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.     

Successful treatment for squamous cell carcinoma of the female urethra with combined radio- and chemotherapy

We report on two cases of women with locally advanced squamous cell carcinoma of the urethra. Patient 1 also displayed regional lymph node metastasis. Treatment comprised combined radiotherapy to 60 Gy and chemotherapy with 5-fluorouracil and cisplatin. Complete response was obtained in both patients, including the inguinal lymph nodes of Patient 1. Patient 1 experienced recurrent inguinal lymph node metastasis on the contralateral side at 42 months after initial treatment, and the same treatment was performed followed by surgical excision. Both patients remain alive with no evidence of disease, at 12 months after recurrence in Patient 1, and at 27 months after treatment in Patient 2.     

Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy

Hypertrophic cardiomyopathy and dilated cardiomyopathy are two major clinical phenotypes of “idiopathic” cardiomyopathy. Recent molecular genetic analyses have now revealed that “idiopathic” cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. A hypertrophic cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic cardiomyopathy and dilated cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.     

Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (OECD): Familiarization Using Cyclophosphamide

Combined Repeat Dose and Reproductive/Developmental ToxicityScreening Test (OECD): Familiarization Using Cyclophosphamide.TANAKA, S., KAWASHIMA, K., NAITO, K., USAMI, M., NAKADATE, M.,IMAIDA, K., TAKAHASHI, M., HAYASHI, Y., KUROKAWA, Y., AND TOBE,M. (1992A, Y., AND TOBE, M. (1992). Fundam. Appl. Toxicol. 18,89–95. A familiarization study was conducted on the "Combined RepeatDose and Reproductive/Developmental Toxicity Screening Test(ReproTox)" proposed by the OECD. Cyclophosphamide (CP) at dosesof 6.7, 4.5, 3, 2, and 0 mg/kg body wt was given daily by gavageto groups of 12 male and 12 female Sprague-Dawley rats. As aresult, anemia and leukopenia were evident in treated males.The absolute and relative thymus and spleen weights were decreasedin treated rats. Histopathologically, atrophy of the thymus,spleen, and bone marrow was observed. With respect to the reproductive/developmentaltoxicity, dose-dependent increases in postimplantation lossof fetuses and postnatal death were found in dams given CP.The body weight of pups treated with CP was significantly loweredin a dose-related manner. Thus the results demonstrated mostof the known toxicological properties of CP, except the adverseeffects on spermatogenesis and fertility. Therefore ReproToxcan be considered as a useful screening test for assessing repeatdose and reproductive/developmental toxicity of existing chemicalsof high production volume.     

Preoperative Characteristics of Auditory Brainstem Response in Acoustic Neuroma with Useful Hearing: Importance as a Preliminary Investigation for Intraoperative Monitoring

We classified the results of preoperative auditory brainstem response (ABR) in 121 patients with useful hearing and considered the utility of preoperative ABR as a preliminary assessment for intraoperative monitoring. Wave V was confirmed in 113 patients and was not confirmed in 8 patients. Intraoperative ABR could not detect wave V in these 8 patients. The 8 patients without wave V were classified into two groups (flat and wave I only), and the reason why wave V could not be detected may have differed between the groups. Because high-frequency hearing was impaired in flat patients, an alternative to click stimulation may be more effective. Monitoring cochlear nerve action potential (CNAP) may be useful because CNAP could be detected in 4 of 5 wave I only patients. Useful hearing was preserved after surgery in 1 patient in the flat group and 2 patients in wave I only group. Among patients with wave V, the mean interaural latency difference of wave V was 0.88 ms in Class A (n = 57) and 1.26 ms in Class B (n = 56). Because the latency of wave V is already prolonged before surgery, to estimate delay in wave V latency during surgery probably underestimates cochlear nerve damage. Recording intraoperative ABR is indispensable to avoid cochlear nerve damage and to provide information for surgical decisions. Confirming the condition of ABR before surgery helps to solve certain problems, such as choosing to monitor the interaural latency difference of wave V, CNAP, or alternative sound-evoked ABR.     

A Simple, 10-minute Procedure for Transforaminal Injection under Ultrasonic Guidance to Effect Cervical Selective Nerve Root Block

The aim is to provide a detailed procedure of a simple and 10-minute cervical nerve root block (CNRB) under ultrasonic guidance, and to report the clinical outcomes, disorders, and complications. Records of patients who had undergone CNRB, were reviewed under ultrasonic guidance at the hospital from 2010 through 2012. The procedure is described in detail. Arm and shoulder pain was evaluated by use of the visual analogue scale (VAS). Forty-three patients agreed to undergo CNRB under ultrasonic guidance. Nerve roots from C5 to C8 were affected in 41, and these nerve roots were readily distinguished. Two of the 43 participants did not receive injections because impediments in visualizing the affected nerve root. Of the 41 who received injections, radicular pain immediately disappeared in 39, who continued to feel pain relief 1 month later. However, pain recurred in 15 patients (38%), of whom 11 underwent cervical spine surgery. The rest of 24 patients felt sustained pain relief longer than 3 months after the injection, significantly. Although one patient had recurrent radicular pain 10 months later, the pain could be controlled by medication. At the final follow-up periods, 17.2 (10–24 months), the median VAS score of the patients, 23 (0 to 71 mm), was significantly improvement (P = 0.001) in comparison to before injection 88 (range; 56–100). No complications occurred. The cervical nerve root block under ultrasonic guidance simply, safely, and efficaciously decreased radicular pain for 17.2 months in 62% patients with intolerable radicular pain.     

Serum hyaluronic acid reflects the effect of interferon treatment on hepatic fibrosis in patients with chronic hepatitis C

Changes in serum hyaluronic acid (HA) in 35 patients treated with interferon (IFN) were studied and the histological change in fibrosis was analysed. Serum HA levels and hepatitis C virus (HCV) RNA were followed from the start of therapy to 12 months after completion of treatment. Histological changes in pre- and post-treatment liver biopsies were assessed using a modified Knodell's scoring system. The serum levels of HA (r = 0.79; P<0.0001) correlated with the degree of fibrosis more closely than with that of amino terminal peptides of type III procollagen (PIIIP; r = 0.45; P<0.05) or type IV collagen (IV-C; r = 0.42; P<0.05). Only complete responders (CR) had a significant decrease in serum levels of HA and IV-C (P<0.05), in parallel with histological improvement (P<0.01). Neither partial responders (PR) nor non-responders (NR) had significant changes in histological scores and in serum levels of fibrotic markers. Significant differences were observed between CR and NR, both in HA levels (P<0.01) and PIIIP levels (P<0.05) 12 months after the cessation of treatment. These results suggest that serum HA is an indicator of the extent of fibrosis in chronic hepatitis C. Serial determinations of serum HA levels may be of use for monitoring the histological response of hepatic fibrosis to IFN treatment in chronic hepatitis C.     

Work and family characteristics as socioeconomic determinants in long sickness absence: the Japanese civil servants study

Long sickness absence is more common among low socioeconomic status (SES) groups than high SES groups. This study aimed to evaluate whether work and family characteristics contribute to SES and sex differences in long sickness absence (7 days or more). The participants were 3080 civil servants working for a local Japanese government. In both sexes, low-grade employees were likely to take long sickness absence, with a statistically significant association for men (age-adjusted OR of lowest-grade employees for long sickness absence: 2.30 (95% Confidence Interval (CI): 1.32–4.02)). After adjusting for all variables, SES differences in long sickness absence in men decreased to OR 1.98 (CI 1.10–3.55) but remained significant; in men, being without a spouse was significantly associated with long sickness absence. Employees working long hours had lower OR for long sickness absence after adjusting for all variables in both sexes. Conversely, poor sleep quality and longstanding illness significantly increased OR for long sickness absence. In conclusion, SES differences in sickness absence were explained partly by work and family characteristics, longstanding illness, and poor sleep quality; however, other factors that were not evaluated in this study may also be associated with SES differences.