A phase I study of combination chemotherapy using TS-1 and pirarubicin (THP) for advanced gastric cancer

The safety of chemotherapy combining TS-1 and pirarubicin (THP) for treatment of recurrent or locally advanced gastric cancer was evaluated. THP was administered by intravenous drip infusion at a dose of 14 mg/m2 every other week. TS-1 was administered orally at a dose of 40 mg/m2 twice a day for 2 weeks followed by 2 weeks of rest (level 1), for 3 weeks followed by 2 weeks of rest (level 2), and for 4 weeks followed by 2 weeks of rest (level 3). Three patients were treated with the level 1 schedule. One patient with peritoneal dissemination received 22 courses of the treatment, and benefited from a long-term NC. However the remaining 2 cases were diagnosed as PD after 4 courses and were withdrawn from further treatment. Two patients in this group suffered from grade 2 adverse events according to the NCI-CTC. Only 1 patient who had liver metastasis was treated at level 2. Fourteen courses were administered, and a PR was achieved while grade 2 adverse events were observed. One of 3 patients who were treated with level 3 had grade 3 adverse events. Consequently, 3 more cases were added to this dose level, and no additional grade 3 adverse events were observed, while grade 2 adverse events were seen in 4 cases. Urinary urgency had completely disappeared in 1 patient with peritoneal recurrence. Myelosuppression, which was the main observed adverse event, was well controlled and of brief duration. The response, including alleviation of clinical symptoms, was confirmed in 3 of 5 chemo-naive patients.     

Link between linear hyperintensity objects in cerebral white matter and hypertensive intracerebral hemorrhage

BACKGROUND: We retrospectively studied the relationship between linear hyperintensity objects (LHOs) on T(2)-weighted magnetic resonance images (MRI) in the cerebral white matter and the occurrence of hypertensive intracerebral hemorrhage (HIH). METHODS: Forty-nine hypertensive patients with a fixed imaging condition MRI were classified into three groups: HIH (n = 17), ischemic stroke due to hypertensive vasculopathy (n = 19), and hypertension only (n = 13). After assessing clinical and radiological background information among these groups and the reliability of LHO measurements, polynomial logistic regression analysis was used to identify the factors relating to HIH. RESULTS: HIH had a significantly higher LHO number (p = 0.002) and larger diameter (p = 0.007). The LHO number showed an excellent interrater (kappa = 0.91, 95% CI = 0.87-0.94, SEM = 6.2%) and intrarater reliability (kappa = 0.95, 95% CI= 0.92-0.97, SEM = 4.8%), and was the most significant independent indicator of HIH (OR = 1.29, 95% CI = 1.05-1.60, p = 0.017). The number of microbleeds was an additional indicator (OR = 3.73, 95% CI = 1.10-12.65, p = 0.034). CONCLUSIONS: LHOs are closely linked to HIH. A prospective, longitudinal study is needed to clarify whether LHOs can predict HIH.     

Tumor targeting based on the effect of enhanced permeability and retention (EPR) and the mechanism of receptor-mediated endocytosis (RME)

This review is focused on the macromolecular drug carrier systems by the effect of enhanced permeability and retention (EPR) and the mechanism of receptor-mediated endocytosis (RME). The effect of EPR is thought to be useful for the targeting of the macromolecular drugs to the tumor tissues on a vasculolymphatic level. The RME reveals the selective recognition, high affinity binding, and immediate internalization for the ligand on a cellular level. In the receptor, recognizing transferrin, a level of expression on the tumor cells is higher than that on the normal cells. We have used serum albumin and transferrin as drug carriers to deliver mitomycin C (MMC) to the tumor tissues and into the tumor cells. The properties of the conjugates of MMC to serum albumin and transferrin were examined in vitro and in vivo. We concluded that MMC could be delivered to the tumor tissue and cells by the use of albumin and transferrin as drug carriers.     

Microsuture-tying forceps with attached scissors for bypass surgery

BACKGROUND: Bypass surgery requires the shortest temporary occlusion time of a recipient artery during anastomosis. For this purpose, we have devised a microforceps with attached scissors that makes it possible to perform the multiple steps involved in anastomosis without exchanging instruments. This microforceps avoids having to exchange instruments twice in one suturing, such as that between a microsuture-tying forceps or a microneedle holder and microscissors in conventional methods. METHODS: The instrument is made of stainless steel and is 15.5 cm long. Using this microforceps with scissors, we can suture, tie, and cut a ligature fluently for consecutive sutures without exchanging instruments. The mean time during one suturing was compared between two patient groups treated by conventional method and with use of this instrument. RESULTS: This instrument was used for 34 patients with ischemic cerebrovascular disease (including three who needed deep-site anastomoses) and allowed us to perform superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses uneventfully. This instrument saved 15.2 s in the mean time during one suturing. CONCLUSIONS: Although it is of paramount importance to practice tying sutures well, this new instrument removes the need to exchange conventional instruments, and we believe it will save time and, therefore, decrease complications during bypass surgery.     

Effect of nedaplatin, 5-FU,and leucovorin combined with radiation therapy in unresectable esophageal carcinoma

A 51-year-old male was assessed as having esophageal squamous cell carcinoma with trachea invasion and cervical lymph node metastasis. After one course of chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU) and Leucovorin (LV), the patient had progressive disease (PD) of the primary lesion and metastatic lymph nodes, and a side effect of severe nausea. One course of nedaplatin, 5-FU and LV combined with radiation was performed alternatively. The effect was evaluated as a partial response (PR) of the primary lesion and metastatic lymph nodes. There were no adverse side effects such as nausea or renal dysfunction except for pancytopenia of grade 2. Increased serum levels of vascular endothelial growth factor (s-VEGF) decreased after the chemoradiotherapy and increased again during continued radiotherapy alone. More information is needed as to whether changes in s-VEGF relate to the clinical effects of the treatment.     

Effective use of combination chemotherapy with paclitaxel and 5-fluorouracil in a case of non-resectable advanced gastric cancer

The patient was a 67-year-old man who had gastric cancer located in the posterior wall of the stomach and who underwent surgery on June 27, 2001. The operative finding was carcinomatous peritonitis in which the primary lesion was considered to be surgically unresectable. Therefore, only a probe laparotomy was performed. Under full informed consent, we performed combination chemotherapy with paclitaxel and 5-fluorouracil, 5-fluorouracil (600 mg/m2/day) was infused continuously for 120-hours (day 1-5) on administration and paclitaxel (60 mg/m2) was infused for 1.5 hours after premedication at day 8, 15 and 22 on an outpatient basis. After 2 courses of the chemotherapy, the tumor markers were reduced remarkably, ascites had completely disappeared, and abdominal lymph nodes had decreased. No serious adverse event was observed and the patient maintained good QOL throughout the treatment.     

Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin

An important clinical problem in the treatment of oral squamous cell carcinoma is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro (Komatsu et al., Cancer Res 60, 1312-1316,2000). However, the clinical significance of this transporter has not previously been addressed. Our aim of this study was to investigate if ATP7B is expressed in oral squamous cell carcinoma and whether its expression correlates with prognosis and reduced responsiveness to cisplatin treatment. Biopsy tissues were obtained from the tumors of 70 patients with oral SCC, and 51 patients received cisplatin-based preoperative chemotherapy. We performed immunohistochemical analysis of ATP7B using monoclonal antibody against ATP7B in 51 oral SCC and adjacent neoplastic tissues. The significance of ATP7B in the prognosis of patients with oral SCC was also examined in the survival analysis of mortality follow-up data covering the period 1991 through 2000. We retrospectively examined the expression of ATP7B in primary oral SCC carcinoma and its association with chemotherapeutic effect. A variable degree of cytoplasmic staining of tumor cells was observed in 54.9% (28/51 cases) of the analyzed carcinomas. Patients with ATP7B-positive tumors had a significantly inferior response to chemotherapy compared with the patients with ATP7B-negative tumors (P = 0.03). The patients who received cisplatin-based chemotherapy with ATP7B-positive carcinomas had a significantly poorer overall survival than those with ATP7B-negative tumors (P = 0.015). These findings suggest that high levels of ATP7B expression in oral SCC are associated with unfavorable clinical outcome in patients with oral SCCs treated with cisplatin-based chemotherapy. ATP7B expression may be a preoperative indicator for a choice of cisplatin in some patients.     

Noninvasive assessment of arterial distensibility in adolescents using the second derivative of photoplethysmogram waveform

To clarify the clinical usefulness of the second derivative of the waveform of the fingertip photoplethysmogram (SDPTG), we examined the relationship between the pattern of the SDPTG waveform and risk factors related to atherosclerosis in 1,495 boys and girls aged 9–17 years. The fingertip photoplethysmogram and its second derivative wave were automatically recorded from the second digit of the right hand with the subjects lying in a supine position. The SDPTG waveform consisted of a, b, c and d waves in systole and an e wave in diastole. The heights of the a and d waves were measured from the baseline, and the ratio of the height of the d wave to that of the a wave (d/a ratio) was calculated. The d/a ratio had a negative correlation with the systolic (SBP) and diastolic blood pressures (DBP), atherogenic index (AI) and immunoreactive insulin concentrations (IRI) after adjustment for age. Multiple linear regression analysis revealed that the d/a ratio was associated more with body height than the risk factors for atherosclerosis in boys and girls at the growth period. The effect of sex- and height-specific cutoff values of the 10th percentile for the d/a ratio was therefore tested. The results showed that subjects with d/a ratios lower than the 10th percentile had significantly higher SBP, DBP, AI and IRI values compared to those with higher d/a ratios. These findings suggest that differences in the length of the vascular system, which are related to increases in body height, may modify the SDPTG waveform pattern during adolescence. When the body height as well as age and sex is adequately allowed for, the d/a ratio may be useful for the evaluation of arterial distensibility and for identification of individuals at an increased risk of developing atherosclerosis. Electronic Publication     

Respiratory control during postural changes in anesthetized cats

The effect of postural changes on respiration was investigated in ten anesthetized cats by applying body tilting during the inspiration phase while recording respiratory patterns, as given by the diaphragmatic EMG, together with either the lung volume or the air flow temperature. The results show that the head-up tilting during inspiration reduced the period of the inspiratory phase and increased the end-inspiratory lung volume. On the other hand, the head-down tilting during inspiration had opposite effects. These effects disappeared after transection of the vagus nerve. However, labyrinthectomy did not diminish the effects, probably because of functional suppression of the vestibular system due to the anesthetic. When correlating the activity of 15 vagal afferents presumably originating from the slowly adapting lung stretch receptors with lung volume changes during tilting, their maximum firing rate (87 +/- 15.7 Hz) was increased with an increase in the lung inflation volume and was attained earlier on head-up tilting and it was reduced with a decrease of the lung volume on head-down tilting (63 +/- 16.6 Hz) as compared with the value in the horizontal position (74 +/- 14.2 Hz). These results suggest that respiratory modulation during head-up or head-down tilting is consistent with the Hering-Breuer reflexes and minimizes the externally induced lung volume changes during postural changes.