Faecal lactoferrin is a useful biomarker for mucosal healing in patients with ulcerative colitis during granulocyte and monocyte adsorptive apheresis therapy.

AIM: The study investigated the value of faecal lactoferrin as a follow-up biomarker for mucosal healing of ulcerative colitis during granulocyte and monocyte adsorptive apheresis (GMA) therapy. METHOD: Patients with ulcerative colitis exhibiting a moderate or severe disease activity with a partial Mayo Score (pMS) of over 4 were enrolled in this study. The patients received 10 courses of GMA therapy. The pMS value and faecal lactoferrin level were monitored and compared with the findings of endoscopy until 12 months after the last dose of GMA therapy. RESULTS: Twenty patients (male:female 11:9) were enrolled in this study. Twelve had total colitis, while six had left-sided involvement and two had distal proctitis. Thirteen (65.0%) responded to GMA therapy. The faecal lactoferrin levels were significantly decreased in patients who responded to GMA therapy (P < 0.05), whereas the levels did not change in non-responders. Moreover, the faecal lactoferrin levels correlated with the endoscopic findings (r = 0.792, P < 0.01) and pMS scores (r = 0.529, P < 0.01). The correlation coefficients between the faecal lactoferrin levels and mucosal findings were higher than those observed between the pMS score and mucosal findings. CONCLUSION: The faecal lactoferrin level is a useful biomarker of the mucosal findings in ulcerative colitis. Although endoscopy is the gold standard, the faecal lactoferrin level can be used as a biomarker during GMA therapy in patients with ulcerative colitis.

Gastrointestinal symptoms in idiopathic pulmonary fibrosis patients treated with pirfenidone and herbal medicine.

Pirfenidone is an antifibrotic agent for patients with pulmonary fibrosis, but this drug has adverse gastrointestinal (GI) effects. The first aim of this study was to assess GI symptoms due to pirfenidone by using a new questionnaire for reflux symptoms and dismotility symptoms. Whether adding herbal medicine of rikkunshi-to improved GI symptoms due to pirfenidone therapy was also investigated. This was a randomized controlled trial performed on 17 IPF patients. The patients were assigned to two groups, and the study period was 8 weeks. The pirfenidone group received pirfenidone therapy for 8 weeks with add-on rikkunshi-to from 4 weeks, while the control group did not receive either of these agents. To assess the effects of RK, plasma levels of acyl-ghrelin and des-acyl-ghrelin, serum KL-6 and surfactant protein-D, and pulmonary function tests were monitored. GI symptoms were most severe during the initial 2 weeks of pirfenidone therapy at a dose of 600 mg/day. Both reflux symptoms and dismotility symptoms deteriorated. Rikkunshi-to improved GI symptoms to the level prior to pirfenidone therapy. Plasma levels of des-acyl-ghrelin and acyl-/des-acyl-ghrelin ratio changed significantly at 8 weeks compared to 2 weeks. GI adverse events due to PFD were most severe in the first 2 weeks of treatment at a dose of 600 mg/day, and both reflux and dismotility symptoms deteriorated, but the drug was well tolerated at 1200 mg/day. Rikkunshi-to contributed to improvement of GI symptoms, but plasma ghrelin levels did not reflect the improvement of GI symptoms.

Detailed features of palisade vessels as a marker of the esophageal mucosa revealed by magnifying endoscopy with narrow band imaging.

The palisade vessels present at the distal end of the esophagus are considered to be a landmark of the esophagogastric junction and indispensable for diagnosis of columnar-lined esophagus on the basis of the Japanese criteria. Here we clarified the features of normal palisade vessels at the esophagogastric junction using magnifying endoscopy. We prospectively studied palisade vessels in 15 patients undergoing upper gastrointestinal endoscopy using a GIF-H260Z instrument (Olympus Medical Systems Co., Tokyo, Japan). All views of the palisade vessels were obtained at the maximum magnification power in the narrow band imaging mode. We divided the area in which palisade vessels were present into three sections: the area from the squamocolumnar junction (SCJ) to about 1 cm orad within the esophagus (Section 1); the area between sections 1 and 3 (Section 2); and the area from the upper limit of the palisade vessels to about 1 cm distal within the esophagus (Section 3). In each section, we analyzed the vessel density, caliber of the palisade vessels, and their branching pattern. The vessel density in Sections 1, 2, and 3 was 9.1 ± 2.1, 8.0 ± 2.6, and 3.3 ± 1.3 per high-power field (mean ± standard deviation [SD]), respectively, and the differences were significant between Sections 1 and 2 (P= 0.0086) and between Sections 2 and 3 (P < 0.0001). The palisade vessel caliber in Sections 1, 2, and 3 was 127.6 ± 52.4 µm, 149.6 ± 58.6 µm, and 199.5 ± 75.1 µm (mean ± SD), respectively, and the differences between Sections 1 and 2, and between Sections 2 and 3, were significant (P < 0.0001). With regard to branching form, the frequency of branching was highest in Section 1, and the 'normal Y' shape was observed more frequently than in Sections 2 and 3. Toward the oral side, the frequency of branching diminished, and the frequency of the 'upside down Y' shape increased. The differences in branching form were significant among the three sections (P < 0.0001). These results indicate that the density of palisade vessels is highest near the SCJ, and that towards their upper limit they gradually become more confluent and show an increase of thickness. Within a limited area near the SCJ, observations of branching form suggest that palisade vessels merge abruptly on the distal side. We have demonstrated that palisade vessels are a useful marker for endoscopic recognition of the lower esophagus.

Associations of various gene polymorphisms with toxicity in colorectal cancer patients receiving oral uracil and tegafur plus leucovorin: a prospective study.

BACKGROUND: To assess the predictive value of polymorphism in nine genes, primarily thymidylate synthase (TS) and orotate phosphoribosyltransferase (OPRT), which relates to 5-fluorouracil (5-FU) metabolism, for toxicity in patients treated with oral uracil/tegafur (UFT) plus leucovorin (LV). PATIENTS AND METHODS: We treated 99 patients with stage II or III colorectal carcinoma with oral UFT + LV. Germline DNA from patients was genotyped for 5-FU and folate metabolism-relating genes. CYP2A6, tegafur-activating enzyme, and uridine diphosphate-glucuronosyltransferase 1A1 genetic variation were also assessed. Toxicity was graded by the National Cancer Institute Common Toxicity Criteria, version 2.0. RESULTS: The multivariate logistic regression revealed that OPRT 638G>C polymorphism was associated with grade 3 diarrhea [odds ratio (OR) 19.84 for patients with the C/C homozygous type compared with patients with wild type, P = 0.014] and polymorphisms of UGT1A1 were associated with hyperbilirubinemia (OR 38.76 for homozygotes and double heterozygotes of *6 or *28 compared with wild type, P = 0.0008). No relationships were observed between TS polymorphisms and any toxicity. CONCLUSIONS: OPRT polymorphism predicts toxicity, especially grade 3 or greater diarrhea to oral UFT + LV adjuvant chemotherapy, whereas TS does not, in our study cohort. UGT1A1 polymorphism seems to be a risk factor for hyperbilirubinemia due to UFT+LV.

Phase II study of S-1 combined with irinotecan (CPT-11) in patients with advanced colorectal cancer.

OBJECTIVE: To determine the efficacy and tolerability of oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced colorectal cancer. METHODS: S-1 was administered orally at 80 mg/m(2)/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at a dose of 80 mg/m(2)/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 282 courses of treatment were administered to 40 patients, achieving complete response in 1 and partial responses in 24 with an overall response rate of 62.5% (95% CI: 47.5-77.5%). Median progression-free survival was 7.8 months (95% CI: 6.7-9.6 months). The rates of grade 3 or 4 toxicities were as follows: neutropenia 12.5%, anorexia 12.5%, fatigue 10%, and diarrhea 7.5%. CONCLUSION: Combined treatment with S-1 and irinotecan is an effective, well-tolerated and convenient regimen in patients with advanced colorectal cancer which is easily maintained.

Developing a methodology for three-dimensional correlation of PET-CT images and whole-mount histopathology in non-small-cell lung cancer.

BACKGROUND: Understanding the three-dimensional (3D) volumetric relationship between imaging and functional or histopathologic heterogeneity of tumours is a key concept in the development of image-guided radiotherapy. Our aim was to develop a methodologic framework to enable the reconstruction of resected lung specimens containing non-small-cell lung cancer (NSCLC), to register the result in 3D with diagnostic imaging, and to import the reconstruction into a radiation treatment planning system. METHODS AND RESULTS: We recruited 12 patients for an investigation of radiology-pathology correlation (RPC) in nsclc. Before resection, imaging by positron emission tomography (PET) or computed tomography (CT) was obtained. Resected specimens were formalin-fixed for 1-24 hours before sectioning at 3-mm to 10-mm intervals. To try to retain the original shape, we embedded the specimens in agar before sectioning. Consecutive sections were laid out for photography and manually adjusted to maintain shape. Following embedding, the tissue blocks underwent whole-mount sectioning (4-mum sections) and staining with hematoxylin and eosin. Large histopathology slides were used to whole-mount entire sections for digitization. The correct sequence was maintained to assist in subsequent reconstruction. Using Photoshop (Adobe Systems Incorporated, San Jose, CA, U.S.A.), contours were placed on the photographic images to represent the external borders of the section and the extent of macroscopic disease. Sections were stacked in sequence and manually oriented in Photoshop. The macroscopic tumour contours were then transferred to MATLAB (The Mathworks, Natick, MA, U.S.A.) and stacked, producing 3D surface renderings of the resected specimen and embedded gross tumour. To evaluate the microscopic extent of disease, customized "tile-based" and commercial confocal panoramic laser scanning (TISSUEscope: Biomedical Photometrics, Waterloo, ON) systems were used to generate digital images of whole-mount histopathology sections. Using the digital whole-mount images and imaging software, we contoured the gross and microscopic extent of disease. Two methods of registering pathology and imaging were used. First, selected pet and ct images were transferred into Photoshop, where they were contoured, stacked, and reconstructed. After importing the pathology and the imaging contours to MATLAB, the contours were reconstructed, manually rotated, and rigidly registered. In the second method, MATLAB tumour renderings were exported to a software platform for manual registration with the original pet and ct images in multiple planes. Data from this software platform were then exported to the Pinnacle radiation treatment planning system in DICOM (Digital Imaging and Communications in Medicine) format. CONCLUSIONS: There is no one definitive method for 3D volumetric RPC in nsclc. An innovative approach to the 3D reconstruction of resected nsclc specimens incorporates agar embedding of the specimen and whole-mount digital histopathology. The reconstructions can be rigidly and manually registered to imaging modalities such as ct and pet and exported to a radiation treatment planning system.

Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).

BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.

Association between reflux oesophagitis and features of the metabolic syndrome in Japan.

BACKGROUND: There have been many reports about the relationship between reflux oesophagitis and obesity, but not the metabolic syndrome. AIM: To review upper gastrointestinal endoscopic findings and screening data obtained in healthy subjects, and assess relations between reflux oesophagitis and features of the metabolic syndrome. METHODS: In 3599 men and 1560 women, the prevalence of reflux oesophagitis was assessed in relation to the age, body mass index, blood pressure, triglycerides and fasting blood glucose. Logistic regression analysis was used to calculate odds ratio for risk factors. RESULTS: The overall prevalence of reflux oesophagitis was 4%, and it increased with age in women. Prevalence of reflux oesophagitis increased significantly with an increase of body mass index, blood pressure, triglycerides and fasting blood glucose. On multivariate analysis, male sex (odds ratio: 2.5; 95% confidence interval: 1.6-3.8), obesity (1.9; 1.4-2.5), hyperglycaemia (1.7; 1.2-2.4) and hypertension (1.5; 1.1-2.1) were independent risk factors for reflux oesophagitis. Among both men and women, those with reflux oesophagitis were significantly more likely to have two or more of these risk factors than non-reflux oesophagitis subjects. CONCLUSIONS: Components of the metabolic syndrome are associated with the occurrence of reflux oesophagitis. Therefore, some risk factors may be common to reflux oesophagitis and the metabolic syndrome.

Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced colorectal cancer.

PURPOSE: To determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan plus S-1 in advanced colorectal cancer. PATIENTS AND METHODS: S-1 was administered orally at 80 mg/m2/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 60 mg/m2/day, stepping up to 80, 100, 120 or 140 mg/m2/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 20 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 100 mg/m2, because 2 of 3 patients developed dose-limiting toxicities, such as anorexia, fatigue and diarrhea. Therefore, the recommended dose of CPT-11 was set at 80 mg/m2. Tumor responses were seen in 8 of 14 patients with measurable lesions. CONCLUSION: A combination of S-1 with CPT-11 is safe and can be recommended for further phase II studies in patients with advanced colorectal cancer.

High-viscosity liquid meal accelerates gastric emptying.

Adding pectin to an elemental formula increases its viscosity through gelatinization, thus presumably preventing gastro-oesophageal reflux and aspiration pneumonia. We investigated the influence of the viscosity of an elemental formula on gastric emptying. Eleven healthy volunteers underwent three tests at intervals of >1 week. After fasting for >8 h, each subject received a test meal (enteral nutrition solution, enteral solution plus pectin, or water). Then gastric emptying (continuous (13)C breath test), gastro-oesophageal intraluminal pressures, oesophageal pH, and blood levels of glucose, insulin and gastrin were all measured simultaneously. The gastric emptying coefficient was significantly increased by adding pectin to enteral nutrition (3.01 +/- 0.10 vs 2.78 +/- 0.10, mean +/- SE, P < 0.05). The antral motility index was also significantly higher with pectin than without at 45-60 min and 60-75 min after the test meal (526 +/- 237 vs 6.5 +/- 4.6 mmHg s(-1) and 448 +/- 173 vs 2.3 +/- 2.3 mmHg s(-1) respectively; P < 0.05). Plasma glucose was significantly higher with pectin than without it at 60 min after ingestion (141.5 +/- 6.03 vs 125.8 +/- 4.69 microM mL(-1), P < 0.05). In healthy individuals, pectin increased the viscosity of enteral nutrition and accelerated gastric emptying.

Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma.

Matrix metalloproteinase-7 (matrilysin) has been implicated in tumor invasion and metastasis as well as tumor initiation and growth. In this study, we analyzed an association between immunohistochemically detected matrilysin expression at the invasive front in esophageal squamous cell carcinomas and clinicopathological characteristics and determined whether matrilysin predicts recurrence and/or survival Matrilysin expression at the invasive front was detected in 49% of 100 carcinoma tissues and was associated with the depth of invasion (P < 0.0001), advanced tumor stage (P = 0.0159), recurrences (P = 0.0002), and recurrences within the first postoperative year (P = 0.002). Patients with matrilysin-positive carcinoma had a significantly shorter disease-free and overall survival time than did those with a matrilysin-negative one (P < 0.0001). Matrilysin remained a significant predictive value for disease-free and overall survival in multivariate analysis, including conventional clinicopathological factors (P = 0.0007 and 0.0004, respectively). Our results suggest that matrilysin may play a key role in the progression of esophageal carcinoma and that its detection may be useful for the prediction of recurrence and poor prognosis and, possibly, for selecting patients for anti-matrix metalloproteinase therapy.

Adult T cell leukemia with atypical surface phenotypes: clinical correlation.

The leukemic cells of 57 patients with adult T cell leukemia (ATL) were analyzed for their immunologic surface markers. Forty-four cases showed normal mature inducer/helper T cell phenotype (typical group: E-RFC+, Leu-1+, 2a-, 3a+ MASO36c-), but the other 13 cases showed unusual surface phenotypes (variant group) and could be subdivided into several groups (V1 to V5). Four cases had absent or low Leu-1 positivity (V1: E-RFC+, Leu-1-, 2a-, 3a+, MASO36c-), while two other cases with low Leu-1 positivity had both Leu-2a and 3a, a characteristic of cortical thymocytes, but were unreactive with MASO36c (V2: E-RFC+, Leu-1-, 2a+, 3a+, MASO36c-). Three cases lacked both Leu-2a and 3a despite having other T cell markers (V3: E-RFC+, Leu-1+, 2a-, 3a-, MASO36c-). The next three cases had low rosette-forming ability with sheep RBCs (V4: E-RFC-, Leu-1- approximately +, 2a- approximately +, 3a+, MASO36c-). Interestingly, one other case showed high reactivity against anti-Leu-7, which is believed to be one of the monoclonal antibodies directed against natural killer cells (V5: E-RFC+, Leu-1+, 2a-, 3a+, 7+, MASO36c-). Clinical and hematologic differences between the typical group and variant group were investigated, and it was found that the variant group (excluding V5) have statistically significant (P less than .002) higher serum lactic dehydrogenase (LDH) activity. The overall survival in the variant group was worse than in the typical group, but it was not quite statistically significant (P = .072). The median survival time was eight months for typical cases and only four months for variant cases; six cases died within two months. The V5 case was unusual not only because the patient's leukemic cells have Leu-7 antigen but also because she survived more than nine years after initial diagnosis. There seems to be some correlation between phenotypic diversity of ATL cells and prognosis.

Variant parameter values-as defined by the Chicago Criteria-produced by ManoScan and a new system with Unisensor catheter.

BACKGROUND: Recently reported normal values for esophageal motility obtained by high-resolution manometry (HRM) using a system with a Unisensor catheter were significantly different from those obtained by the ManoScan(®) , which could result in a wrong diagnosis. To clarify whether these differences were due to system or subject differences, we compared the manometric parameter values between ManoScan and a new system with a Unisensor catheter (Starlet) in the same subjects. METHODS: A total of 103 volunteers without any symptoms related to esophageal motility disorders were recruited. Esophageal HRM was performed using both the ManoScan and the Starlet in all subjects. Data from the ManoScan were analyzed using ManoView, and data from the Starlet were analyzed by a program with e-sleeve function. Integrated relaxation pressure, distal contractile integral, contractile front velocity (CFV), intrabolus pressure, and distal latency were calculated by both analyzing programs, and the values of these parameters were compared between the two systems by a signed rank test. KEY RESULTS: Data from a total of 97 participants were analyzed. The values of all parameters, except CFV, measured by the Starlet were significantly higher than those obtained by the ManoScan (p < 0.01). CONCLUSIONS & INFERENCES: Both systems can measure esophageal motility appropriately; nevertheless, we confirmed that the two systems showed different values of the parameters defined by the Chicago criteria. These differences should be recognized to evaluate esophageal motility precisely.

Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

Morphology and function of isolated hepatocytes transplanted into rat spleen.

Hepatocytes isolated by the collagenase digestive method were transplanted into the spleens of syngeneic rats. Morphology and function of the hepatocytes in the spleen were investigated for 12 to 17 months after transplantation. The transplanted hepatocytes proliferated and reconfigured in the spleen without direct perfusion of portal venous blood and with the presence of an intact host liver. Fourteen to 17 months after transplantation, the hepatocytes which had formed a demarcated nodule occupied approximately 40% of the area of the splenic parenchyma without undifferentiation on microscopic examination. However, the weight of the hepatized spleen did not increase beyond the weight of a normal spleen and the weight of the host liver that had normal morphology also did not differ from a normal liver. Light and electron microscopic studies demonstrated differentiated cord structure and normal architecture for each heptocyte. Furthermore, the hepatized spleen synthesized albumin and glycogen as demonstrated by immunofluorescence and histochemical studies. Ammonia tolerance and indocyanine green clearance tests revealed functioning hepatocytes in the spleen proper. These results indicate that our experimental model lends itself well to investigations in cell growth mechanism and that hepatocellular transplantation has potential clinical application to compensate for impaired hepatic function.

Phenotypic diversity and prognosis of adult T-cell leukemia.

We examined phenotypically 107 patients with adult T-cell leukemia (ATL), using a panel of monoclonal antibodies, in order to clarify the occurrence of aberrant phenotypes, and to determine the correlation between phenotypic diversity and prognosis. The incidence of the typical (CD4+.CD8-) phenotype, the double-negative (CD4-.CD8-), the double-positive (CD4+.CD8+), and the CD8-positive (CD4-.CD8+) phenotypes was 81%, 7%, 7%, and 4%, respectively. The median survival time (MST) for all patients was 10.0 months with 17% survival at 2 years. The patients with typical phenotypes had a 10.2 month MST with 20% survival at 2 years, significantly better than the patients with the unusual phenotypes whose MST were 4.9, 7.8, and 2.6 months, respectively, for the double-negative, double-positive, and CD8-positive phenotypes. Lack of antigens reactive with CD2, CD3, CD5, and WT31 monoclonal antibody panels was one factor in bad prognosis, but the presence of CD4 and CD8 antigen abnormalities was much more significant.

De novo acute myeloid leukemia in the elderly; a consistent fraction of long-term survivors by standard-dose chemotherapy.

To clarify the characteristics of de novo acute myeloid leukemia (AML) among the elderly, we reviewed 112 patients over 60 years old (median age 72 years) who were treated at hospitals in Nagasaki Prefecture with a population of 1.5 million between 1987 and 1994. Reclassification of morphological diagnosis revealed that the proportion of M3 was lower but that of M6 and the incidence of cases with trilineage dysplasia (TLD), known as poor prognostic features, were higher in the elderly than in patients less than 60 years old. Similarly, chromosomal data showed a lower frequency of favorable karyotypes such as t(8;21) and t(15;17) in the elderly. The overall survival of all 112 patients was 10.3% at 5 years. Multivariate analysis indicated that good performance status (PS), low WBC at diagnosis, standard dose multi-drug chemotherapy and all-trans retinoic acid (ATRA) treatment for M3 patients, and morphological findings without TLD were significantly correlated with longer survival. Most of the long-term survivors were found among those who received standard dose therapy in this series, although no consensus has been established how to treat elderly AML patients. We propose that a prospective controlled trial is necessary to confirm the role of standard dose chemotherapy for elderly patients with de novo AML.

Matrix metalloproteinase matrilysin (MMP-7) participates in the progression of human gastric and esophageal cancers.

Matrilysin is one of matrix metalloproteinases, which is supposed to have a specific role in tumor progression. Expression of matrilysin was investigated in gastric and esophageal cancers by an immunohistochemical examination. Matrilysin was expressed in all esophageal squamous cell carcinomas (13/13) and in the majority of gastric adenocarcinomas (31/35, 89%). The positive staining was observed in tumor cells of cancerous tissues. In gastric cancers, there were significant statistical correlations between matrilysin expression at the invasive front and nodal metastasis or advanced stage. These results suggest that overexpression of matrilysin has an important role in the progression of upper gastrointestinal cancers.

Review article: diagnosis and investigation of gastro-oesophageal reflux disease in Japanese patients.

Gastro-oesophageal reflux disease (GERD) encompasses a wide range of disorders defined by either reflux-related symptoms or by complications of gastro-oesophageal reflux. The most characteristic GERD symptoms are heartburn and acid regurgitation. Patients with these symptoms are in most cases easily identifiable and diagnosis is made on the basis of symptoms alone. For patients with a decreased frequency of heartburn, diagnosis is more difficult, and endoscopy is the single best test for diagnosis of GERD. A major difference between the West and Asia is the frequency of endoscopic investigation. In Japan, the earlier high prevalence of stomach cancers resulted in the increased use of endoscopy as an investigational tool for dyspeptic symptoms and today endoscopy continues to be widely available as a diagnostic tool. However, the overall sensitivity of endoscopy for the diagnosis of GERD is less than 50% since not all patients will have oesophagitis at the time of endoscopy. Ambulatory pH monitoring is therefore a frequently used diagnostic tool as it allows correlation between reflux events and symptoms, and is especially useful in patients with atypical or extraoesophageal symptoms. Oesophageal manometry is also an excellent test to evaluate oesophageal function and to measure sphincter pressure and while it may not provide an unequivocal diagnosis of GERD it is a useful tool with which to evaluate oesophageal function.