Intestinal amoebiasis in a patient with acute graft-versus-host disease after allogeneic bone marrow transplantation successfully treated by metronidazole.

Amoebiasis has rarely been reported in patients undergoing hematopoietic stem cell transplantation, although it is a world-wide infection and extremely common. We present a case of intestinal amoebiasis unexpectedly revealed by colonoscopy after allogeneic bone marrow transplantation from a human leukocyte antigen-mismatched unrelated donor for acute myeloid leukemia arising from chronic myelomonocytic leukemia and successfully treated by metronidazole.

S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial.

BACKGROUND: The ACTS-CC 02 trial demonstrated that S-1 plus oxaliplatin (SOX) was not superior to tegafur-uracil and leucovorin (UFT/LV) in terms of disease-free survival (DFS) as adjuvant chemotherapy for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). We now report the final overall survival (OS) and subgroup analysis according to the pathological stage (TNM 7th edition) for treatment efficacy. PATIENTS AND METHODS: Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m2 of UFT and 75 mg/day of LV on days 1-28, every 35 days, five cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80 mg/m2/day of S-1 on days 1-14, every 21 days, eight cycles). The primary endpoint was DFS and the patients' data were updated in February 2020. RESULTS: A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the final analysis. With a median follow-up time of 74.3 months, the 5-year DFS rate was 55.2% in the UFT/LV group and 58.1% in the SOX group [stratified hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.76-1.11; P = 0.3973], and the 5-year OS rates were 78.3% and 79.1%, respectively (stratified HR 0.97; 95% CI 0.76-1.24; P = 0.8175). In the subgroup analysis, the 5-year OS rates in patients with T4N2b disease were 51.0% and 64.1% in the UFT/LV and SOX groups, respectively (HR 0.72; 95% CI 0.40-1.31). CONCLUSION: Our final analysis reconfirmed that SOX as adjuvant chemotherapy is not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer. The 5-year OS rate was similar in the UFT/LV and SOX groups.

Histological criteria for "intraepithelial squamous cell carcinoma" of the esophagus: continued dialogue between Ukrainian and Japanese pathologists.

BACKGROUND: Patients with esophageal squamous cell carcinoma (SCC) have a poor prognosis mostly due to the late diagnosis. A morphological method is still the main diagnostic method for SCC. The aim of the study was to find out which histological criteria, namely Western or Japanese criteria, for early stage SCC are used by pathologists in Ukraine as compared with their Japanese colleagues. METHODS: 14 Ukrainian and 6 Japanese pathologists have participated in this study. Virtual slides for research were provided by National Cancer Research Center (Tokyo, Japan) in 2018. Each of the pathologists has used these slides and presented the conclusion via the Internet. RESULTS: Essential diagnostic discrepancies were revealed: a number of biopsy specimens was diagnosed by Japanese pathologists as "noninvasive carcinoma", while Ukrainian pathologists classified the specimens as high-grade or low-grade dysplasia, indefinite for neoplasia, or reactive/regenerative lesions. CONCLUSION: The adoption of a unified concept of criteria for non-invasive (intraepithelial) carcinoma underlies early endoscopic/surgical treatment, which significantly increases the survival rate of patients with SCC. A solid common approach to the diagnosis between Western and Japanese pathologists, as well as endoscopists, is necessary to ensure timely treatment and increase survival rate of patients with SCC.

Successful therapeutic use of a single-dose of rituximab on relapse in adults with minimal change nephrotic syndrome.

Minimal change nephrotic syndrome (MCNS) usually is considered to have a good renal prognosis, but the frequency of relapses is a therapeutic challenge to physicians. The treatment of patients with multiple relapses remains a matter of controversy, because few controlled studies are available. We report the case of a 25-year-old man who experienced relapses of MCNS. Single-dose rituximab therapy (total dose 500 mg) was given during the fourth relapse. Complete remission occurred 10 days later, when no CD19/20-positive B cells were detected in the blood. This the first report of efficacy of single-dose rituximab therapy to treat multi-relapsing MCNS in an adult patient.

Three major dietary patterns are all independently related to the risk of obesity among 3760 Japanese women aged 18-20 years.

OBJECTIVE: To examine associations between dietary patterns and obesity. DESIGN: Cross-sectional study. SUBJECTS: A total of 3760 Japanese female dietetic course students aged 18-20 years from 53 institutions in Japan. MEASUREMENTS: Diet was assessed over a 1-month period with a validated self-administered diet history questionnaire with 148 food items, from which 30 food groups were created and entered into a factor analysis. Body mass index (BMI) was calculated from self-reported body height and weight. RESULTS: Mean BMI (+/-s.d.) was 20.9+/-2.8 kg m(-2). Four dietary patterns were identified. After adjustment for several confounding factors and total energy intake, the 'Healthy' pattern, characterized by high intakes of vegetables, mushrooms, seaweeds, potatoes, fish and shellfish, soy products, processed fish, fruit and salted vegetables, was significantly associated with a lower risk of BMI> or =25 (odds ratio of the highest quintile vs lowest, 0.57; 95% confidence interval: 0.37-0.87; P for trend <0.05). In contrast, the 'Japanese traditional' pattern, characterized by high intakes of rice, miso soup and soy products, and the 'Western' pattern, characterized by high intakes of meats, fats and oils, seasonings, processed meats and eggs, were both significantly associated with an increased risk of BMI> or =25 (OR: 1.77; 95% CI: 1.17-2.67; P for trend <0.01 and OR: 1.56; 95% CI: 1.01-2.40; P for trend=0.04, respectively). CONCLUSION: Three major dietary patterns, Healthy, Japanese traditional and Western, were all independently and significantly related to the risk of obesity even among a relatively lean young Japanese female population.

Association between dietary fiber, water and magnesium intake and functional constipation among young Japanese women.

OBJECTIVE: Most research on constipation has focused on dietary fiber intake. Here, we examined the intake of water and magnesium, nutrients possibly associated with constipation, as well as that of dietary fiber in relation to constipation. DESIGN: Cross-sectional study. SUBJECTS: A total of 3835 female Japanese dietetic students aged 18-20 years from 53 institutions in Japan. METHODS: Dietary intake was estimated with a validated, self-administered diet history questionnaire. Functional constipation was defined using the Rome I criteria. RESULTS: The prevalence of functional constipation was 26.2%. Neither dietary fiber intake (mean=6.4 g/4186 kJ) nor intakes of total water and water from fluids were associated with constipation. Conversely, low intake of water from foods was associated with an increasing prevalence of constipation. In comparison with women in the first (lowest) quintile, the multivariate adjusted odds ratio (OR) (95% confidence interval (CI)) for women in the second, third, fourth, and fifth quintiles were 0.72 (0.57, 0.90), 0.78 (0.62, 0.98), 0.71 (0.56, 0.89), and 0.77 (0.61, 0.97), respectively (P for trend=0.04). Additionally, low magnesium intake was associated with increasing prevalence of constipation. Compared with women in the first quintile, the multivariate adjusted OR (95% CI) for women in the second, third, fourth and fifth quintiles were 0.70 (0.56, 0.88), 0.75 (0.60, 0.95), 0.73 (0.58, 0.92) and 0.79 (0.63, 0.996), respectively (P for trend=0.09). CONCLUSIONS: Low intakes of water from foods and magnesium are independently associated with an increasing prevalence of functional constipation among a population whose dietary fiber intake is relatively low.

Dietary fiber intake, dietary glycemic index and load, and body mass index: a cross-sectional study of 3931 Japanese women aged 18-20 years.

OBJECTIVE: Few observational studies have investigated dietary fiber intake and dietary glycemic index (GI) and glycemic load (GL) simultaneously in relation to obesity, particularly in non-Western populations. We examined the associations between dietary fiber intake and dietary GI and GL, and body mass index (BMI) in young Japanese women. DESIGN: Cross-sectional study. SUBJECTS: A total of 3931 female Japanese dietetic students aged 18-20 years from 53 institutions in Japan. METHODS: Dietary fiber intake and dietary GI and GL (GI for glucose=100) were assessed by a validated, self-administered, diet history questionnaire. BMI was calculated from self-reported body weight and height. RESULTS: Mean values of BMI, dietary fiber intake, dietary GI and dietary GL were 21.0 kg/m(2), 6.5 g/4186 kJ, 65.1 and 82.1/4186 kJ, respectively. White rice (GI=77) was the major contributor to dietary GI and GL (45.8%). After controlling for potential dietary and nondietary confounding factors, dietary fiber intake was negatively correlated with BMI (adjusted mean=21.1 kg/m(2) in the lowest and 20.7 kg/m(2) in the highest quintiles; P for trend=0.0007). Conversely, dietary GI and GL were independently positively correlated with BMI (20.8 and 21.2 kg/m(2); P for trend=0.03, and 20.5 and 21.5 kg/m(2); P for trend=0.0005, respectively). CONCLUSIONS: Dietary fiber intake showed an independent negative association with BMI, and dietary GI and GL showed an independent positive association with BMI among relatively lean young Japanese women.

Serum ferritin level is a prognostic marker in patients with peripheral T-cell lymphoma.

INTRODUCTION: The prognostic value of serum ferritin level in patients with peripheral T-cell lymphoma (PTCL) remains unknown. METHODS: We retrospectively analyzed clinical data from 78 consecutive patients with newly diagnosed PTCL that were treated with anthracycline-containing regimens between 1998 and 2011. RESULTS: The patients consisted of 50 males and 28 females with a median age of 64 years (range, 16-83 years). The subtypes of PTCL were 39 PTCL, not otherwise specified and 39 angioimmunoblastic T-cell lymphoma (AITL). The median observation period for the surviving patients was 50 months. The overall survival (OS) was poorer in patients with serum ferritin level above the upper normal limit (n = 28), compared with patients with serum ferritin level within normal range (n = 50; 4-year OS: 23% vs. 72%; P < 0.001). In the multivariate analysis, poor performance status (P = 0.006) and elevated serum ferritin level (P = 0.018) were independent risk factors for poor OS. CONCLUSION: Serum ferritin level is a useful prognostic marker for PTCL.

Response of microbodies in Morris hepatoma 9618A to clofibrate.

Regulation of the formation of microbodies in Morris hepatoma 9618A was studied by examination of the response of the organelles to clofibrate. The fine structures of microbodies in the hepatoma cells closely resembled those in hepatocytes of normal adult rats. In clofibrate-treated rats, the tumor cells showed a slight increase in the size of microbodies and in catalase activity; however, the tumor microbodies did not increase in number. In contrast, in adult clofibrate-treated rats and rats on the day of birth whose mothers received clofibrate during the gestation period, the hepatocytes showed microbodies that were greater in both number and size, and the catalase activity in the liver was definitely elevated.

Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas.

Intestinal metaplasia of the human stomach was classified into two types, complete and incomplete. The complete type was associated with the intestinal marker enzymes sucrose alpha-D-glucohydrolase, alpha, alpha-trehalase, aminopeptidase (microsomal) (APM), and alkaline phosphatase (ALP). Tissue of this type contained goblet cells and Paneth's cells but not high-iron diamine (HID)-positive mucin staining with HID-Alcian blue. The incomplete type of intestinal metaplasia was associated with sucrose alpha-D-glucohydrolase, APM, goblet cells, and HID-positive mucin but not with alpha, alpha-trehalase, ALP, or Paneth's cells. For the examination of the distribution of the complete and incomplete types in 84, 27, and 16 resected specimens of human stomach with gastric carcinoma, gastric ulcer, and duodenal ulcer, respectively, disaccharidases were located with Tes-Tape. Specimens with intestinal metaplasia were divided into three classes: complete type only (class I), incomplete type only (class II), and a mixture of areas of the complete and incomplete types (class III). Of the 84 specimens from patients with gastric carcinoma, intestinal metaplasia was found in 76 (01%), and the percentages of specimens of classes I, II, and III were 32, 22, and 46, respectively. In these specimens, the percent incidence of class I increased and that of class II decreased with age. Of the 27 specimens from patients with gastric ulcer, 16 (59%) shopwed intestinal metaplasia and 10 of the 16 (63%) specimens were of class II. Of the 16 specimens from patients with duodenal ulcer, only 3 (19%) specimens showed intestinal metaplasia and all of them were of class II. The relationships of the complete and incomplete types of intestinal metaplasia to gastric carcinoma wre studied in 26 foci of minute carcinoma of the stomach less than 5 mm in largest diameter. Nineteen of 20 (05%) foci of the intestinal type of minute carcinoma were surrounded by intestinal metaplasia and 16 foci (80%) were surrounded by the incomplete type of intestinal metaplasia.

Changes in peroxisomes in preneoplastic liver of rats induced by 3'-methyl-4-dimethylaminoazobenzene.

Histochemical investigations used the 3,3'-diaminobenzidine reaction to demonstrate the catalase activity and thus variations in numbers of peroxisomes, and electron microscopic examinations were made of hyperplastic liver lesions in rats fed 0.06%3'-methyl-4-dimethylaminoazobenzene. At the 10th week of carcinogen feeding, hyperplastic lesions (hyperplastic foci, areas, and nodules) appeared and advanced to further stages. Most of the foci and some of the areas and nodules showed very low catalase activity and, correspondingly, a small number of peroxisomes. When rats were administered ethyl-alpha-p-chlorophenoxyisobutyrate, most of the foci, areas, and nodules showed a moderate increase in catalase activity and in peroxisome number. Hyperplastic foci seemed to grow larger with time to form hyperplastic areas and/or nodules, mostly accompanying maturation as well as proliferation of the hepatocytes involved. Maturation is well characterized by an increase in the endogenous level of catalase and in the number of peroxisomes, as well as by an enhancement of the responsiveness to ethyl-alpha-p-chlorophenoxyisobutyrate. However, there was a small proportion of lesions in which all cells or some cells did not mature and thus were considered persistently altered. It is suggested that these altered cells serve mainly as intimate precursors of hepatomas.

Sequential studies on the histopathogenesis of gastric carcinoma in rats by a weak gastric carcinogen, N-propyl-N'-nitro-N-nitrosoguanidine.

Sequential studies were made on the histopathologic changes in the glandular stomach of rats induced by a weak carcinogen. N-propyl-N'-nitro-N-nitrosoguanidine (PNNG). Fiftyfour rats were given 100 micrograms/ml of PNNG in their drinking water for 44 weeks, and then normal tap water until the end of the experiment. Rats were killed at intervals between week 1 and week 88. No marked atrophy or ulceration of the mucosa was found between week 1 and the end of the experiment. Focal intestinal metaplasia was found in week 19 and its incidence increased during the experiment. Adenocarcinoma in situ with extreme cellular atypia was found in mucosa with a normal appearance in week 67. An adenocarcinoma invading the submucosa was found in week 69, and one invading the serosa in week 88. All these pathological lesions were found on the anal side of the pyloric region. No pathologic changes were found in the fundic region. The sequential changes of the mucosa of the glandular stomach induced by this weak gastric carcinogen, PNNG, were very different from those induced by the potent gastric carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Gastric carcinoma induced by PNNG seems to be more similar to human gastric cancer than that induced by MNNG.

Eosinophilic bodies in pyloric and Brunner's gland cells.

A previously unreported cell phenotype occurred in the pyloric and Brunner glands in two gastrectomy specimens. The cells were characterised by homogeneous, eosinophilic material in the cytoplasm. The eosinophilic material had an abnormally strong reactivity for Cystatin C, a protein found recently in the normal secretion of pyloric and Brunner's gland cells. The reason for the apparent cytoplasmic accumulation of cystatin C in the two patients described remains unclear.

Multiple primary carcinoma of the oesophagus.

A retrospective evaluation of 239 patients with primary oesophageal carcinoma who underwent oesophagectomy without preoperative treatment revealed 45 cases (18.8%) of multiple primary oesophageal carcinoma (MPEC). The average age of the patients with MPEC was significantly lower than that of patients with single primary oesophageal carcinoma (SPEC) (P = 0.005). The incidence of association with pharyngeal malignancy was higher in patients with MPEC than in those with SPEC (P = 0.080). The number of patients in the category representing a combination of heaviest alcohol and cigarette use was significantly higher in the MPEC patients (P = 0.035). The high incidence of MPEC points to a need for careful checking of the oesophagus at the time of surgical treatment for oesophageal carcinoma. Low age at onset, a combination of heavy smoking and drinking, and association with pharyngeal malignancy are considered to be high-risk factors for MPEC.

Comparative studies on the histogenesis of squamous carcinoma of esophagus in mice and in human subjects.

Histological changes occurring in the esophageal mucosa of 110 C57b1 mice, after protracted topical treatment with diethylnitrosamine, were compared to those present in human esophagus in three patients operated for early esophageal cancer. Both in mice and in human material, the histological changes were classified into slight, moderate or severe dysplasia, carcinoma in situ, questionable invasive carcinoma and invasive carcinoma. Starting from moderate dysplasia, the epithelial-stroma border became irregular with bud formation bulging into the stroma. The findings strongly suggest an association between the degree of cellular atypia, the formation of epithelial buds, and progression towards invasive carcinoma.

Extended intestinal metaplasia. A survey of 1392 gastrectomies from dwellers of the Pacific basin.

BACKGROUND: To assess the extent of gastric intestinal metaplasia (IM) in gastrectomy specimens in populations of the Pacific basin having different incidence of gastric carcinoma. MATERIALS AND METHODS: One thousand three hundred and nine-two gastrectomies were investigated: 1088 had a gastric carcinoma and 304 miscellaneous gastric diseases. Twenty-one thousand three hundred and fourteen histological sections were reviewed under low-power (4X). IM was either spotty (SIM) or extended (EIM= encompassing one or more entire low-power fields/section). Widespread IM (WIM) was regarded as EIM if present in > or =5 histological sections. RESULTS AND CONCLUSION: The percent of gastrectomies harboring a carcinoma increased significantly with increasing age more notably in those with diffuse carcinomas (DC) than in those with intestinal carcinomas (IC). The percent of gastrectomies with EIM was significantly higher in specimens with IC than with DC, particularly among elderly patients, and in specimens from countries with a high cancer incidence. The percent of gastrectomies with WIM was higher in specimens having IC than in those having DC. Migration per se did not influence the frequency of specimens with EIM in elderly Japanese patients: Japanese migrants to Hawaii had a similarly high frequency of EIM as those dwelling in Japan. Japanese patients with a gastric carcinoma showed atypical mitoses in areas with EIM far from the tumor, suggesting that cellular mutation(s) play a role in the evolution of EIM towards gastric dysplasia and carcinoma in that ethnic group. The drawback of gastric biopsies in assessing the extent of gastric intestinal metaplasia and, thereby, estimating possible cancer risk in long-term studies has been stressed.

Comparison of macroscopic appearance and estrogen receptor-alpha regulators after gene alteration in human endometrial cancer.

The existence of two types of endometrial cancer (hyperplasia-associated type [type I] and atrophy-associated type [type II]) is well established. To test if different molecular genetic pathways are involved in the pathogenesis of type I and II disease, we examined pathologic features and the genetic alterations of K-Ras, MDM2 and p53 (which are considered to be involved in regulation of the estrogen receptor-alpha) in human endometrial tissue samples using several modified PCR methods. We found a significant difference in histologic grade (P < 0.001), degree of invasion (P < 0.001), stage grouping (P < 0.001) and estrogen receptor status (P < 0.01) between type I and II cases. There was a tendency for cases with K-Ras point mutations to be of type I, and for cases with the p53 point mutation to be of type II; however, we found that these mutations or alternative splicing of MDM2 was rarely involved and there was no significant difference in frequency of these alterations between types I and II. There must therefore be another structural or functional difference of Ras, MDM2 or p53 between type I and type II cancer. These unknown factors may be responsible for the difference between estrogen-dependent and estrogen-independent growth in human endometrial cancer.

Tubular osteopontin expression in patients with ANCA-associated glomerulonephritis.

OBJECTIVE: To elucidate the role of osteopontin (OPN) in monocyte recruitment in crescentic glomerulonephritis, we investigated immunohistochemical localization of OPN in the kidney and its correlation with clinical and histopathologic parameters in biopsy specimens of patients with myeloperoxidase antineutrophil cytoplasmic autoantibody- (MPO-ANCA) associated glomerulonephritis. METHODS: Twelve patients with MPO-ANCA-associated glomerulonephritis were enrolled in this study. Clinical parameters such as creatinine clearance and urinary protein excretion of each patient were obtained at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining using the LSAB method. Five cortical interstitial fields randomly selected at original magnification x 200 were assessed using a computer-assisted color image analyzer. Tubular OPN expression was assessed as the percentage of positive area in the tubulointerstitium. Double immunofluorescent staining using antibodies against OPN and alpha(v)beta3 was performed. RESULTS: In all of the cases studied, OPN was occasionally localized within the glomeruli, and expressed slightly in proximal tubular epithelium and significantly in distal tubular epithelium. Tubular OPN expression tended to be promoted in the interstitium infiltrating by numerous monocytes/macrophages. The extent of tubular OPN expression was positively correlated with serum ANCA titers and urinary OPN concentrations. Enhanced alpha(v)beta3 expression appeared in the distal tubular epithelium expressing OPN. CONCLUSION: These results suggest that inducible expression of OPN and alpha(v)beta3 in the tubular epithelium seems to be associated with interstitial moncyte infiltration and subsequent tubulointerstitial changes in human MPO-ANCA-associated glomerulonephritis.

Overexpression of mitogen-activated protein kinase superfamily proteins unrelated to Ras and AF-1 of estrogen receptor alpha mutation in advanced stage human breast cancer.

Transactivation of the activation function-1 (AF-1) region of the estrogen receptor alpha (ER-alpha) gene is regulated by pathway "cross-talk" from Ras mitogen-activated protein kinase (MAPK). An analysis of this system is important for solving the problem of resistance to anti-estrogen agents used in the treatment of human breast cancer. We investigated the ER-alpha and Ras gene mutations and the MAPK-related protein status in 103 cases of breast carcinoma. None of the cases showed mutations in the AF-1 region of the ER-alpha gene. Despite the extremely low frequency of K- and H-Ras mutations in codon 12 (2/103 and 0/103), Ras p21 overexpression was identified in 29.1% (30/103), suggesting that the Ras activation in almost all cases we studied was not caused by point mutations but by enhanced expression. Our immunohistochemical analysis showed that the cases with overexpression of Ras and MAPK proteins (Ras p21, ERK-1, JNK-1, and p38) had a progressive tendency towards invasive growth, advanced-stage cancer, and decreased levels of ER-alpha protein. These results suggest that enhanced MAPK activity could be one of the characteristics of advanced breast cancer and that it could be involved in the transformation into estrogen-independent growth.

A new bioactive steroidal saponin, furcreastatin, from the plant Furcraea foetida.

Microbial and plant secondary metabolites were screened for compounds that are selectively cytotoxic to mutant p53-expressing mouse fibroblasts. As a result, furcreastatin, a novel steroidal saponin, was isolated from an EtOH extract of the leaves of Furcraea foetida. Furcreastatin consisted of hecogenin as the aglycone and a hexasaccharide containing D-galactose, L-rhamnose and four D-glucose residues. The structure was determined to be (3 beta,5 alpha,25R)- 3-hydroxyspirostan-12-one 3-O-[alpha-L-Rhap-(1-->4)-beta-D-Glcp-(1-->3)-¿beta-D-Glcp-(1-->3) -beta-D- Glcp-(1-->2)¿-beta-D-Glcp-(1-->4)-beta-D-Galp] by extensive NMR spectroscopic studies. Furcreastatin decreased the viability of mutant p53-over-expressing cells with an ED50 of 4.0 micrograms/mL, and decreased that of the parental cell-line with an ED50 of 9.6 micrograms/mL.