An oral anticancer drug, TS-1, enabled a patient with advanced gastric cancer with Virchow's metastasis to receive curative resection

We encountered a patient with advanced gastric cancer, with Virchow's lymph node metastasis, who subsequently underwent curative resection after neoadjuvant chemotherapy with the newly developed oral anticancer drug, TS-1. The patient was a 67-year-old woman who had a type 2 tumor in the middle third of the stomach, and Virchow's lymph node metastasis, which was diagnosed by fine-needle aspiration cytology; she also had swollen paraaortic lymph nodes. Curative resection was considered impossible, and TS-1 (100 mg/day) was administered for 28 days in one course, mainly in the outpatient clinic. Although grade 2 stomatitis interrupted the therapy on day 21 of the second course and on day 7 of the third course, the type 2 tumor showed marked remission (partial response; PR) and the metastasis in the Virchow's and paraaortic lymph nodes had completely disappeared after the third course (complete response; CR). Eleven weeks after the completion of the TS-1 treatment, total gastric resection with D3 lymph node dissection was performed. Histopathological examination revealed tumor involvement only in the mucosal and submucosal layers of the stomach and the no. 4d lymph node. Most of the tumor was replaced with fibrosis with granulomatous change in the muscularis propria of the stomach and in the no. 3, no. 6, and no. 7 lymph nodes. This may be the first report of a patient with advanced gastric cancer with Virchow's lymph node metastasis who successfully received curative resection following neoadjuvant chemotherapy with a single oral anticancer drug. Received: August 7, 2001 / Accepted: January 28, 2002     

Cell cycle arrest and the induction of apoptosis in pancreatic cancer cells exposed to adenosine triphosphate in vitro.

Adenosine triphosphate (ATP) has been shown to be an inhibitory or a stimulatory agent for cell growth in various types of cells. Here, we studied the effects of extracellular ATP on two pancreatic cancer cell lines, PK-1 and YAPC established by us. In both cell lines, ATP inhibited cell growth in a time- and dose-dependent manner, whereas the same doses of ATP stimulated DNA synthesis. Flow cytometric analysis of the cells incubated with or without ATP demonstrated the ATP-induced striking increase in cells at S-phase. The same analysis showed also the increase in sub-G0/G1 population in the same analysis and the electrophoretic pattern of DNA showed the occurrence of ATP-induced cell disintegration likely to be apoptosis. We suggest that extracellular ATP is cytotoxic for pancreatic cancer cells because of its induction of cell cycle arrest at S-phase and cell death, possibly apoptosis, overcoming the promotion of the entry into S-phase.     

Laparoscopic ethanol injection therapy for hepatocellular carcinoma.

Ethanol injection into HCC tumors is an effective therapy and percutaneous ethanol injection therapy (PEIT) is performed on many HCC patients. However, there are cases in which PEIT becomes difficult because the HCC could not be detected by ultrasonography or the tumor is located in an area where it is impossible to perform PEIT. Nine patients with HCC underwent laparoscopic ethanol injection therapy (LEIT) in our institution. Their tumors were located on the liver surface and could be visualized by laparoscopic examination. Ethanol injection was performed under laparoscopic direct visualization. The total injected ethanol volume required ranged from 4 to 15 ml and in most cases both tumor size and alpha-fetoprotein (AFP) levels decreased after LEIT. Three cases showed a transient complication of abdominal pain or/and portal vein damage. Other severe complications were not observed. All cases required additional therapies, including transcatheter arterial chemoembolization (TAE) or PEIT to complete the tumor necrosis. In conclusion, LEIT is a safe and effective therapy for HCC located on the liver surface, but should be combined with other therapies to facilitate its effect against HCC.     

Visual event-related potentials in progressive supranuclear palsy

The purpose of this study is to assess the cognitive function in early stages of progressive supranuclear palsy (PSP). Visual event-related potentials (visual ERPs) were examined in five non-demented patients with PSP and seven control subjects. ERPs were recorded using Figure (non-verbal) and Kanji (verbal) oddball paradigms. The latencies and amplitudes of N100 and P300 components were not significantly different between the PSP and control groups. However, the score of Hasegawa's dementia scale-revised (HDSR) was correlated with P300 amplitudes in the Figure task only in the PSP group. Since the P300 amplitude is related to attentional resources, changes in visual ERP induced by non-verbal stimuli might be associated with the attentional impairment even in early stages of PSP. In the Kanji task but not in the Figure task, the reaction time was prolonged in the PSP group, and positively correlated with the P300 latency in both groups. Visual verbal stimuli might be a good tool to evaluate the information processing in the early stages of PSP. Recording of visual ERP using both non-verbal and verbal stimuli could be helpful to assess a mild cognitive dysfunction in PSP.     

Meiotic instability of the CAG repeats in the SCA6/CACNA1A gene in two Japanese SCA6 families

Intergenerational stability of the CAG repeat number has been considered to be a specific molecular feature of SCA6 compared with other CAG repeat diseases. Nevertheless, we showed meiotic instability of the CAG repeats in the SCA6/CACNL1A gene in two Japanese SCA6 families, including de novo expansion. In one family, the CAG20 allele expanded to the CAG26 one during paternal transmission, and in the other family, the CAG19 allele expanded to the CAG20 one during maternal transmission. Although it is controversial as to whether the CAG20 allele is pathological or not, this is the first case of haplotype analysis-proven de novo expansion in SCA6, confirming the derivation of an expanded allele from one normal allele. We should carefully follow up the individuals carrying the CAG20 allele in our family who show normal neurological and radiological findings at present.     

Hopkins syndrome: oral prednisolone was effective for the paralysis

We describe here a 5-year-old girl who presented flaccid paralysis of the left upper limb after recovery from bronchial asthma. T2-weighted magnetic resonance imaging of the cervical cord revealed a focal high intensity area in the left anterior horn at the C6-C7 level. She was treated with oral prednisolone, and paralysis resolved within two months. Thirty cases of Hopkins syndrome have been reported so far, but its cause remains unknown. Early administration of prednisolone might ameliorate paralysis in this syndrome.     

Detection of stable chromosome aberrations by FISH in A-bomb survivors: comparison with previous solid Giemsa staining data on the same 230 individuals

PURPOSE: To evaluate the relative abilities of the solid Giemsa staining (conventional) and fluorescence in situ hybridization (FISH) methods in the detection of stable chromosome aberrations in the peripheral blood lymphocytes of A-bomb survivors. MATERIALS AND METHODS: Lymphocytes from a total of 230 A-bomb survivors for whom prior chromosome aberration data had been obtained by the conventional method were recently examined afresh using FISH in which chromosomes 1, 2 and 4 were painted with composite probes. RESULTS: It was found that the early use of the solid Giemsa staining method had allowed the detection of translocations with a mean frequency of 73% of the value for the genome-equivalent translocation frequency (F(G)) that was now obtained using FISH. The disparity may at least in part be due to the reciprocal exchange of seemingly identical amount of chromosome material; such exchanges can escape detection by the conventional method but can be readily identified using FISH. CONCLUSION: It has previously been established that the conventional method can detect about 20% of radiation-induced translocations as abnormal monocentric chromosomes. Present results indicate that an additional 50% can be detected if proper karyotyping is conducted and the remaining 30% are not likely to be detected unless FISH or banding methods are used. Thus, solid Giemsa staining accompanied by karyotyping may not be quite as unsuitable as is generally assumed for retrospective biodosimetry analyses, which deal mainly with stable aberrations.     

Evaluation of value of coronary artery bypass grafting without cardiopulmonary bypass for emergency or subemergency case

From August 1999 through September 2000, emergency (operation within 24 hours after hospitalization) or subemergency (within 48 hours) coronary artery bypass grafting without cardiopulmonary bypass (OPCAB) was performed in 16 patients (EM group) with a mean age 71.9 years old (range: 47-85). The patients were divided into 3 groups of which were acute myocardial infarction (AMI) group, chronic heart failure (CHF) group and unstable angina (u-AP) group, and compared preoperative hemodynamics, the number of graft, target arteries, bypass patency and hospitalization period after surgery with 26 patients performed the elective OPCAB in the same duration (EL group). All patients in EM group were used intra-aortic balloon pumping (IABP) assist before operation. In EL group, 16 patients (61.5%) were required IABP (p < 0.05). Ejection fraction and cardiac index in CHF group were significantly lower than those of EL group (47.8 +/- 1.1 vs. 63.3 +/- 2.4, 2.8 +/- 0.2 vs. 1.9 +/- 0.2: p < 0.05). Pulmonary capillary wedge pressure in AMI group and CHF group was significantly higher than that of EL group (16.7 +/- 5.9, 20.8 +/- 5.4 vs. 7.2 +/- 0.8: p < 0.01). There was a significant difference in the mean number of bypass in EM group compared with that of EL group (1.8 +/- 0.2 vs. 2.7 +/- 0.2: p < 0.05). In AMI group and CHF group, the grafting rate to the major vessel in the anterior wall was occupied in more than 70% of all bypasses per patient, however that was less than 50% in EL group. The arterial graft was actively used for revascularization. The hospitalization period in AMI group and CHF group was longer than that in u-AP group and EL group (28.5 +/- 9.8, 38.8 +/- 7.4 vs. 15.7 +/- 1.5, 13.0 +/- 0.7: p < 0.01). There was no difference in bypass patency between EM group and EL group (96.6 vs. 97.2). During the follow-up period, any death and complications were not recognized in both groups. These results suggested that OPCAB would be one of the valuable procedures in the emergent coronary artery bypass grafting.     

The effects of capsaicin cream on prostaglandin-induced allodynia

Although intradermal injection of capsaicin produces acute pain and secondary hyperalgesia, long-term topical application of capsaicin cream has been used as a medication for pain relief in various pain conditions. We previously reported that intrathecal administration of prostaglandin (PG) E(2) and PGF(2alpha) into mice induced touch-evoked pain (allodynia) through capsaicin-sensitive and capsaicin-insensitive afferent fibers, respectively. To clarify the mechanism of an analgesic effect by capsaicin cream, here we applied it to the tail and hind paws of mice and investigated its effects on PGE(2)- and PGF(2alpha)-induced allodynia. Twenty-four-hour pretreatment of mice with 0.025% or 0.05% capsaicin cream markedly alleviated allodynia induced by PGE(2), but not by PGF(2alpha). These results suggest that the topical application of capsaicin cream modulates capsaicin-sensitive afferents and ameliorates allodynia evoked by PGE(2) at the spinal level. IMPLICATIONS: Topical application of capsaicin cream alleviates touch-evoked pain induced by the intrathecal administration of prostaglandin E(2). This study may provide a rationale for the use of capsaicin cream as a therapeutic drug for pain relief.