Pharmacokinetic modulating chemotherapy for rectal carcinoma metastases to the liver and lung--a case report

Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic regimen for advanced colorectal carcinoma, in which high serum 5-FU concentrations are attained through the inhibition of 5-FU degradation by simultaneously administered uracil. A 67-year-old woman, presented with unresectable multiple hepatic and pulmonary metastases following abdominoperineal resection of rectal carcinoma, was successfully treated by the PMC. The patient was initially treated by 600 mg/m2/day of 5-FU infusion, once a week, and subsequently 5-FU doses were increased to 750 mg/m2/day and then to 1,200 mg/m2/day. Hepatic metastases responded at the dose of 750 mg/m2/day and pulmonary metastases responded at the dose of 1,200 mg/m2/day. The patient remains partial response (>21 months). 5-FU serum concentrations were higher at night time and the peak concentration of 5-FU was obtained at 3 a.m. 5-FU Cmax of 600 mg/m2/day, 750 mg/m2/day and 1,200 mg/m2/day were 254, 329, 531 ng/ml, respectively. The experience of this case, together with literature review, suggests that pulmonary metastases are more resistant to 5-FU than hepatic metastases in patients with colorectal carcinoma. The high serum 5-FU concentrations at night suggest the chronomodulating nature of PMC and are effective for metastatic colorectal carcinoma.     

A case of multiple hepatic and peritoneal metastases from colon cancer responding to oral UFT+leucovorin chemotherapy

A 57-year-old woman underwent right hemicolectomy (D3) due to transverse colon cancer with multiple liver and peritoneal metastasis. Administration of oral UFT+Leucovorin was started postoperatively. After 6 months, the multiple liver metastases completely disappeared without any adverse reaction. After 14 months, no other recurrence was found by CT scan. This case suggests the usefulness of oral UFT+Leucovorin for progressive recurrent colorectal cancer as home chemotherapy.     

In vitro drug resistance to imatinib and mutation of ABL gene in childhood Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia

Imatinib, the ABL kinase inhibitor, is used not only for Philadelphia chromosome-positive (Ph + ) chronic myelogenous leukemia, but also for Ph + acute lymphoblastic leukemia (ALL), although resistance to the drug tends to develop in an early stage of the clinical course. We describe a childhood refractory Ph + ALL patient in whom progressive resistance to imatinib was correlated with the appearance of a mutation in the BCR-ABL kinase domain and in vitro drug resistance to imatinib as determined by the methyl-thiazol-tetrazolium (MTT) assay. A missense mutation of T to C (Y253H) of the ABL gene was identified in the resistant clone, suggesting that this mutation may play an etiological role in the rapid loss of drug sensitivity.     

Health-related quality of life and treatment outcomes for men with prostate cancer treated by combined external-beam radiotherapy and hormone therapy

Background Health-related quality of life (HR-QOL) is important when considering the treatment options for prostate cancer.Methods From 1992 to 1998, 57 patients were treated by radiotherapy plus hormone therapy (median age, 79 years; median prostate-specific antigen concentration, 15.0ng/ml; median radiotherapy dosage, 60Gy). General HR-QOL was measured by the European Organization for Research and Treatment of Cancer Prostate Cancer QOL Questionnaire, and a newly developed disease-specific QOL survey was used to assess urinary and bowel functions. QOL was also measured in a control group of patients admitted for prostate biopsy.Results The general HR-QOL scores in the radiation group ranged from 70.0 to 91.3, with sexual problems showing the lowest (i.e., worst) score (38.5). Compared with the control group, the scores in the radiation group were worse for physical function and sexual problems. For disease-specific QOL, the radiation group had worse urinary function than controls, but were more satisfied with their urinary function. There was no difference between the radiation group and controls in satisfaction with bowel function. When the control group was subdivided at into two groups: age 75 years or less, and age over 75 years, the QOL score in the radiation group was the same as that in the subgroup aged over 75 years. In subgroups of the radiation patients, according to survey period, there was no difference between the first and last surveys in longitudinal HR-QOL evaluations. The 5- and 10-year overall survival rates were 67.6% and 41.6%, respectively, and the 5- and 10-year cause-specific survival rates were 97.9% and 94.7%.Conclusion The combination of radiotherapy and hormone therapy has a good outcome and patients do not experience poor HR-QOL, except for sexual problems. Moreover, the disease-specific QOL is good, especially for urinary bother.     

Loss of carcinoembryonic antigen-related cell adhesion molecule 1 expression is an adverse prognostic factor in hepatocellular carcinoma

BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a negative regulator of tumor cell growth, and may function as a tumor suppressor. CEACAM1 expression is down-regulated with increasing histologic grade in a number of malignancies. The authors hypothesized that loss of CEACAM1 expression in hepatocellular carcinoma (HCC) cells may function as an adverse prognostic factor. METHODS: A retrospective analysis was conducted of 139 consecutive patients who underwent resection for HCC, with a median follow-up period of 83 months. Immunohistochemistry of the resected specimens was conducted using a monoclonal anti-CEACAM1 antibody. CEACAM1 expression in HCC was classified into two categories: diffuse expression, characterized by positive staining throughout the tumor specimen, or loss of expression, in which there were distinct areas of negative staining within the tumor specimen. RESULTS: Of the 139 patients, 113 were classified as having tumors with diffuse expression and 26 had loss-of-expression tumors. Loss of CEACAM1 expression was more frequent in tumor specimens with Edmondson-Steiner Grades III or IV (21 of 32 [66%]) than in tumor specimens with Grades I or II (5 of 107 [5%]; P < 0.001) and was always seen in areas with the highest histologic grade. Loss of CEACAM1 expression was significantly associated with large tumor size, multiplicity of the tumor, portal vein invasion, and satellite nodules and affected survival adversely, according to univariate (P < 0.0001) and multivariate analyses (relative risk, 5.737; P < 0.001). CONCLUSIONS: Loss of CEACAM1 expression reflects aggressive tumor biology and thus indicates a poor prognosis for patients with HCC.     

Diagnostic Peritoneal Lavage for Diagnosing Blunt Hollow Visceral Injury: The Accuracy of Two Different Criteria and Their Combination

Purpose To test the usefulness of diagnostic peritoneal lavage (DPL) for identifying blunt hollow visceral injury with two different sets of criteria or a combination of the two. Methods Fifty victims with physical examinations and/or computed tomography findings equivocal for blunt hollow visceral injury underwent DPL. Whether or not to perform surgery was determined based on Otomo's DPL criteria [lavage white blood cell counts (L-WBC) over lavage red blood cell counts (L-RBC) divided by 150 (L-WBC ≥ L-RBC/150) in the presence of hemoperitoneum, or L-WBC over 500/mm³ (L-WBC ≥ 500) in the absence of hemoperitoneum]. The cell count ratio, a comparison of L-WBC, L-RBC, peripheral WBC (P-WBC), and peripheral RBC (P-RBC) [(L-WBC/L-RBC)/(P-WBC/P-RBC) ≥ 1] were all calculated retrospectively. Results There were one and two false-positive cases based on Otomo's criteria and the cell count ratio, respectively, with corresponding accuracies of 97.8% and 95.7%, respectively. There were no false-positive or -negative cases according to the combined use of Otomo's criteria and cell count ratio, yielding an accuracy of 100%. Conclusion Although each criterion alone is very accurate in predicting the presence of blunt hollow visceral injury, the combined use of the two would further improve the accuracy of the diagnosis and thereby reduce the number of unnecessary celiotomies.     

Gastrectomy Performed with Noninvasive Positive Pressure Ventilation for a Patient with Severe Chronic Obstructive Pulmonary Disease: Report of a Case

We report the case of a patient with severe chronic obstructive pulmonary disease (COPD) for whom gastrectomy was successfully performed with the use of noninvasive positive pressure ventilation (NPPV). A 63-year-old man who had been suffering from chronic pulmonary emphysema for 12 years and receiving home oxygen therapy (HOT) for 9 years was diagnosed with gastric carcinoma. The patient required supplemental oxygen via nasal cannulae even at rest, and had labored breathing through pursed lips after a short conversation. The forced expiratory volume in 1 s was 400 ml. He underwent conventional gastrectomy under general anesthesia, and was extubated 90 min after surgery and given NPPV support. He was successfully weaned from NPPV on postoperative day (POD) 10 and discharged from our hospital on POD 28. Noninvasive positive pressure ventilation is useful for the perioperative management of patients with severe COPD and for extending the possibilities of surgery for patients on HOT.