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.     

Low-pressure Pneumoperitoneum for Laparoscopic Surgery Using a Disposable,Flexible Abdominal Wall Retractor

Abstract: Since April 1991, we have studied 160 patients who had had a successful laparoscopic cholecystectomy. Nine patients who presented with chronic cholecystitis with severe local adhesion and who were also considered to require a longer operative time were selected as suitable candidates for this procedure. They were successfully treated under a zero- to four-mmHg low-pressured pneumoperitoneum procedure combined with total abdominal wall lifting using a disposable, flexible vinyl tube retractor. This method enabled exactly the same clear laparoscopic vision as is possible in the routinely-used high-pressure pneumoperitoneum even in the marginal portions of the abdominal cavity. Moreover, it facilitated early reinsufflation after the cauterization-produced smoke was exhausted, which minimized the operative time and reduced the surgeon's anxiety concerning the maintenance of a sufficiently airtight condition. We believe that this low-pressure pneumopeqitoneum procedure also benefits the poor-risk patient who has restricted cardiopulmonary function, especially during advanced laparoscopic surgery which requires a longer operative and anesthetic time.     

Production of IL-6 by T cells from the femoral head of patients with rapidly destructive coxopathy (RDC)

RDC is a syndrome with unknown etiology that causes rapid destruction of a hip joint. We have investigated the production of osteoclast-activating cytokines (IL-6, IL-1α and tumour necrosis factor-alpha (TNF-α)), interferon-gamma (IFN-γ) and IL-8 by T cells in the affected joint. The level of IL-6 produced by the T cell lines (TCL) established from the femoral head was significantly higher than that from patients' or healthy donors' peripheral blood mononuclear cells (PBMC). IL-6 production by the TCL from synovial membrane or from patients' PBMC was also significantly higher than that from healthy donors' PBMC. IL-1α production by the TCL from the femoral head was significantly higher than any of the other groups when all the TCL were used for the analysis. TNF-α production was highest in the TCL from patients' PBMC. The levels of IFN-γ or IL-8 were not significantly different among these four groups. The plasma levels of all these cytokines except for IFN-γ, that was rather lower, in RDC patients were not significantly different from those in osteoarthrosis or trauma patients, or healthy donors. These results suggest that T cells at the affected femoral head, and also synovial membrane to some extent, are involved in bone resorption through the production of IL-6 and probably IL-1α in patients with RDC.     

A Case of Pneumocytoma (So-Called Sclerosing Hemangioma) With Lymph Node Metastasis

A case of "sclerosing hemangionia" (pneumocytoma) of the lungwith lymph node metastasis is reported. A 22-year-old Japaneseman was found to have a well-defined round lesion in the rightlung (S⁷), which increased in size slightly during a 2-yearfollow-up period. He underwent right lower lobectomy with a preoperative diagnosisof a benign lung tumor. The pulmonary tumor revealed histologicalfeatures characteristic of "sclerosing hemangioma" of the lung,in addition to which there were many large polygonal foamy cells,forming tubular or papillary structures. These cells were foundby electron microscopy to contain numerous cytoplasmic lamellarbodies and showed a positive reaction with anti-surfactant apoproteinantibody immunohistochemically. Therefore, they were consideredto be cells differentiating toward type II pneumocytes. Reviewof 21 typical "sclerosing hemangionia" disclosed a few or somesuch foamy cells in 10 cases. A single hilar lymph node wasthe site of microscopic metastases, which consisted of "largeclear foamy cells" and smaller polygonal or round cells withslightly eosinophilic cytoplasm, both of which were componentsof the pulmonary "sclerosing hemangioma" This case supportsthe theory that "sclerosing hemangioma" is a neoplasm of typeII pneumocyte lineage. Although it is said to be benign, rarecases apparently show metastatic potential.     

Risk Factor Analysis of Facet Fusion Following Cervical Lateral Mass Screw Fixation with a Minimum 1-Year Follow-up: Assessment of Maximal Insertional Screw Torque and Incidence of Loosening

Posterior stabilization is a common surgical procedure, which aims for rigid stabilization by facet fusion. Facet non-union has a potential risk of the screw loosening and malalignment. Although some authors have reported the influencing factors about screw loosening in the lumbar spine, there are few reports about the risk factor contributing to the facet non-union in the cervical spine. In all, 22 patients (78 facets and 122 screws) with degenerative cervical kyphosis or spondylolisthesis who underwent decompression and lateral mass screw (LMS) fixation were analyzed. Age, gender, smoking, bone mineral density (BMD), the degree of facet decortication with bone packing, and screw loosening were investigated as risk factors contributing to the facet non-union at each segmental fused level. Facet fusion rate was 85.9% (67/78 facets) and the incidence of loosening was 4.9% (6/122 screws, 4 patients). Insufficient facet decortication with bone packing is a significant risk factor of facet non-union (p <0.05, odds ratio: 26.5). All six loosened screws were associated with bony non-union of the facet and were located in the uppermost or lowermost vertebrae. Comparing loosened screws and stable screws, the average maximal insertional screw torque (MIT) was 9.8 cNm and 39.5 cNm, respectively (p <0.05). Additionally, the length of the stable screws was significantly longer versus the loosened screws (p <0.05). Lower MIT and shorter screw length located near the ends of the lateral mass may predict loosening, which can lead to facet non-union. Sufficient facet decortication with bone packing is one of the important factors contributing to the facet fusion.     

Relationship between Pathological Characteristics and Radiological Findings on Perfusion MR Imaging of Meningioma

Few studies have reviewed the roles of perfusion magnetic resonance (MR) imaging in the histopathological examination of meningiomas. We analyzed the relationships between radiological findings on perfusion MR imaging and pathological characteristics such as origin of the tumor, mitotic activity, pathological subtype, and perifocal edema formation. The subjects were 21 surgical cases of meningioma preoperatively evaluated by perfusion MR imaging. A region of interest (ROI) was set inside of the tumor, and perifocal edema of the same size, cerebral blood volume (CBV), and cerebral blood flow (CBF) on perfusion MR and diffusion-weighted (DW) imaging were analyzed. These radiological data were evaluated in comparison with histopathological characteristics. On perfusion MR imaging, the average ratio of CBV against the contralateral side was 6.43 (1.13–20.0) and that of CBF was 7.73 (1.34–11.3). There was no significant relationship with perfusion MR imaging data, tumor volume, or perifocal edema volume. However, the large peritumoral edema group often had a higher CBV and CBF than the non-large peritumoral edema group. The skull base group had a significantly higher CBV and lower signal intensity on DW images than the non-skull base group. Signal intensity on DW images was higher in grade II or III than in grade I. Perfusion MR imaging data revealed that the higher ratio of peritumoral edema against tumor size was associated with higher blood flow and blood volume under intratumoral circulatory conditions, and that skull base meningioma had a higher blood volume than non-skull base meningioma.     

The Preclinical Safety Evaluation of Human Monoclonal Antibody against Cytomegalovirus

The human monoclonal antibody against cytomegalovinis (Mab C23)was examined pharmacokinetically and toxicologically as partof the preclinical studies prior to approval for human use.Rats given repeated intravenous administrations of Mab C23 producedno antibodies against Mab C23 and maintained a blood Mab C23level in a dose-dependent manner. However, pregnant rabbitsproduced antibodies against Mab C23. The half-life of Mab C23in plasma was 15.9 days in rats, which was similar to that ofnormal human serum -globulin (NHSG). Neither behavioral effectsnor circulatory disturbance was found in mice, rats, and dogseven after a single intravenous injection of 100 or 200 mg/kg,which corresponds to 50 or 100 times the intended clinical dosage.The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasionswith 1- or 2-week intervals elicited a transient decrease inleukocyte counts in rats given 10 or 20 mg/kg, but no adverseeffects in cynomolgus monkeys. Mab C23 did not cause any reproductiveor developmental toxicity when administered to rats and rabbitsat dose levels of 20 mg/kg or less. However, pregnant animalsshowed lower plasma levels of Mab C23 than non-pregnant animals.The chromosomal aberration test disclosed no clastogenicityin human lymphocytes. An immunostaining for Mab C23 revealedno localizations in several tissues of cynomolgus monkeys givenintravenous doses of Mab C23. The preclinical safety evaluationin animals other than rabbits, which produced no antibodiesagainst Mab C23, showed that the behavior of Mab C23 is pharmacokineticallysimilar to that of NHSG and is as safe as NHSG, which has longbeen used as a biological agent. However, because there wasa difference in blood levels of Mab C23 between pregnant andnonpregnant animals, its clinical administration to pregnantpatients should differ from that to non-pregnant patients.     

Update on Intensive Neuromonitoring for Patients with Traumatic Brain Injury: A Review of the Literature and the Current Situation

Intracranial pressure (ICP) measurements are fundamental in the present protocols for intensive care of patients during the acute stage of severe traumatic brain injury. However, the latest report of a large scale randomized clinical trial indicated no association of ICP monitoring with any significant improvement in neurological outcome in severely head injured patients. Aggressive treatment of patients with therapeutic hypothermia during the acute stage of traumatic brain injury also failed to show any significant beneficial effects on clinical outcome. This lack of significant results in clinical trials has limited the therapeutic strategies available for treatment of severe traumatic brain injury. However, combined application of different types of neuromonitoring, including ICP measurement, may have potential benefits for understanding the pathophysiology of damaged brains. The combination of monitoring techniques is expected to increase the precision of the data and aid in prevention of secondary brain damage, as well as assist in determining appropriate time periods for therapeutic interventions. In this study, we have characterized the techniques used to monitor patients during the acute severe traumatic brain injury stage, in order to establish the beneficial effects on outcome observed in clinical studies conducted in the past and to follow up any valuable clues that point to additional strategies for aggressive management of these patients.