Evaluation of the Maruyama Computer Program Accuracy for Preoperative Estimation of Lymph Node Metastases from Gastric Cancer

Controversy still exists about the optimal lymph node (LN) dissection for potentially curable gastric cancer. For rational LN dissection it is important to know the incidence of metastasis at each LN station. For this purpose a computer program was developed using data from 4302 primary gastric cancers treated at the National Cancer Center Hospital in Tokyo between 1969 and 1989. To evaluate the accuracy of the computer program, the differences between the individual reports generated by the computer and the stored data were investigated in 282 Italian patients submitted to curative gastrectomy and D₂ or more extended LN dissections for gastric cancer. Receiver operating characteristic (ROC) analysis was used to assess the sensitivity and specificity of the program for predicting LN metastases in each of the 16 regional LN stations. The computer program showed good predictive ability for LN metastases in most of the 16 LN stations, as the areas under the curve ranged from 0.741 (station 15) to 0.944 (station 8), with a mean of 0.856. A critical cutoff point of 18% of the program's expected percentage was the value maximizing the validity of the prediction. Using an “absolute” cutoff point of 0%, the overall rate of false-negative (FN) predictions in 176 N+ patients was 11.9%; of these, 11 (6.2%) were absolute FNs, in which the program totally failed to estimate LN metastases; the remaining 10 cases (5.7%) were relative FNs because the specific prediction was positive for a different depth of stomach invasion. The low number of D₃/D₄ lymphadenectomies in the historical database may affect the low estimate of metastases to N₃/N₄ nodes generated by the program. Based on these data, the program predicts with good accuracy the extent of LN metastases from gastric cancer, but it is not recommended for directing the surgeon to perform more extensive lymphadenectomy.     

Evaluation of cell proliferation and apoptosis in Helicobacter pylori gastritis using an image analysis processor.

BACKGROUND: Infection of the gastric mucosa by helicobacter pylori is primarily responsible for gastritis, gastric ulcer, adenocarcinoma, and lymphoproliferative disorders. H. pylori appears to accelerate apoptosis and the proliferation of the gastric epithelium directly or indirectly. To precisely assess the proliferative and apoptotic profile of .H pylori-infected gastric mucosa, a quantitative imaging system is now required. METHODS: Fifty-two patients with H. pylori gastritis were the subjects of the study. Biopsy materials were taken from at least two sites (usually three to five sites) including the antrum and corpus. The grade of gastritis was evaluated by the updated Sydney System. The proliferative and apoptotic profile was examined by Ki-67 immunohistochemistry and by a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling method. In addition, Ki-67-positive cells were quantitated by an image processor for analytical pathology (IPAP) system. RESULTS: H. pylori density and polymorphonuclear neutrophil activity were significantly decreased after H. pylori eradication ( P< 0.0001). Chronic inflammation (P< 0.0001) and lymphoid follicle numbers ( P < 0.0005) were also significantly decreased after the eradication. Glandular atrophy and intestinal metaplasia were slightly decreased after eradication, but the decrease did not reach the significant level. the Ki-67 labeling index was significantly decreased after the eradication P< 0.0001). The apoptosis index was also decreased after the eradication, but this decrease did not reach the significant level ( P = 0.06). CONCLUSION: our data suggest that the activation of proliferative cells and induction of apoptosis in the gastric mucosa is a response to H. pylori-induced mucosal damage. Moreover, IPAP may be a useful technology for evaluating the results of immunohistochemistry, and it could provide quantitative and reliable data for studying H. pylori gastritis.     

DIAGNOSIS OF CONGENITAL CYTOMEGALOVIRUS INFECTION BY EXAMINATION OF PLACENTA: Application of Polymerase Chain Reaction and in Situ Hybridization

We examined the placentas of 12 patients in whom congenital cytomegalovirus CMV infection was suspected from serological and or pathological evaluation. Seven patients died including four intrauterine deaths and five survived. On histological examination, the characteristic inclusion bodies were detected in only three placentas, and villitis with plasma cell infiltration was seen in eight placentas. Immunohistochemistry using a specific antibody against CMV improved the sensitivity of CMV detection 10 cases were positive . With the polymerase chain reaction PCR following the extraction of DNA from formaldehyde-fixed placenta samples, CMV DNA was detected in seven cases. All 12 subjects were diagnosed with CMV infection by additional Southern blot analysis after the PCR. CMV DNA was also detected by an in situ hybridization method in all cases. With current molecular biological techniques the placenta can be reliably used for the diagnosis of congenital CMV infection.     

The significance of arytenoid edema following radiotherapy of laryngeal carcinoma with respect to residual and recurrent tumour

We sometimes experience patients with persistent or progressive arytenoid edema, among which residual or recurrent cancer is often accompanied. Because it is difficult to distinguish tumour rest or recurrence from normal tissue sequelae in the early period after irradiation, it is important to know both the contributing factors for arytenoid edema, and the incidence of residual or recurrent tumours in patients with postirradiation laryngeal edema. We therefore reviewed the charts of 67 patients with early laryngeal carcinoma who had received a curative dose of irradiation in the last 5 years. Fourteen patients (20.9%) had moderate or severe laryngeal edema persisting for or developing at more than 3 months after completion of a course of definitive radiotherapy. The incidence was highest in supraglottic T₂ disease, followed by glottic T₂ tumour. Of the 14 patients with edema, six (42.9%) had persistent or recurrent disease. The primary disease was uncontrolled in 18 patients, 17 of whom received successful salvage surgery. In patients without residual tumours, the edema was usually moderate and resolved within a year, although four patients had chronic edema lasting more than a year after treatment. All four had supraglottic T₂ lesions and received 70 Gy of X-ray. We also reviewed, for sake of comparison, the records of 38 patients treated with radiotherapy at doses of more than 40 Gy between l975 and 1980, when endoscopic microsurgery for laryngeal cancer was introduced as a primary part of treatment. The incidence of persistent or late developed edema over the period, though not significant, was 36.8%: nearly twice that of the last 5 years. Microscopic endolaryngeal surgical procedures seem to have been a causal factor for edema in this period.     

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Japanese patients

We conducted molecular analysis of two candidate genes for spinal muscular atrophy (SMA), the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP), in 16 Japanese patients with SMA and compared the phenotypic features of SMA in these patients with the corresponding genotypes. Exons 7 and/or 8 of SMN were homozygously deleted in 11 SMA type I (Werdnig-Hoffmann disease) patients, two SMA type II patients and one SMA type III patient. Exons 5 and 6 of NAIP were homozygously deleted in six SMA type I patients. No patient had a deletion in NAIP without a deletion in SMN. Mechanical ventilation was required during the first 7 months of life in the SMA type I patients who had a deletion in both SMN and NAIP. Ventilatory support was initiated within 2 years after birth in patients who had a deletion in SMN but not in NAIP. We detected homozygous deletion of exon 5 of NAIP in the unaffected mothers of two SMA type I patients. In these families, the patients exhibited a deletion in both SMN and NAIP. The parents and unaffected siblings of these patients did not have a deletion in SMN. The present findings support the hypothesis that SMN deletion plays an important role in the development of SMA and suggest that combined deletion of both SMN and NAIP may be relevant for determining the disease severity.     

Gene Amplification of int-2 and erbβ in Human Esophageal Cancer: Relationship to Clinicopathological Variables

Gene amplification is a relatively frequent event in human malignant tumors and is believed to play an important role in tumor progression. The int-2 and erbB genes are amplified more frequently than any other genes in human esophageal cancer. In order to investigate the correlation between these two proto-oncogenes and the clinical behavior of esophageal cancer, we examined DNA amplification of int-2 and erbB and analyzed their relationship to clinicopathological variables. Genomic DNA was extracted from 21 esophageal squamous carcinomas and normal esopfiageal mucosa, as well as from 4 metastatic tumors. We used Southern blot analysis for detection of gene amplification. Amplification of int-2 was observed in 13 of 21 cases (62%) and in all the metastatic tumors (4/4; 100%). We found a significant correlation between amplification of int-2 and the length of the primary lesion. Amplification of erbB was detected in 3 of 18 patients (17%). All patients who showed amplification of erbB also demonstrated amplification of int-2. These results suggest that amplification of int-2 or neighboring genes on 11q may participate in tumor progression and metastasis in patients with esophageal squamous cancer.     

Incidence of nodal metastasis around the superior border of the pancreas based on number of metastatic perigastric nodes

Received for publication on Jul. 17, 1998; accepted on Oct. 14, 1998     

Significance of a diastolic notch in the uterine artery flow velocity waveform induced by uterine embolisation in the pregnant ewe

Objective To investigate the relation between placental embolisation and the diastolic notch in the uterine artery flow velocity waveform of pregnant ewes under general anaesthesia.
Methods Seven pregnant ewes at a gestation 16 to 17 weeks were anaesthesized and micro beads of gelfoam were injected into the uterine artery; changes in the uterine circulation were assessed by Doppler velocimetry.
Results Gelfoam embolisation reduced uterine blood flow in a dose-dependent manner, from a mean (95% CI) of 568 mL/min (495–641) to 159 mL/min (131–187) after the injection of 30 mg of gelfoam, and increased the uterine vascular resistance from 135 mmHg mine L⁻¹ (103–167) to 498 mmHg mino L⁻¹ (422–574). A diastolic notch in uterine artery flow velocity waveform was observed after 20 mg to 25 mg of gelfoam in two ewes and after injection of 30 mg of gelfoam in all seven animals. Injection of 30 mg of gelfoam increased the pulsatility index to 2–4 (1.9–2.9) from 0.6 (0.5–0.7). The mean uterine vascular resistance at the time of the appearance of a diastolic notch was 414 mmHg mine L⁻¹ (377–451).
Conclusion These findings suggest that an elevated pulsatility index and the presence of a diastolic notch in the uterine artery flow velocity waveform are indicators of increased uterine vascular resistance and impaired uterine circulation.     

Bucolome, a potent binding inhibitor for furosemide, alters the pharmacokinetics and diuretic effect of furosemide: potential for use of bucolome to restore diuretic response in nephrotic syndrome.

To determine whether bucolome (5-n-butyl-1-cyclohexyl-2,4,6-trioxoperhydropyrimidine), a nonsteroidal anti-inflammatory agent, can reverse diuretic resistance of furosemide in patients with nephrotic syndrome, we examined the inhibitory effect of bucolome on the protein binding of furosemide in serum and urine. Bucolome significantly inhibited the protein binding of furosemide not only in serum but also in urine of preparation albumin (UPA), which mimics urinary albumin concentration in patients with nephrotic syndrome by ultrafiltration method. The binding percentage of furosemide to albumin was approximately 70% in UPA. With coadministration of bucolome to healthy volunteers, renal clearance of furosemide was increased, reflecting the increase of the free fraction of furosemide in serum. Furthermore, coadministration of bucolome caused a significant increase of urine volume and sodium concentration in urine. Even at higher urine levels of furosemide, the inhibitory effect of bucolome on the protein binding of furosemide in UPA remains constant, and changes in pH at weakly acidic pH levels (pH 5.5-6.5) did not alter the inhibitory effect of bucolome. Interestingly, coadministration of bucolome with furosemide in doxorubicin (Adriamycin)-induced nephrotic syndrome model rats alleviated the diuretic resistance. These results suggest that bucolome has a potent inhibitory effect on the protein binding of furosemide in the urine and can partially restore the diuretic response of furosemide in patients with nephrotic syndrome by increasing the free fraction of furosemide at the site of action.     

Characterization of antimutagenic mechanism of 3-allyl-5-substituted 2-thiohydantoins against 2-amino-3-methylimidazo[4,5-f]quinoline.

3-Allyl-5-substituted 2-thiohydantoins (ATH-amino acids) derived from allyl isothiocyanate and amino acids can inhibit the mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the Salmonella assay. In this report, we studied possible mechanisms for the inhibition using rat liver S9 in assays for ethoxyresorufin O-deethylase (EROD), a marker activity for cytochrome P450 1A (CYP1A), which activates heterocyclic amines, and the Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). Quantitative analysis of ATH-amino acids and IQ during incubation with rat liver S9 fraction by HPLC showed that ATH-amino acids could act as S9-inhibitors, thereby inhibiting metabolic activation of IQ. Among the tested ATH-amino acids, ATH-Phe, ATH-Trp, ATH-Leu and ATH-Val showed a dose-dependent inhibition of EROD activity. ATH-Gly, ATH-Glu, and ATH-Asp behaved as blocking agents toward N-hydroxy-IQ, but exhibited no inhibition of EROD activity.