Search

Phase lag entropy, an electro-encephalography-based hypnotic depth indicator, calculates diversity in temporal patterns of phase relationship. We compared the performance of phase lag entropy with the bispectral index™ in 30 patients scheduled for elective surgery. We initiated a target-controlled infusion of propofol using the Schnider model, and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation scale every 30 s with each stepwise increase in the effect-site propofol concentration. Phase lag entropy and bispectral index values were recorded. The correlation coefficient and prediction probability between phase lag entropy or bispectral index and the sedation level or effect-site propofol concentration were analysed. We calculated baseline variabilities of phase lag entropy and bispectral index. In addition, we applied a non-linear mixed-effects model to obtain the pharmacodynamic relationships among the effect-site propofol concentration, phase lag entropy or bispectral index and sedation level. As sedation increased, phase lag entropy and bispectral index both decreased. The prediction probability values of phase lag entropy and bispectral index for sedation levels were 0.697 and 0.700 (p = 0.261) and for the effect-site concentration of propofol were 0.646 and 0.630 (p = 0.091), respectively. Baseline variability in phase lag entropy and bispectral index was 3.3 and 5.7, respectively. The predicted propofol concentrations, using the Schnider pharmacokinetic model, producing a 50% probability of moderate and deep sedation were 1.96 and 3.01 μg.ml-1 , respectively. Phase lag entropy was found to be useful as a hypnotic depth indicator in patients receiving propofol sedation.

Immunoscore can effectively predict prognosis in patients with colon cancer; however, its clinical application is limited. We modified the Immunoscore and created a tumor immune microenvironment (TIM) classification system for gastric carcinoma. Unlike previous studies that used small sample sizes or focused on particular immune-cell subtypes, our simplified system enables pathologists to classify gastric carcinomas intuitively using HE-stained sections.Samples from 326 patients with advanced gastric carcinoma were reviewed and analyzed by pathologists using simple determination and digital image analysis. Comprehensive results of cancer-panel sequencing, Epstein-Barr‒virus (EBV) status, and PD-L1, HER2, ATM, PTEN, MET, FGFR2, and EGFR immunohistochemistry were evaluated with respect to the TIM class.The TIM was classified as "hot" (n = 22), "immunosuppressed" (n = 178), "excluded" (n = 83), or "cold" (n = 43). TIM category was significantly associated with numbers of frameshift mutations (P 0.001) and high tumor mutational burden (P 0.004), and predicted overall survival. It was also significantly associated with age, histological type, degree of fibrosis, PD-L1 expression, loss of ATM and PTEN expression (P 0.001), sex, EBV positivity, and HER2 overexpression (P 0.04). "Hot" tumors were frequent in PD-L1 expressing and EBV-positive samples, and in those with ATM and PTEN loss. "Excluded" tumors were frequent in HER2-positive cases, whereas "cold" tumors were more frequent in younger patients with poorly cohesive histology and high fibrosis levels.TIM classification system for gastric carcinoma has prognostic significance and results in classes that are associated with molecular characteristics.

Background Programmed death-ligand 1 (PD-L1) expression has been suggested as a potential predictive biomarker of response to anti-PD-1/PD-L1 therapy. In this study, we investigated whether the expression of PD-L1 in tumour cells is affected by neoadjuvant concurrent chemoradiotherapy (CCRT) or chemotherapy in oesophageal squamous cell carcinoma. Patients and methods Between 2004 and 2014, we collected the medical records of locally advanced oesophageal cancer patients consecutively diagnosed and treated with neoadjuvant CCRT or chemotherapy, followed by curative resection. PD-L1 expression in acquired tissue specimens was evaluated by immunohistochemistry using the H-score. The changes in PD-L1 expression between paired samples were evaluated and we also analysed PD-L1 expression in surgical tumour specimens to evaluate its prognostic role. Results Twenty-eight paired tumour tissues that were acquired before and after neoadjuvant therapy were available: 19 patients with CCRT and 9 with chemotherapy before complete oesophagectomy. The PD-L1 H-score increased significantly from baseline tumour tissues to surgical tumour tissues after neoadjuvant CCRT ( P = 0.007, median H-score from 28 to 52), whereas it decreased significantly after neoadjuvant chemotherapy ( P = 0.048, median H-score from 53 to 22). In a total of 73 patients, including 45 additional cases for the prognosis analysis, patients with higher PD-L1 H-scores (≥20) had poorer overall survival (median 16.7 versus 32.9 months, P = 0.02) than those with lower H-scores ( Conclusions PD-L1 expression in tumour cells increased in oesophageal cancer patients who received neoadjuvant CCRT. Further studies with more cases are necessary to validate these findings.

A*02:687 showed one nucleotide difference with A*02:01:01:01 resulting in an amino acid change.

Molecular targets are emerging rapidly and the development of clinical tests that simultaneously screen for multiple targets has become especially important. We assessed the gene expression levels of three known targets in advanced gastric cancer, epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and N-methyl-N-nitrosoguanidine human osteosarcoma transforming gene (MET), using the nCounter® assay (NanoString Technologies, Seattle, WA, USA) and compared these results with protein overexpression, detected by immunohistochemistry, to evaluate the performance of this new technology. We investigated 42 formalin-fixed, paraffin-embedded tumor samples from patients with gastric cancer. A NanoString-based assay containing a 522 kinase gene panel was investigated. We analyzed the correlations between immunohistochemical findings and kinase gene expression levels of EGFR, HER2 and MET to validate this assay. EGFR, HER2, and MET overexpression were observed in 7 (16.6 %), 5 (11.9 %), and 3 (7.1 %) cases, respectively. For EGFR, HER2, and MET, the concordance rates between the NanoString-based assay results and the immunohistochemistry methods were 83.3, 97.6, and 100 %, respectively. Relative to immunohistochemistry findings, the NanoString-based assay sensitivities and specificities were 85.7 and 82.8 % for EGFR, 100 and 97.2 % for HER2, and 100 and 100 % for MET, respectively. We found a high concordance between immunohistochemistry- and nCounter-based assessments of EGFR, HER2, and MET in advanced gastric cancer. Judged against immunohistochemistry results, the NanoString assay had high sensitivities and high specificities. These results suggest that the nCounter assay provides a reliable, high-throughput assay to simultaneously screen for the overexpression of several target proteins.

Cytomegalovirus (CMV) gastrointestinal (GI) disease has been noticed frequently in cancer patients, causing abdominal pain, diarrhea, and GI bleeding. However, little is known about its actual incidence, clinical presentation, and the risk factors for its development among cancer patients. To answer these questions, we analyzed all cases that occurred during an 18-year period at our center. A case-control study was performed to identify risk factors for CMV GI disease. Electronic medical records were reviewed from individuals who were admitted and diagnosed with CMV GI disease during the period of January 1995 through March 2013 at a tertiary care center. Two CMV disease-free cancer patients were matched as controls. A total of 98 episodes of CMV GI disease were included in this study, and the overall incidence rate was 52.5 per 100,000 cancer patients, with an increasing trend throughout the study period. According to multivariate analysis, male sex, low body mass index, lymphopenia, hematological malignancy, and steroid use and red blood cell transfusion within 1 month prior to the CMV disease were identified to be independent risk factors. Among these factors, RBC transfusion showed the highest odds ratio (OR = 5.09). Male sex, low body mass index, lymphopenia, hematological malignancy, steroid use, and red blood cell transfusion within 1 month prior to the CMV disease diagnosis were independent risk factors for the development of CMV GI disease in adult patients with cancer.

Background: Heat shock protein 90 (HSP90) possesses two major isoforms – HSP90α and HSP90β. They have essential roles in the protection against stressful conditions. They are also important for the re-establishment of cellular homeostasis. We investigated the clinical significance of HSP90α and HSP90β expression in patients with gastric cancer (GC). Methods: HSP90α and HSP90β expression levels were examined immunohistochemically in surgical specimens obtained from 186 GC patients. The correlations between their expression levels and clinicopathological parameters including patient survival were analyzed. Results: The frequencies of larger tumor size (maximum diameter ≥4 cm) and more prominent tumor invasion (≥pT3) in the high intensity HSP90α expression group were 73.4% and 68.8% higher, respectively, than those in the low intensity group (both P = 0.001). High HSP90α expression level was also significantly associated with lymphatic invasion, lymph node metastasis, and advanced stage (TNM stage ≥III) disease (P = 0.047, P = 0.046, and P = 0.004, respectively). Patients with high HSP90α expression levels demonstrated significantly worse survival than those with low HSP90α expression levels (P = 0.047). In contrast, survival did not differ significantly according to the intensity of HSP90β expression. Conclusions: Our results showed that HSP90α overexpression might be associated with disease progression and poorer survival in patients with GC. Therefore, HSP90α could be used as possible biomarker for the prognosis of GC.

Background Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. Methods In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. Findings Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6.5 years; IQR 2.8-12.9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30,000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30,000 copies per mL (NNRTI-higher). Median follow-up was 5.0 years (IQR 4.2-6.0) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3.16 log(10) copies per mL for protease inhibitors versus -3.31 log(10) copies per mL for NNRTIs (difference -0.15 log(10) copies per mL, 95% CI -0.41 to 0.11; p=0.26), and -3.26 log(10) copies per mL for switching at the low versus -3.20 log(10) copies per mL for switching at the higher threshold (difference 0.06 log(10) copies per mL, 95% CI -0.20 to 0.32; p=0.56). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. Interpretation Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. Funding Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT).

The new allele A*33:102 showed two nucleotide differences with A*33:03:01 in exon 3.

This study was designed to investigate the genotypes of human papillomavirus (HPV) in Korean women who had abnormal cervical cytology and to evaluate the clinical accuracy of HPV DNA chip analysis for the diagnosis of cervical neoplasia. Liquid-based cytology preparations, HPV DNA chip analysis, and cervical biopsy were performed in 2358 women. High-risk HPV was identified in 23.5% of 1650 histologically confirmed normal samples (including cervicitis and squamous metaplasia) and in 81.8% of 708 samples with cervical intraepithelial neoplasia (CIN) and carcinoma (P< 0.01). The major prevalent high-risk HPV genotypes in 381 samples of CIN II/III were HPV-16, -58, -33, and -31, in order of prevalence rate (average overall, 78.0%), and HPV-16, -18, -58, and -33 (average overall, 81.2%) in 133 samples of squamous cell carcinoma (SCC). The infection rate of HPV-16 was significantly higher than that of other high-risk HPV genotypes in all normal, CIN, and SCC cases (P< 0.01) and increased with more advanced squamous cervical lesions (P< 0.01). The detection accuracy of high-risk HPV using HPV DNA chip analysis for CIN II or worse was as follows: sensitivity 84% (81–87%), specificity 72% (70–74%), positive predictive value 47% (44–50%), and negative predictive value 94% (92–95%). These results suggest that HPV DNA chip analysis may be a reliable diagnostic tool for the detection of cervical neoplasia and that there are geographic differences in the distribution of high-risk HPV genotypes.

Although perioperative hypothermia is a well-known consequence of general anesthesia, it has been hypothesized that laparoscopic surgery exacerbates hypothermia to a greater extent than open surgery. The aim of this study was to demonstrate that laparoscopic surgery does not represent an increased risk for hypothermia.A case-controlled retrospective study was conducted on 45 patients, 25 undergoing laparoscopic cholecystectomy and 20 undergoing parathyroid surgery under endotracheal general anesthesia. Data were collected regarding age, sex, weight, height, American Society of Anesthesiologists (ASA) status, length of surgery, and anesthesia. In addition, we analyzed the type of intraoperative intravenous fluids, anesthetics and perioperative drugs, and temperature, blood pressure, and heart rate recordings during anesthesia.There was no significant difference between the two groups with respect to age, sex, body mass index (BMI), ASA status, type or amount of intravenous fluids infused, length of anesthesia or surgery, changes in mean blood pressure, or heart rate. Core body temperatures in both groups decreased significantly over time (p 0.05). There was no difference between the groups in terms of maximum drop in temperature (lowest temperature recorded vs baseline temperature) (1.1 +/- 0.7 vs 1.0 +/- 0.7 degrees C, p0.05).This study demonstrates that patients who undergo laparoscopic and open procedures of similar duration under endotracheal general anesthesia have similar profiles in terms of perioperative hypothermia.

OBJECTIVES—The most common neurological manifestations in Wilson's disease are parkinsonism and dystonia. These are assumed to be due to striatal injury, which has been repeatedly demonstrated by pathology and CT or MRI. The substantia nigra has not been shown to be damaged in pathological studies. However, there have been clinical and imaging studies suggesting presynaptic nigrostriatal injury. (1r)-2β-carbomethoxy-3β-(4-iodophenyl)tropane (β-CIT) is a specific ligand that binds to the dopamine transporter (DAT), and can examine the integrity of dopaminergic nerve terminals. Evidence for presynaptic nigrostriatal dopaminergic damage in Wilson's disease was searched for using [123I]-β-CIT SPECT. METHODS—Six patients with Wilson's disease were studied, together with 15 healthy normal controls, and six patients with Parkinson's disease. After injection of [123I]-β-CIT, SPECT studies were done at 18 hours. Specific striatal/occipital binding ratio (S/O ratio) was calculated as (striatal binding−occipital binding)/occipital binding. RESULTS—The specific S/O ratios were 6.22 (1.32) (mean (SD)) in normal volunteers, 3.78 (0.65) in Parkinson's disease, and 3.60 (0.49) in Wilson's disease. CONCLUSION—There was severe loss of the DAT in the striatum suggesting significant damage in presynaptic nigrostriatal dopaminergic nerve terminals. Therefore, a presynaptic lesion may contribute to neurological manifestations in Wilson's disease.

Tuberculosis is still an important cause of granulomatous colitis in developing countries. If we can diagnose tuberculosis using endoscopic biopsy material, clinicians can avoid invasive diagnostic procedures and needless operations. For this purpose, we evaluated clinical manifestations, pathological findings, and diagnostic methods in endoscopically biopsied intestinal tuberculosis patients.From January 1991 to December 1996, 42 patients with intestinal tuberculosis were endoscopically examined and tissue culture, immunohistochemical stain, Ziehl-Neelsen stain, and polymerase chain reaction in fresh and fixed tissue were applied. The pathological findings were analyzed and compared with the results of the other diagnostic methods.In tuberculosis patients, transverse ulcers with surrounding hypertrophic mucosa and multiple erosions were usual colonoscopic findings. The granulomas were found in 74% of the cases. The positivity ranged from 30-45%. There were no significant differences in the positivity among those diagnostic methods (p0.05). The positivity of Ziehl-Neelsen stain in fixed tissue was higher in the group having granulomas and it was reversed in PCR (p0.05). The increasing number of biopsy particles raised the positivity of Ziehl-Neelsen stain and PCR in fixed tissue (p0.05).Transverse ulcers were the most characteristic colonoscopic finding and granulomas were frequent pathological findings in intestinal tuberculosis. Higher positivity and reliable results were found in tissue culture, Ziehl-Neelsen stain, and polymerase chain reaction. To increase the diagnostic rate, the endoscopist should take enough tissue and deep biopsy material from ulcer bases and diseased mucosae.

Background Laparoscopic and robotic gastrectomy have been adopted rapidly despite lack of evidence concerning technical safety and controversy regarding additional benefits. This study aimed to compare clinically relevant complications after open, laparoscopic and robotic gastrectomy. Methods This was a retrospective analysis of prospectively collected data on surgical complications in patients undergoing gastrectomy with curative intent for histologically proven adenocarcinoma between 2005 and 2010 at the Department of Surgery, Yonsei University College of Medicine in Seoul, Korea. Complications were categorized into wound infection, bleeding, anastomotic leak, obstruction, fluid collection and other. Results In a total of 5839 patients (4542 open, 861 laparoscopic and 436 robotic gastrectomies), overall complication, reoperation and mortality rates were 10·5, 1·0 and 0·4 per cent respectively. There were no significant differences between the three groups. Ileus (P = 0·001) and intra-abdominal fluid collections (P = 0·013) were commoner after conventional open surgery. However, tumour stage was higher and more complex resections were performed in the open group. Anastomotic leak, the leading cause of death, occurred more often after a minimally invasive approach (P = 0·017). Conclusion Laparoscopic and robotic gastrectomy had overall complication and mortality rates similar to those of open surgery, but anastomotic leaks were more common with the minimally invasive techniques.

Hyalinizing trabecular tumours (HTTs) are rare follicular-derived neoplasms that behave in an almost benign manner. HTT is frequently misdiagnosed as papillary carcinoma by fine needle aspiration (FNA) cytology or as papillary or medullary carcinoma on surgical resection.The authors examined FNA material from seven cases of histologically verified HTT. Cytological findings were reviewed and correlated with ultrasonographic and histological features. In addition, MIB-1 and calcitonin immunostaining was performed on surgical specimens, and BRAF mutation analysis on three pre-operative FNA specimens and seven histology specimens.The original cytological diagnosis was either suspicious or positive for papillary carcinoma in all patients. The FNA-based differential diagnoses included HTT, papillary carcinoma or, less likely, medullary carcinoma in two patients. Aspirates showed oval to spindle-shaped cells with frequent intranuclear inclusions, isolated in loosely cohesive groups with a trabecular or syncytial pattern in a bloody background. Radiating arrangements of tumour cells surrounding hyaline stroma with serrated calcifications and a lack of papillary or sheet-like fragments may suggest HTT on FNA. Spherical calcified bodies and possible psammoma bodies were frequently found in three cases. Retrospectively, six of the seven cases showed membranous immunoreactivity for MIB-1, but none of the seven possessed the BRAF (V600E) mutation or showed calcitonin reactivity.Although the recognition of HTT on FNA cytology is difficult, because of its morphological similarities to papillary and medullary carcinoma, its characteristic cytological features along with ultrasonographic findings may suggest the diagnosis preoperatively and avoid surgical over-treatment.

To evaluate knowledge about the foreskin and circumcision, and to understand the attitudes of parents to circumcision in Korea, where circumcision in childhood is widely practised with no particular religious or medical background.A nationwide study involving questionnaires was conducted on 5500 parents with at least one son attending elementary school. Responses were obtained from one of the parents.The response rate was 76.1% (4183); circumcision was most common in boys when aged 11 years, followed by neonatal circumcision. Of the parents, 91.3% believed that circumcision is necessary, while 2.1% believed it to be unnecessary. The principal reasons given for circumcision were 'to improve penile hygiene' (82.4%), followed by 'to improve future sexual potency' (7.5%). Among those who did not believe circumcision to be necessary, the most common reason was the expectation of spontaneous retraction of the prepuce with age (55.1%). Most (88.4%) of the parents believed that smegma is not a clean material, and is infected by microorganisms. Most parents (80.6%) thought that circumcision would prevent genital tract infection of the future spouse. Peer pressure was one of the most influential factors in deciding upon circumcision; 41.9% of the parents were anxious that their child might be ridiculed by his peer group unless he was circumcised, while 27.4% of the parents believed that their child might be ridiculed if he was circumcised. Mothers were more positive about circumcision than fathers (P0.05). Parents with a higher education and higher socio-economic status were also more positive about circumcision (P0.05). Mothers were prone to emphasize improved sexual potency (P0.05). There was no significant difference in response between urban and rural areas.This study indicates that common beliefs held by parents about the prepuce or circumcision differ significantly from current medical knowledge, and these beliefs have a major influence on the practice of circumcision in Korea. More clinical research on the natural history of the foreskin is needed, and it is critical that both children and parents are informed about the potential benefits and disadvantages of circumcision.

Microsatellite alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) are observed in most (70% to 80%) gastric carcinomas. To determine whether the microsatellite genotypes are correlated with clinicopathological features, 118 patients with gastric carcinomas were examined by using polymorphic microsatellite markers for LOH on 5 gastric cancer-associated chromosome arms and non-polymorphic BAT markers for MSI. Microsatellite genotypes were categorized as high-frequency MSI (MSI-H), high-level LOH (LOH-H), low-level LOH (LOH-L) and LOH non-detectable (LOH-N). A significant fraction of the MSI-H, LOH-H and LOH-L types was observed in intestinal-type gastric carcinomas, whereas the LOH-N type was highly associated with diffuse-type tumors (p = 0.00162). There was a close relationship between microsatellite genotype and TNM (tumor-node-metastasis) stage (p = 0. 001). Univariate analysis showed that patients of LOH-H or LOH-N types and those of MSI-H or LOH-L types correlated with poor and favorable survival, respectively, not only in all tumor stages (p = 0.0001) but also in stages II and III (p = 0.0271). It is likely that the major genotypes of gastric carcinomas can be placed into at least 4 microsatellite categories, thus allowing the construction of a comprehensive genetic classification useful for the prediction of diverse clinical courses.

We report the imaging findings in a case of pedunculated exogastric leiomyoblastoma presenting as a wandering abdominal mass. Ultrasound and computed tomography showed a large, mixed solid and cystic mass in the peritoneal cavity. Computed tomography clearly showed that the mass was connected to the stomach by a narrow stalk. Small bowel follow-through showed subtle extrinsic indentation of the gastric body. The mass wandered from the right to the left side of the peritoneal cavity during various radiologic examinations.

To determine whether the paracrine secretion of interleukin (IL)-12 can efficiently convert immune responses characterized by high levels of synthesis of IL-4 and immunoglobulin E (IgE) into T helper 1 (Th1)-dominated responses, 3T3 fibroblasts were stably transfected to secrete IL-12 (480 units/10(6) cells/48 hr). Their effects on the T helper cell-mediated immune response were investigated in ovalbumin (OVA)-primed mice. Free mouse recombinant IL-12 was included as a control group. IL-12-secreting fibroblasts (3T3/IL-12) were more effective than free recombinant IL-12 at increasing OVA-specific interferon-gamma (IFN-gamma) production and decreasing OVA-specific IL-4 production in CD4+ T cells. In addition, injection with 3T3/IL-12 cells significantly increased anti-OVA immunoglobulin G2a (IgG2a) levels and decreased anti-OVA IgE levels in OVA-primed mice. This work suggests that IL-12-secreting fibroblasts can efficiently induce an antigen-specific Th1 response and may be beneficial in the treatment of diseases caused by undesirable T helper 2 (Th2)-dominated responses, including allergic diseases.

Interleukin-2 (IL-2) and granulocyte-macrophage-colony stimulating factor (GM-CSF) are cytokines with nonoverlapping pleiotropic effects. In a prior Phase Ib study, this combination of agents exhibited antitumor effects in the lungs of four of eight patients with renal cell carcinoma and pulmonary metastases. We conducted this Phase Ib/II trial to determine the response rate of renal cell carcinoma patients with pulmonary metastases treated with continuous infusion IL-2 plus GM-CSF.Patients with renal cell carcinoma and pulmonary metastases were treated with 1.5, 2.25, or 4.5 x 10(6) IU/m(2)/day 96-hour continuous infusion IL-2 on Days 1-4, 8-11, and 15-18, and 1.25, 2.25, or 2.5 microg/kg/day GM-CSF on Days 8-19.Sixteen patients were treated per protocol, 14 of whom could be evaluated for disease progression. None of these 14 patients had50% shrinkage of either total tumor burden or pulmonary metastasis. One patient developed Grade 5 neurotoxicity. Autopsy revealed acute multifocal cerebral venous thrombosis as well as acute subdural and subarachnoid hemorrhage.The combination of IL-2 and GM-CSF may be associated with marked morbidity and, as in one case in this study, mortality. No significant antitumor activity was appreciated. Thus, the combination of IL-2 and GM-CSF, when administered at this dose and according to this schedule, does not appear to be active in renal cell carcinoma and is associated with significant toxicities. Further studies using this combination of agents should only be undertaken with extreme caution and particular attention to neurotoxicity.

Recently, neoadjuvant chemotherapy (CT) and radiation therapy (RT) have been advocated as a standard treatment for laryngeal preservation in patients with locally advanced laryngeal cancer. However, it is still being debated whether adding neoadjuvant CT to conventional RT makes an effective contribution to laryngeal preservation. The current study was designed to resolve this controversy.Retrospective clinical study.The Severance Hospital, Yonsei Cancer Center, Yonsei University, Seoul, Korea.Eighty patients (stages III, IV) with squamous cell carcinoma of the larynx were divided into two groups according to treatment modalities, which consisted of RT alone (N = 40, Group 1) and neoadjuvant CT plus RT (N = 40, Group 2). Comparative analysis was undertaken to investigate the differences in the organ preservation rate and treatment results between the two groups.There was no significant difference in the response rate and patterns of treatment failure between the two groups. The 5-year survival rate was similar between Group 1 (24%) and Group 2 (31%) (p = .1556). In addition, the larynx was almost equally preserved in Group 1 (62%) versus Group 2 (63%).Radiation therapy without neoadjuvant CT seems to be a valid alternative treatment for the purpose of laryngeal preservation in locally advanced laryngeal cancer.

Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are biologic agents with antitumor activity observed in preclinical models. Some studies of patients with advanced non-small cell lung cancer treated with IL-2 report relatively long survival, despite low response rates. Seventy-six evaluable patients with stage IV non-small cell lung cancer were treated in a randomized Phase II study with either IL-2 alone or IL-2 plus beta-IFN. Patients received either IL-2 at 6 x 10(6) Cetus units/m2 3 days weekly or the combination of IL-2 at 5 x 10(6) Cetus units/m2 plus beta-IFN at 6 x 10(6) units/m2, both given 3 days weekly. Both biologic agents were administered by intravenous bolus injection on an outpatient basis. Objective responses were observed in 3/76 (4%)) patients. Grade 4 toxicity occurred in 3/39 patients treated with IL-2 alone, and in 4/37 patients treated with IL-2 plus beta-IFN. An additional lethal respiratory toxicity occurred in a patient who received IL-2 plus beta-IFN. The median survival of all patients treated on this study was 33 weeks. Despite producing only a 4% objective response rate. IL-2 appears to have a favorable impact on survival comparable to chemotherapy. The role for this immune therapy in the management of non-small cell lung cancer requires further study.

To investigate the underlying contractile mechanism of the sustained tonic contraction (SuTC) induced by repetitive carbachol application in rat detrusor muscles.Longitudinal muscle strips with no mucosa were obtained from the anterior wall of the urinary bladder in 12-week-old Sprague-Dawley rats. Carbachol (5 micromol/L) was applied repetitively to induce SuTC. The carbachol-induced SuTC was assessed in the presence of various Ca2+-channel blockers and drugs affecting intracellular Ca2+ concentration.The first application of carbachol elicited a large phasic contraction followed by a tonic contraction (TC); the carbachol-induced contraction was completely reversed by washing out the solution. However, the initial phasic contraction was not reproduced after a second or further application of carbachol. There was consistently only a SuTC with no phasic contraction. The amplitude of the SuTC was 85% of the TC induced by the first carbachol application. The application of atropine (1 micromol/L) to the bath completely blocked SuTC. The carbachol-induced SuTC was insensitive to nicardipine (5 micromol/L) and extracellular polyvalent cations (1 mmol/L, La3+, Co2+, Cd2+, Ni2+ ). Moreover, a similar SuTC was induced even after the complete elimination of extracellular Ca2+ by adding 2 mmol/L EGTA to the Ca2+-free Tyrode solution. To exclude intracellular Ca2+ sources related to the sarcoplasmic reticulum (SR), the effects of SR Ca2+ pump inhibitors, cyclopiazonic acid (CPA, 10 micromol/L) and thapsigargin (0.5 micromol/L) were tested. The carbachol-induced SuTC was insensitive to pretreatment with CPA and/or thapsigargin. To deplete the ryanodine-sensitive Ca2+ pool, muscle strips were repetitively stimulated with caffeine (10 mmol/L) in the presence of 10 micromol/L ryanodine, which did not affect the carbachol-induced SuTC.Although the characteristics of the carbachol-induced SuTC have not been defined, these results show that a significant proportion of the carbachol-induced contraction in rats is contributed by the SuTC, which is present even in the complete absence of external Ca2+. The SuTC was not affected by limiting the contributions of internal Ca2+ sources. This suggests that the SuTC in rat bladders is unrelated to known Ca2+ mobilization mechanisms.

Adenoma malignum (AM) is known to be one of the malignant tumors that is commonly associated with Peutz-Jeghers syndrome. Recently, the genetic locus of Peutz-Jeghers syndrome was mapped to the telomeric region of chromosome 19p. We analyzed nine sporadic cases of AM with high-density loss of heterozygosity to study the region of chromosome 19p13.2-13.3 using eight microsatellite markers. Our deletion mapping data revealed a distinct region with 100% loss of heterozygosity frequency at marker D19S216. This result indicates that a putative tumor suppressor gene for AM is located at D19S216 on chromosomal band 19p13.3 and plays an important role in AM tumorigenesis.

This study of elderly in-patient subjects' expected level of care given by family members and nurses is intended to provide foundational information for use by nurses in attending to elderly patients. The objects of the study were elderly in-patients over the age of 65 hospitalized at two General hospitals in Chonju; 102 subjects filled out the 60 question survey between December 16 and 24, 1996. The analysis process was conducted using SPSS producing percentage, mean and standard deviation, maximum and minimum values, t-test, ANOVA, and so on. The results are as follows: 1. From the general results of the survey, one can observe that statistically significant differences appeared in various levels of education of the subjects: no education(2.98), primary school completed(2.91), middle school or higher completed(2.77). As shown, the lower level of education correlates with higher care-giving expectation. 2. On a scale of 1(minimum) to 4(maximum), the mean levels of care expected by elderly in-patients from their families is 2.93, with a standard deviation of 0.28. The level of psychological care expected(mean 3.02, standard deviation 0.31) is higher than the level of care expected(mean 2.83, standard deviation 0.34). 3. The level of care expected among those of different levels of dependency for daily living (differentiated as dependent, partially dependent, independent) was highest among the partially dependent(mean 2.98, standard deviation 0.17), but the results were not statistically significant. 4. Elderly in-patients with high levels of emotive interaction with their families expected relatively high levels of physical care, while the highest levels of socio-psychological care were expected from those who reported normal levels of emotive interaction with their families. However, We can see that low levels of care are expected from those reporting low levels of emotive interaction with their families. Overall, the differences in the level of care expected between those reporting different levels of emotive interaction with their families was not shown to be statistically significant.

The best therapy for persons with acute myelogenous leukemia (AML) in 2nd remission is unknown. Bone marrow transplants from an HLA-identical sibling are reported to be better than chemotherapy but this is controversial. The objective of the study was to compare 3-year leukemia-free survival (LFS) in comparable subjects receiving chemotherapy or a transplant. 485 persons with AML in 2nd remission were studied. The chemotherapy cohort included 244 persons treated on trials of the British Medical Research Council, Eastern Cooperative Oncology Group and MD Anderson Hospital. The transplant cohort included 257 persons transplanted worldwide and reported to the international Bone Marrow Transplant Registry (16 were also chemotherapy subjects.) Subjects were selected for comparable age and year of treatment. Preliminary analyses identified two factors correlated with LFS: ageor = or30 years and 1st remission durationor = or1 year; subsequent analyses were partitioned accordingly. Three-year probabilities of treatment-related mortality with chemotherapy and transplants were 7% (95% confidence interval, 3-15%) vs 56% (49-63%). Three-year leukemia relapse probabilities were 81% (74-86%) vs 41% (33-49%). Three-year probabilities of LFS were 17% (12-23%) vs 26 (20-32%). Cohort analysis showed significantly higher LFS with transplants vs chemotherapy in personsor = 30 years and 1st remissions1 year (41% (29-53%) vs 17% (7-32%); P = 0.017) and those in30 years with 1st remissionsor = 1 year (18% (9-29%) vs 7% (2-16%); P = 0.046). Others had comparable LFS with both treatments. These data indicate better LFS with HLA-identical sibling transplants than chemotherapy in some persons with AML in 2nd remission.

Calcification is common in human placentas and is widely recognized as a normal part of maturation and aging of this organ. Eleven human placentas were studied by light and electron microscopy to elucidate the mechanism of placental calcification. Earliest mineral deposits were seen along the trophoblastic basement membrane of the chorionic villi undergoing fibrinoid degeneration. Transmission electron microscopic examination revealed crystalline deposits within small membrane-bound vesicles; the latter appear to be derived from degenerating cells and were particularly numerous within the basement membrane. X-ray microanalysis of these deposits revealed calcium and phosphorus peaks and the pattern of calcium hydroxyapatite was noted by electron diffraction. This pattern of calcification, i.e., precipitation of calcium hydroxyapatite in association with extracellular membrane bound vesicles, is similar to that seen in physiologic and pathologic calcifications of other tissues.

Aging changes of aortic valves are thought to underlie the mechanism of calcification, which leads to calcific aortic stenosis in humans. The study of calcification in the aging valvular connective tissue has been hindered by the lack of a suitable animal model. In search of the model, canine aortic valves demonstrated age changes including calcification remarkably similar to those in humans. The mechanism of calcification was studied in the aortic valves of aged Beagles by electron microscopy. Fibroblasts in the canine aortic valves showed the most prominent age changes. The cells accumulated numerous residual bodies and appeared to disintegrate. The resultant membranous cellular degradation products which sequestered in the extracellular space were the nidi of calcification. It appeared that the membrane of cell debris played an important role in calcification. Canine aortic valve is an ideal model for the study of calcification in relation to aging of the valvular connective tissue.