A randomized controlled trial comparing a prepackaged low-residue diet with a restricted diet for colonoscopy preparation: the impact on the results of colonoscopy in adenoma detection.

AIM: This study aimed to investigate the clinical utility of a prepackaged low-residue diet (PLD) compared with a restricted diet (RD) for colonoscopic bowel preparation. METHOD: A prospective randomized controlled trial was carried out with patients undergoing colonoscopy. One hundred patients were randomly assigned to PLD and RD groups. In the RD group, the patients received an information sheet containing acceptable low-residue options and instructions from the medical staff. All patients received 10 ml sodium picosulphate the day before colonoscopy and 1 l of polyethylene glycol with ascorbic acid (PEG-A) on the day of the colonoscopy. If the bowel preparation was not adequate, an additional PEG-A solution was given. The primary outcome was the efficacy of colonic cleansing as rated by the Boston Bowel Preparation Scale (BBPS). The additional amount of PEG-A solution, adenoma detection rate and patient tolerance were assessed as secondary outcomes. RESULTS: The BBPS score in the PLD group was 7.3 ± 1.7 compared with 6.5 ± 1.7 in the RD group. The quality of bowel preparation was significantly better in the PLD group (P < 0.05). The mean amount of additional PEG-A solution in the PLD group was smaller than in the RD group (293.8 ± 474.8 vs 444.1 ± 625.0 ml), but there was no statistical difference between the two groups. Adenoma detection rates and patient tolerance were similar in the two groups. CONCLUSION: Prepackaged low-residue diets PLD is superior to RD for bowel preparation for colonoscopy.

Cell-free and concentrated ascites reinfusion therapy (CART) for management of massive malignant ascites in gastric cancer patients with peritoneal metastasis treated with intravenous and intraperitoneal paclitaxel with oral S-1.

BACKGROUND: Massive malignant ascites originating from peritoneal metastasis of gastric cancer is difficult to control and resistant to chemotherapy. Cell-free and Concentrated Ascites Reinfusion Therapy (CART) is one of the types of apheresis therapy, by which filtered and concentrated ascites containing albumin and globulin is reinfused intravenously to patients. We retrospectively studied the feasibility of intraperitoneal (IP) chemotherapy combined with CART in gastric cancer patients with massive malignant ascites. METHODS: Paclitaxel (PTX) was administered via an IP access port implanted in the subcutaneous space. If patient had massive ascites at the start of treatment, paracentesis was performed through a percutaneous IP catheter and then CART was performed. PTX was administered through the catheter until the ascites diminished. RESULTS: A total of 127 CART procedures in 30 patients were analyzed. The average volume of processed ascites was 3.1 L, which was concentrated to 0.33 L containing 85.5 g protein on average. Significant increases in urine volume, serum total protein and albumin level were found after the CART. Increase in body temperature (0.3°C), decrease in platelet count (3.8 × 10(4)/µl), and changes in blood pressure (2 mm Hg) were found after the CART procedure, but no clinically significant adverse event was experienced. The median survival time and 1-year survival of 30 patients who received IP chemotherapy combined with the CART procedure was 10.2 months and 43.3% respectively. CONCLUSIONS: IP chemotherapy combined with CART might be a promising strategy for patients with massive malignant ascites originating from peritoneal metastasis of gastric cancer.

Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis.

BACKGROUND: A phase II study to evaluate the efficacy and tolerability of weekly i.v. and i.p. paclitaxel (PTX) combined with S-1 was carried out in gastric cancer patients with peritoneal metastasis. PATIENTS AND METHODS: Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered i.v. at 50 mg/m(2) and i.p. at 20 mg/m(2) on days 1 and 8. S-1 was administered at 80 mg/m(2)/day for 14 consecutive days, followed by 7 days rest. The primary end point was the 1-year overall survival (OS) rate. Secondary end points were the response rate, efficacy against malignant ascites and safety. RESULTS: Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination, 13 with peritoneal recurrence and six with positive peritoneal cytology only. The median number of courses was 7 (range 1-23). The 1-year OS rate was 78% (95% confidence interval 65% to 90%). The overall response rate was 56% in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The frequent grade 3/4 toxic effects included neutropenia (38%), leukopenia (18%) and anemia (10%). CONCLUSION: Combination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Angleplasty in gastric tube reconstruction after esophagectomy.

Anastomotic leakage after radical esophagectomy is mostly caused by the hypoxia and high tension at the esophagogastric anastomotic site. Here, we introduce a new surgical technique, 'Angleplasty,' to enable the tensionless anastomosis at a highly oxygenic site of gastric conduit. In short, the seromuscular layer is cut for a perpendicular direction against a lesser curvature at a gastric angle and the gastric wall is carefully divided between the muscular and submucosal layers for longitudinal direction for 4-5 cm in length. Then, the wound is closed with seromuscular sutures for longitudinal direction. With this maneuver, the lesser curvature of the gastric roll is significantly elongated and the anastomosis site of the gastric conduit can be moved more distal on the greater curvature of the stomach where it is expected to receive more oxygen supply. This technique takes only several minutes, but provides highly favorable conditions for esophagogastric anastomosis and thus is clinically useful to reduce the risk of anastomotic leakage after esophagectomy.

Imatinib mesylate inhibits proliferation of rheumatoid synovial fibroblast-like cells and phosphorylation of Gab adapter proteins activated by platelet-derived growth factor.

Receptors for platelet-derived growth factor (PDGF) are abundantly expressed on synovial fibroblast-like (SFL) cells from patients with rheumatoid arthritis (RA), and stimulation with PDGF enhances both the anchorage-dependent and -independent growth of RA-SFL cells. To elucidate the molecular mechanisms responsible for the excessive growth of RA-SFL cells and to seek a novel molecular-targeting therapy for RA, we examined the expression of adapter proteins and the effect of the specific inhibition of PDGF receptor activation by imatinib mesylate. Cultured SFL cells were used in the present study after 2-5 passages. The anchorage-dependent and -independent growth patterns of the SFL cells were evaluated using a tetrazolium-based assay and colony formation in 0.3% agar, respectively. Adapter proteins Gab1 and Gab2 were expressed in RA-SFL cells, and both proteins were rapidly (< 1 min) tyrosine-phosphorylated after the stimulation of RA-SFL cells with 10 ng/ml of PDGF and, to a lesser extent, after stimulation with 100 ng/ml of epidermal growth factor (EGF). The inhibition of PDGF receptor tyrosine kinase activation by 1 microM or less of imatinib mesylate specifically suppressed the PDGF-dependent, but not EGF-dependent, tyrosine phosphorylation of various proteins. Moreover, imatinib mesylate abolished both the anchorage-dependent and -independent proliferation of RA-SFL cells induced by PDGF stimulation. These results suggest that Gab adapter proteins are expressed and likely to be involved in the growth signalling of rheumatoid synovial cells and that imatinib mesylate, a key drug in the treatment of chronic myeloid leukaemia, may also be effective for the treatment of RA.

Microsatellite instability of cancers and concomitant adenomas in synchronous multiple colorectal cancer patients.

The precise role of microsatellite instability (MSI) in the development of multiple colorectal cancers has not been elucidated. In the present study, the authors examined MSI and the clinicopathological features of both cancers and concomitant adenomas in nonfamilial multiple synchronous colorectal cancer (multiple CC) patients. Fifty adenomas and 108 cancers were obtained from the surgically resected specimens of 51 multiple CC patients. Nine microsatellite markers were used to determine MSI by polymerase chain reaction (PCR). The frequency of MSI-H adenomas in multiple CC patients was higher than that in single CC patients, while MSI-H frequency of cancers was similar to that in single CC patients. There was a tendency that, in multiple CC patients, when a patient has an MSI-H adenoma, he/she also has MSI-H cancer. The clinicopathological features of multiple CC were similar to those of single CC except the ratio of mucinous cancer and concomitant adenomas. According to this study, in some multiple CC patients, genetic instability seems to play an important role in the development of cancers as well as adenomas. We regard MSI testing for multiple CC patients is useful to distinguish "MSI-related" multiple CC from "MSI-unrelated" multiple CC, and MSI-related multiple CC should be followed up carefully as hereditary nonpolyposis colorectal cancer (HNPCC) patients.

Recent-onset bell palsy complicated by diabetes: comparison of steroid and lipoprostaglandin E(1) therapy.

OBJECTIVE: To compare megadose steroid therapy (n = 17; group S) and lipoprostaglandin E(1) (lipo-PGE(1)) therapy (n = 14; group L) in patients with recent-onset Bell palsy complicated by diabetes. DESIGN: A nonrandomized controlled trial was performed. The 2 groups were almost identical in age, sex distribution, and laterality, and there was no difference in the average palsy scores in the 2 groups either at the time of the first visit or when the palsy was at its worst. RESULTS: There was no statistically significant difference in the cumulative rates of improvement in the 2 groups 4 weeks, 2 months, or 6 months after the first visit, revealing no difference in the therapeutic effects of the 2 agents. During the therapy, fasting blood glucose concentrations were increased in all patients in group S, whereas they were not increased in group L. Complicated diabetes was aggravated in group S, while it was not aggravated in group L. CONCLUSIONS: Lipo-PGE(1) therapy may have improved vascular flow in the facial nerves and accelerated recovery, resulting in a rate of improvement comparable with that obtained through megadose steroid therapy. Lipo-PGE(1) is a useful treatment method for patients with Bell palsy complicated by diabetes.

Microsatellite instability of colorectal cancer and adenoma in synchronous multiple colorectal cancer patients with associated extracolonic malignancies.

We examined microsatellite instability (MSI) in nonfamilial multiple synchronous colorectal cancer (multiple CC) patients. We divided the patients into two groups, those with and without extracolonic primary malignancies, and compared the frequency of MSI between the two groups. A colectomy was performed in 52 multiple CC patients between 1985 and 1998. Of them, 10 patients had extracolonic malignancies, while the other 42 patients did not. The MSI frequency was higher in the patients with extracolonic malignancies than in those without extracolonic malignancies, although it was not statistically significant (40% vs 19%, P = 0.21). Regarding the lesions, MSI frequency of cancers was higher in the multiple CC with extracolonic malignancies than in those without extracolonic malignancies (33% vs 13%, P = 0.033). From our results, there was statistically no difference in the existence of extracolonic malignancies between the patients with at least one MSI-positive cancer and those patients without any MSI-positive cancers. On the other hand, there was a significant correlation between MSI-positivity and the existence of extracolonic malignancies.

Immunohistochemical demonstration of inducible nitric oxide and nuclear factor-kappa B with reference to age-related changes in the mouse spiral and vestibular ganglion.

The morphology and immunohistochemistry of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-kappa B) were studied on the spiral and vestibular ganglion of young and old ddy mice. The significant decrease in the number of the spiral ganglion cells and a significant expression of iNOS and NF-kappa B were observed in old mice. In contrast, in the vestibular ganglion of all animals examined, decrease in the number of the ganglion cells or expression of iNOS and NF-kappa B were not observed. Although the relevance of enzymatic systems for the protection of vestibular ganglion cells in old individuals from harmful oxidative stress increased with aging should be further clarified, lack of harmful stress due to nitric oxide (NO) may be one of the plausible reasons for that the vestibular ganglion cells were not decreased in number with aging, since iNOS was not detected in the vestibular ganglion cells in the animals tested in the present study.

Diagnostic primer sets for microsatellite instability optimized for a minimal amount of damaged DNA from colorectal tissue samples.

BACKGROUND: The diagnosis of microsatellite instability from a minimal amount of highly damaged DNA, extracted from formalin-fixed, paraffin-embedded tissue by the microdissection method, is difficult. Therefore, optimized primer sets were newly designed for substitution of documented ones. METHODS: DNA was extracted from 15 archival colorectal carcinomas and used as templates for polymerase chain reaction. Nine standard microsatellite markers (BAT-25, BAT-26, BAT-40, D18S69, D2S123, D5S346, D10S197, D17S250, and D18S58) were selected for diagnosis of microsatellite instability in colorectal carcinomas. All polymerase chain reaction conditions for primer sets were unified to save experimental time. RESULTS: The primer sets for the latter five markers documented in the literature were redesigned because of poor efficiency for damaged DNA. As a result, the number of DNA samples, sufficiently amplified at all markers, improved from 0% to 93%. CONCLUSIONS: Diagnostic primer sets for microsatellite instability, optimized for a minimal amount of damaged DNA from colorectal tissue samples, were established.

Genetic alterations in ulcerative colitis-associated neoplasia focusing on APC, K-ras gene and microsatellite instability.

The status of genetic alterations in ulcerative colitis (UC)-associated neoplasia (UCAN) was investigated focusing on microsatellite instability (MSI) which is seen in a certain fraction of colorectal carcinomas, and adenomatous polyposis coli (APC) gene and K-ras gene, in which mutations occur in the early stage of sporadic colorectal tumorigenesis. Thirty-one UCAN from 15 UC patients who had undergone colorectal resection at our institution were investigated. There were 8 lesions of invasive carcinoma, 15 high-grade dysplasia (HGD) and 8 low-grade dysplasia (LGD). DNA was extracted from each neoplastic lesion and corresponding non-neoplastic tissue by a microdissection method. MSI status at 9 microsatellite loci, loss of heterozygosity (LOH) at the APC locus, and K-ras codon 12 point mutation were examined. As for MSI, 4/31 (13%) UCAN (carcinoma: 1/8 (13%), HGD: 2/15 (13%), LGD: 1/8 (13%)) were MSI-high (3 or more unstable loci) and 12/31 (39%) UCAN (carcinoma: 3/8 (38%), HGD: 6/15 (40%), LGD: 3/8 (38%)) were MSI-low (1 or 2 unstable loci). LOH at the APC locus was not found in 9 UCAN from 6 informative (heterozygous) cases. The K-ras mutation rate of UCAN was 3/31 (9.7%) (carcinoma: 2/8 (25%), HGD: 1/15 (7%) and LGD: 0/8). MSI is relatively common in UCAN and is present at the early stage of tumorigenesis of UCAN, while the involvement of genetic alterations of the APC gene and K-ras gene is small. MSI may be one of the mechanisms of the increased neoplastic risk in UC, and UCAN may develop through a different carcinogenic pathway from sporadic carcinomas.

[Influencing factors on occurrence and relapse in ulcerative colitis].

The concordance rate of monozygotic twins showed that the occurrence of ulcerative colitis required both internal and environmental conditions. Genetic studies revealed that IBD1 locus on chromosome 16 and IBD2 locus on chromosome 12 showed highly suspicious susceptibility for inflammatory bowel disease. The other possible internal factors include antineutrophil cytoplasmic antibodies and mucin abnormality. Many environmental factors have been reported to cause relapse. These are viral and bacterial infection, medicine such as antibiotics, non-steroidal anti-inflammatory drugs and aminosalicylates, colonic ischemia, post-examination state, psychological stress, winter season, travel and overwork.

An experimental study of intramural blood supply network of the stomach wall.

BACKGROUND/AIMS: A fundamental experiment was undertaken with reference to local resection with lymphadenectomy for gastric cancer. The intramural blood supply network of the stomach wall, about which no reports have previously appeared, was surgically investigated. METHODOLOGY: Five pigs were used. The left gastric and the right gastroepiploic vessels and their branches were removed from all the animals. The right gastric vessels were also removed, while the short gastric and the left gastroepiploic vessels were preserved in the 1st pig. Only the short gastric vessels were preserved in the 2nd, and the right and the short gastric vessels in the 3rd. After resection of the whole stomach with the spleen, angiography was performed through the preserved arteries. The 4th and 5th pigs underwent the same procedures as the 1st, with additional local resection of the stomach in the 5th. Both pigs were maintained for 1 year and then, angiography was performed. RESULTS: When the short gastric and the left gastroepiploic vessels, or the short and the right gastric vessels were preserved, the whole stomach continued to receive blood supply through the intramural network. Stomach wall resection therefore can be performed with no complications after these procedures. CONCLUSIONS: The present results confirm the possibility of local resection with lymphadenectomy as a treatment for gastric cancer.

Three-dimensional helical computed tomography with intravenous cholangiography for sclerosing cholangitis manifested as postcholecystectomy symptom.

A 46-year-old woman who had upper abdominal pain 10 years after cholecystectomy, and who had incidental sclerosing cholangitis (SC), was investigated by three-dimensional helical computed tomographic (3-DHCT) cholangiography with contrast medium, because endoscopic retrograde cholangiography (ERC) was unsuccessful and a second ERC was not permitted by the patient. The cholangiogram demonstrated annular strictures of the bilateral hepatic duct at the confluence of the common hepatic duct, and dilatation of the left intrahepatic biliary duct. Although we could not clarify the cause of the biliary tract deformity at the time of the 3-DHCT, the tentative diagnosis of postcholecystectomy deformity of the biliary tree led to successful treatment by right liver lobectomy and hepaticojejunostomy. Histologic findings were compatible with SC. From this experience and the literature, we suggest that 3-DHCT cholangiography with contrast medium can contribute to the preoperative diagnosis of morphological changes in the biliary tree in patients with postcholecystectomy symptoms.

Effect of aging on the expression of iNOS and cell death in the mouse cochlear spiral ganglion.

The age-related induction of inducible nitric synthase (iNOS) and apoptotic cell death in spiral ganglion cells (SGCs) of ddy strain mice were studied with immunohistochemical method and TdT-mediated dUTP-biotin nick end labeling (TUNEL), respectively. A large amount of iNOS was expressed in SGCs of 18- to 24-month-old mice, but not in those of the mice less than 12 months of age. Moreover, these mice were accompanied by a great rise in auditory brainstem response threshold as well as a great decrease in the number of SGCs that seemed to be due to preceding cell death of the cells. However, we were unable to find apoptotic TUNEL-positive cells in the spiral ganglions. This was assumed to be due to a very short clearance time of the dead cell bodies of less than one hour. As has been known, NO produced by iNOS can implicate in causes for either protection of cells from peroxidation and cell death. In the present study, therefore, the steep augmentation of iNOS in the SGCs of senescent mice implies that the iNOS initially induced to protect SGCs from the cytotoxicity of cellular peroxidation eventually contribute to the cell death of SGCs themselves.

Critical bandwidth determined by masking in the presence of two narrow-band noises.

In this experiment, the critical band (CB)-widths were measured using two narrow-band noises (NBNs) with steep cut-off slopes as a masker, varying their spectral level and center-frequency. The following results were obtained: (i) The CB-widths at all center-frequencies were narrower than the classical CB-widths estimated by Zwicker et al [J Acoust Soc Am 29:548-557 (1957)], and decreased continuously toward the lower frequency at the center-frequencies below 500 Hz, though Zwicker's data were constant in the same range. These results barely coincided with the frequency dependence of the equivalent rectangular bandwidth (ERB) which was estimated from the shape of the auditory filter measured directly. (ii) Level dependence of masking noise in CB was constant beyond 20 dB of the masked threshold. This depends on the use of NBN as a masker. (iii) The CB was influenced by distortion products and off-frequency listening. Accordingly, the bandwidths might differ with the experimental method.

Psychophysical tuning curve and critical band determined by masking in the presence of FM sounds.

Frequency modulation (FM) sounds were used as simultaneous maskers to estimate the psychophysical tuning curve (PTC). Maskers (800 ms duration) were FM sounds sweeping upward (1.2-->2.8 kHz) in Experiment I and downward (2.8-->1.2 kHz) in Experiment II. The signal was a pure tone of 2 kHz and the signal levels were 15-, 20-, 30-, and 35-dB SL. Masked PTCs were obtained as a function of masker frequency. The results were as follows: (i) When an upward-sweeping FM sound is used for high signal level, the slope of the PTC is shallower on the low frequency side and steeper on the high frequency side, and the 10-dB bandwidth of PTC coincides with that of the restricted PTC. (ii) When a downward-sweeping FM sound is used for the high signal level, the above relation for the PTC slope is reversed, and the 10-dB bandwidth for PTC coincides with that of unrestricted PTC. (iii) PTCs determined by masking in the presence of FM sounds apparently restrict the subject to listening to off-frequency, and it is shown that the bandwidth of PTC properly reflects the critical band. (iv) The properties of these PTCs can be easily explained by a neural network model of lateral inhibition, so we can accept a hypothesis that the hierarchical processing mechanism is incorporated within the inferior colliculus for parallel signal processing. (v) We conclude that the frequency resolution and the critical band filtering are, therefore, realized in a psychophysically relevant way in the auditory midbrain level.

Relationship between psychophysical tuning curves and critical bandwidths.

In Experiment I, band noises were used as signals and pure tones were used as maskers. The conventional psychophysical tuning curves (PTCs) present the following characteristics depending on the signal level; slopes of the PTC are steeper than those of the auditory nerve fibers frequency threshold curve (FTC). This result from the large effect of the combination tones and, especially, of the off-frequency listening. Bandwidths of PTC do not depend on both signal levels and duration, but they are narrower than the equivalent rectangular bandwidth (ERB) of auditory filters. Masked thresholds at tips of PTC are affected by the temporal integration of signal sound at signal levels of 10- and 20-dB SL, but are not affected at 30-dB SL. This implies a close relation between PTCs and critical bandwidths (CB-widths). In Experiment II, pure tones were used as signals and band noise were used as maskers. The low- and high-frequency slopes were steeper in Experiment I. The flat parts of the masked threshold at the tips of curves become broader as the signal duration increased. No such flattening was found at a 30-dB signal level, irrespective of signal duration. The results of Experiment II coincide with the prediction derived from the excitation-pattern model. Masked thresholds at the tip of PTC were the same as in Experiment I. The conventional PTC represents the psychological frequency selectivity, and its 3-dB bandwidth corresponds to the CB-width. However, the quantitative properties depend greatly upon the bandwidths of the band noises used as signals or maskers.