Acta Medica Okayama 64巻 1号

We examined the feasibility of triplet chemotherapy using cisplatin, docetaxel, and irinotecan for patients with recurrent or refractory non-small cell lung cancer (NSCLC), retrospectively. Twenty-five patients (21 men and 4 women) with NSCLC and good performance status who were <70 years old were analyzed. The median age was 58 years. Most patients had performance status 1 (16/25), stage IV disease (18/25) and adenocarcinoma-histology (16/25). Cisplatin and docetaxel were given on day 1 and irinotecan on day 2;the cycle was repeated every 3 weeks. The objective response rate was 39.1% (95% confidence interval:18.7-59.5%). The median survival time and actual 2-, 3-, and 5-year survival rates were 14.3 months, 32%, 20%, and 8%, respectively. Of note, only 6 patients were treated with gefitinib at the recurrence after triplet chemotherapy;of these, 4 (67%) achieved a partial response, which might result in favorable survival. Grade 3/4 toxicities consisted of neutropenia (100%), neutropenic fever (56%), nausea/vomiting (40%), and diarrhea (16%);no cases of treatment-related death occurred. Triplet chemotherapy showed impressive survival data in our clinical trial, but proved too toxic for use in treating patients with NSCLC in the clinical practice.

Among the 3 mitogen-activated protein kinases -- ERK, p38 MAPK and JNK -- JNK has been suggested to participate in apoptosis, whereas p38 MAPK is thought to be part of the differentiation response. There are many common inducers of JNK and p38 MAPK, but the mechanisms underlying the differential response to apoptosis and differentiation are poorly understood. We found that heatshock activated p38 MAPK at 3min after exposure to a temperature of 44 in stress-hypersensitive PC12m3 mutant cells, while it activated JNK at 20min after the same heat treatment. However, heat shock activated p38 MAPK 5min after heat treatment and JNK 10min after heat treatment in PC12 parental cells. The extent of phosphorylation of p38 MAPK induced by heat shock in PC12m3 cells was significantly greater than that in PC12 parental cells, and a high level of heat-shock-induced neurite outgrowth was observed only in PC12m3 cells. On the other hand, heat-shock-induced JNK activation appeared more quickly and apoptosis started earlier in PC12 parental cells. These findings indicate that short stress induces p38 MAPK and longer stress induces JNK, and that the response of these kinases to heat shock differs depending on cell type.

A 67-year-old woman with debilitation and massive ascites was admitted to our hospital and diagnosed with stage IV scirrhous gastric cancer with peritoneal dissemination. After successful nasojejunal tube feeding because of oral intake disability, TS-1 combined with paclitaxel chemotherapy was selected. TS-1 at 80mg/m2 was given daily via nasojejunal tube for 2 weeks, followed by a 1-week rest, and paclitaxel at 50mg/m2 was administered intravenously on day 1 and 8. There were no serious side effects. After 4 cycles, a partial response was observed and percutaneous transesophageal gastro-tubing (PTEG) was placed. After the fifth cycle, she was transferred to her home and received chemotherapy in an outpatient clinic. After 7 cycles, the disease progressed, and TS-1 combined with low-dose cisplatin was administered for 3 cycles. However, the patient died 16 weeks after discharge. PTEG was useful not only for a route of TS-1 administration, but also for receiving chemotherapy at home to maintain her quality.

In 2000, chlamydial strains OK133 and OK135 were isolated from 2 female patients with cervicitis. These strains were unresponsive to commercially available PCR and LCR test kits for the diagnosis of Chlamydia trachomatis infection, and their phenotypic characteristics were very similar. The OK135 nucleotide sequence in MOMP-VD2 gene closely resembled that of Chlamydophila caviae GPIC. A similar strain was isolated in 2003 from a male patient OKM2 with urethritis, from which the strain SC10-6 was cloned by the plaque purification method. The nucleotide sequence of the entire MOMP gene of SC10-6 was exactly the same as that of OK135. Thus, the strains OK135 and SC10-6, together with OK133, have been called C. caviae-like Chlamydia. We designed primers for nested PCR assay, the product of which showed a single-band 311-bp fragment, to detect C. caviae-like Chlamydia. Of swab specimens obtained from 202 patients from 2003 to 2006 (119 male and 83 female patients), 18 specimens (8.9%) from 14 male and 4 female patients were positive, suggesting that C. caviae-like Chlamydia infection is rather common. Thus far, it has not been determined whether C. caviae-like Chlamydia is pathogenic for humans.

We investigated changes in drug disposition and toxicities with CPT-11 in 15 dialysis patients with gastrointestinal cancers to clarify whether CPT-11 could be administered safely in such patients. For comparison, the same parameters were also investigated in 10 cancer patients not undergoing dialysis. Items investigated included (1) plasma concentrations of SN-38, SN-38G and CPT-11 at 0, 1, 12, 24, 36, 48 and 72h after administration, together with a comparison of mean AUC values for 3 dose levels of CPT-11 (50, 60 and 70mg/m2) in dialysis patients and controls;and (2) occurrence of adverse events. Several findings emerged from this study:(1) No significant difference was observed in the AUC for SN-38 or CPT-11 between the dialysis and control groups;(2) The AUC for SN-38G at each dose was significantly higher in dialysis patients;and (3) Grade 1-4 leucopenia was observed in 11 of the dialysis patients. One patient developed grade 4 leucopenia and died due to sepsis. Anorexia, diarrhea, nausea, alopecia and interstitial pneumonia occurred in 6 dialysis patients. We found changes in drug dispositions of CPT-11, SN-38 and SN-38G in dialysis patients, suggesting that hepatic excretion, especially that of SN-38G, was increased. No significant difference in occurrence of adverse events was observed between the 2 groups. This indicates that CPT-11 can be administered safely in patients on dialysis.

Poorly differentiated adenocarcinoma without papilla or tubule formation of the extrahepatic bile duct is rare. Here we present a case (a 42-year-old Japanese woman) without either pancreatobiliary maljunction or liver disease. The patient had obstructive jaundice. Imaging studies revealed a bile duct tumor obstructing the common bile duct and invading the surrounding tissues. Pathologic examination revealed a dense periductal growth of poorly differentiated adenocarcinoma containing signet-ring cells, but without papilla or tubule formation in the extrahepatic bile duct. The tumor cells directly invaded the pancreatic parenchyma and the portal vein. In the extrahepatic bile duct, poorly differentiated adenocarcinoma may be established as a distinct clinicopathologic entity if the tumors are characterized by:1) the absence of papilla or tubule formation, 2) Asian preponderance, 3) occurrence at a younger age than is usual for patients with biliary cancers, and 4) an aggressive mural invasiveness.

The skeletal muscle is classified into 2 types, slow oxidative or fast glycolytic muscle. For further characterization, we investigated the capillary architecture in slow and fast muscles. The rat soleus and extensor digitorum longus (EDL) muscles were used as representatives of slow and fast muscles, respectively. To investigate capillary density, sections of both types of muscle were stained with alkaline phosphatase;the soleus muscle showed more intense reactivity, indicating that it had a denser capillary structure than the EDL muscle. We then injected fluorescent contrast medium into samples of both muscle types for light and confocal-laser microscopic evaluation. The capillary density and capillary-to-fiber ratio were significantly higher, and the course of the capillaries was more tortuous, in the soleus muscle than in the EDL muscle. Capillary coursed more tortuously in the soleus than in the EDL muscle. Succinate dehydrogenase (SDH) activity, an indicator of mitochondrial oxidative capacity, and vascular endothelial growth factor (VEGF) expression were also significantly higher in the soleus muscle. Thus, we conclude that slow oxidative muscle possess a rich capillary structure to provide demanded oxygen, and VEGF might be involved in the formation and/or maintenance of this highly capillarized architecture.

We report a case of bilateral iliopsoas hematomas that occurred during postoperative therapy after coronary artery bypass grafting (CABG). An 81-year-old woman receiving anticoagulant and antiplatelet therapies under sedation after CABG developed sudden anemia and went into shock. Abdominal ultrasonography showed a right retroperitoneal hematoma. She improved gradually with conservative treatment. Many patients with an iliopsoas hematoma complain of low-abdominal pain or femoral neuropathy, but such local signs may be absent under sedation. In anticoagulant and antiplatelet therapies under sedation, when the cause of anemia and shock is not clear, we should suspect peritoneal hematoma and examine the peritoneal space.

In Liaoning Province in northeastern China, we found a G6PD-deficient patient at the age of 3. By the classification of the World Health Organization, this patient was categorized as class I (very severe G6PD deficiency). When we investigated the G6PD gene of the patient, we found that he had a replacement of G to A at nucleotide 1339. As a result, the amino acid at position 447 should change from Gly to Arg. This replacement is known as G6PD Santiago de Cuba, because it was first discovered in a Cuban boy who showed heavy chronic anemia. Today, 28 G6PD variants have been reported in the Chinese population, and all are categorized as class II (severe deficiency) or class III (mild deficiency);in class II or III deficiency, anemia is not present in daily life, but hemolytic attack can occur when the carrier ingests certain oxidative medicines or foods. This is the first report of a G6PD-deficient Chinese patient in the category of class I. We intended to find other G6PD-deficient cases in northeastern China and tested several hundred blood samples, but no cases of G6PD deficiency were found (0/414). In central China, where falciparum malaria was endemic from the 1950s to 1970s, we found two G6PD-deficient cases (2/27) and the other members from their families whose variant type was G6PD Kaiping (1388GT), which is a common variant in the Chinese population.

The aim of this study was to clarify the factors influencing the dietary behavior of patients with diabetic nephropathy. One hundred twenty-two patients with type 2 diabetes were recruited from the outpatients of Okayama University Hospital in Okayama, Japan. We performed a cross-sectional study using a questionnaire including 206 items among 18 categories as follows:background factors, coping behavior (coping scale), degree of uncertainty in illness (uncertainty scale), and dietary behavior. The data were analyzed by correlation analysis, t-test, one-way analysis of variance, Pearson correlation analysis, and multiple regression analysis. We found that those patients with microalbuminuria alone tended to recognize more mild about their kidney status than those with macroalbuminuria and chronic renal failure. We also found that common factors influencing the dietary behavior of diabetic patients with and without nephropathy are as follows:1. coping with the problem (beta0.342, p0.01);2. anxiety about prognosis (beta0.344, p0.01);3. sex (beta0.234, p0.05);4. uncertainty regarding treatment (beta0.377, p0.01);5. negative coping (beta0.354, p0.01);and 6. employment status (beta0.367, p0.01). Coping and uncertainty in illness had a significant relation to positive support and lack of support. To maintain appropriate dietary behavior in diabetic patients, medical staff need to determine what the social supports are important for the patient, and also to ensure good communication among healthcare personnel as well as positive support for patients and families.