Management of the system to allow the terminal cancer patients and their families to choose from in-hospital care, outpatient care and home care at Matsuyama Bethel hospital

Hospice ward at Matsuyama Bethel Hospital opened in April 2000. The hospice care has been provided for inpatients and outpatients. We considered a system that should be established to allow patients and their families to choose from in-hospital care, outpatient care and home care. The hospice consultation for outpatients opened in April 2004. The terminal cancer patients who are within 6 months of remaining days were hospitalized to the hospice ward. After making the hospice consultation for outpatients, hospice care services have been provided for terminal cancer patients including those with more than 6 months of remaining days under the coordination of palliative care for outpatients and inpatients.     

A terminal phase patient who can return home because of a multi-professional conference--considerations for multi-professional conference

Palliative care has been provided in our sub-acute hospital ward and multi professional conferences have also taken place in order to enhance care. In this paper, we present a 72-year-old female who has suffered from relapse of lung cancer and was able to return home because of an execution of multi-professional conferences. We also present considerations that were carried out in multi-professional conferences. We found some of the important factors for carrying an efficient conference are advance preparations in ahead, punctuality of the conference, a conference place that is kept in the ward, coping with nurse calls and participation of nutritionists. A timely conference, sharing information among the team and the education about a dying process are some of the future subjects.     

Gene testing of hereditary cancer on comprehensive gene medical examination support system

It has been estimated that genetic factors or a combination of genetic and environmental factors play a role in the development of 10-15% of all cancers. A genetic cause of hereditary cancer has been identified in more than 40 diseases till now. For preventing this cancer, gene testing is essential because it has no definite clinical marker as in hereditary non-polyposis colorectal cancer: HNPCC. Much more experience must be accumulated in this testing at the clinical base in order to increase specificity and sensitivity while safeguarding ethical, legal and social issues (ELSI). Recently, the Personal Information Protection Law was enforced. Gene inspection involving hereditary cancer should be carried out under a comprehensive gene medical examination organization. It is important for the family doctor, medical specialist, and gene inspection person in charge to cooperate closely with one another, and this will be a subject of future study.     

Quantitative real-time RT-PCR analysis of NY-ESO-1 and LAGE-1a mRNA expression in normal tissues and tumors, and correlation of the protein expression with the mRNA copy number

We investigated NY-ESO-1 and LAGE-1a mRNA expression in normal tissues and various types of cancer by quantitative real-time RT-PCR. In addition to their high expression in the testis, we observed a low expression of NY-ESO-1 mRNA in the placenta, pancreas and liver, and no expression in 12 other normal tissues. We also observed a low expression of LAGE-1a mRNA in the placenta and ovary, and marginal expression in 13 other normal tissues. In contrast to the previous finding that NY-ESO-1 and LAGE-1a mRNAs were mostly co-expressed in solid tumors, we found an independent expression of NY-ESO-1 and LAGE-1a mRNAs. NY-ESO-1 mRNA expression was mostly associated with LAGE-1a mRNA expression in esophageal and liver cancers, but not in prostate cancer. Immunohistochemistry (IHC) using NY-ESO-1-specific ES121 mAb showed that NY-ESO-1 protein was detected in 6 of 9 and 3 of 10 NY-ESO-1 mRNA-positive specimens from esophageal and liver cancers, respectively. NY-ESO-1 protein expression was correlated with the copy numbers of NY-ESO-1 mRNA. IHC was also performed using ES121 mAb and B9.8 mAb recognizing both NY-ESO-1 and LAGE-1a in 4 esophageal and 6 liver cancer specimens preferentially expressing LAGE-1a mRNA. B9.8-specific staining was observed weakly and focally in one liver cancer specimen expressing >10(5) copies of LAGE-1a mRNA.     

Thymidine phosphorylase expression and efficacy of adjuvant doxifluridine in advanced colorectal cancer patients

To clarify the correlation between the expression level of thymidine phosphorylase (TP) and efficacy of doxifluridine (5'-DFUR) and 5-fluorouracil (5-FU), samples from 177 colorectal cancer patients who underwent curative resection were evaluated by immunohistochemical staining using a newly developed monoclonal antibody 1C6-203. Patients were randomly given either oral 5'-DFUR or 5-FU as postoperative adjuvant chemotherapy. In Dukes' C staged colon cancer patients treated with 5'-DFUR, better survival was observed in the high TP patients than the low TP patients (P=0.025 by the log-rank test). The observed 5-year survival rates were 91.2 and 74.8%, respectively. No correlation between TP expression and patient prognosis was detected in the 5-FU group. In Dukes' C stage colon patients with high TP expression, the 5'-DFUR group had slightly better survival than the 5-FU group. These findings suggest that TP may be a chemosensitive marker for 5'-DFUR as postoperative adjuvant chemotherapy for advanced colon cancer patients.     

Loss of p21WAF1/CIP1 expression in invasive fronts of oral tongue squamous cell carcinomas is correlated with tumor progression and poor prognosis

The clinicopathological significance of cell-cycle proteins has remained unclear in oral tongue squamous cell carcinomas (OTSCC). In the current study, we evaluated several cell-cycle proteins in relation to clinicopathological parameters and disease outcome for OTSCC. A total of 123 previously untreated patients with OTSCC, who underwent surgical treatment, were enrolled. Tumor specimens were examined for expression of p21, p27, p16, p53, and p63 using immunohistochemistry, with reference to clinicopathological factors and disease outcome. It is noteworthy that differences in p21 immunoreactivity were evident between the shallow region and invasive front of tumors within the same specimens. Loss of p21 expression in invasive fronts was found to be associated with clinicopathological factors of tumor progression and poor prognosis. p21 expression in invasive fronts is a significant indicator for impact on survival. Moreover, p21 is one of the important factors that regulate the progression of malignant cells in OTSCC.     

Reduced radiosensitivity and increased CD40 expression in cyclophosphamide-resistant subclones established from human cervical squamous cell carcinoma cells

To investigate the interaction between anticancer drug resistance and radioresistance in cervical cancer cells, 3 single cell-derived cyclophosphamide-resistant subclones were established from the drug- and radiosensitive human cervical squamous cell carcinoma cell line ME180 by chronic exposure cultures with 4-hydroxy-cyclophosphamide followed by limiting dilution. The established cyclophosphamide-resistant subclones were also radio- and multidrug-resistant to 7 other anticancer drugs. Flow cytometric analysis revealed significantly increased levels of CD40 expression on the 3 resistant subclones, whereas no CD40 expression was found on the parent ME180 cells. However, there were no changes in the expression levels of CD29, CD49a-CD49f or CD59 between the parent cells and resistant subclones. A recombinant human soluble CD40 ligand had no effect on the proliferation of the resistant subclones. Irradiation had no effect on the 4-hydroxy-cyclophosphamide sensitivity of the parent cells. These results indicate that the established cyclophosphamide-resistant subclones have impaired cell death signals, which are common to both drug- and radiation-induced apoptosis, and cyclophosphamide may not be an adequate drug for use in concurrent chemoradiotherapy. Furthermore, CD40 activation signals may be associated with the multidrug- and radioresistance in these cyclophosphamide-resistant subclones.     

Cellular kinetics and K-ras codon 12 mutations according to histomorphometric type of colorectal polyps with epithelial serrated proliferation

Recent studies have examined cellular kinetics and genetic abnormalities in colorectal polyps with epithelial serrated proliferation (CP-ESP), including hyperplastic polyps, serrated adenomas, and tubulovillous adenomas. However, difficulty in histologically classifying these lesions and the lack of clear-cut diagnostic criteria have led to inconsistent findings. Some 60 cases of CP-ESP and 6 cases of CP-ESP with malignant transformation were studied. When nuclear size progressively decreased from the bottom and middle layers to the surface layer of the crypts, maturation gradient was considered positive. CP-ESP and CP-ESP adjacent to carcinoma were morphologically classified as being positive or negative for maturation gradient and inferior and lateral glandular branching. Cellular kinetics were evaluated using Ki-67 immunostaining, and polymerase chain reaction (PCR)-dependent preferential homoduplex formation assay was performed to detect the presence or absence of K-ras codon 12-point mutations. CP-ESPs were morphologically classified into five types. In CP-ESP of types 1 to 4, the proliferation zone was confined to the bottom layer of the crypts or extended from the bottom to middle layers. In contrast, the proliferation zone extended throughout the crypts in most type 5 lesions. K-ras codon 12 mutations were detected in only types 3 and 5 CP-ESP. The five histomorphologic types of CP-ESP have distinct patterns of cellular kinetics. Histomorphologically, type 3 CP-ESP is considered an atypical hyperplastic polyp, occasionally associated with an elongated proliferation zone or K-ras mutations. Preliminary evidence indicates some relation between K-ras mutations and structural atypia associated with lateral branching of the crypts.