cells. Our case was diagnosed as being cancer 18 months after the first endoscopic study. The biopsy material taken from the depression at the time of the first examination showed benign findings and a EUS revealed typical SMT. In the case of SMT shown by EUS to be a hypoechoic mass lesion in the submucosal layer, it is recommended that biopsy material be obtained from the deeper layer using methods available such as artificial ulcer formation.