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.

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.

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.

Epidemiology of sarcoptic mange in free-ranging raccoon dogs (Nyctereutes procyonoides) in Yokohama, Japan.

Free-ranging raccoon dogs (Nyctereutes procyonoides) from Nogeyama Zoological Gardens, Kanazawa Zoological Gardens, and Yokohama Zoological Gardens frequently rescued dogs having Sarcoptes scabiei infestation. However, the epidemiology of S. scabiei infestation has not yet been elucidated. In the present study, we investigated the epidemiology of S. scabiei infestation in raccoon dogs and its influence on the population of masked palm civets in Yokohama, Japan. We examined records of raccoon dog rescue between 1981 and 2010 and classified the dogs into the following 4 categories on the basis of the reason for rescue: dogs with S. scabiei infestation, scabies-infested dogs involved in car accidents, uninfested dogs involved in car accidents, and other reasons for rescue. We found that the number of dogs rescued due to car accidents and other reasons increased from 1989 onwards, and an S. scabiei outbreak was recorded since 1993. The infestation spread from the southern to the northern regions of Yokohama. The total number of raccoon dogs rescued annually peaked in 1995 and declined thereafter. The number of masked palm civets (Paguma larvata) rescued gradually increased with a decline in the number of raccoon dogs rescued. In the present study, we revealed the epidemiology of S. scabiei infestation in the raccoon dog. The outbreak might be induced by the increased population density, and the infestation spread immediately from the southern to the northern regions of Yokohama since 1993. Further, the population of masked palm civets may have increased due to the decrease in the population of the raccoon dog.

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.

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.

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.

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.

Hepatoid adenocarcinoma of the stomach.

Although gastric cancer occurs frequently in Japan, few cases of hepatoid adenocarcinoma, a cancer with an extremely poor prognosis, have been reported. Here, we describe a 67-year-old Japanese man referred to our hospital with suspected gastric cancer. Gastrointestinal fiberscopy revealed an elevated lesion with a central depression on the lesser curvature, extending from the antrum to the body of the stomach. On the preoperative examinations, abdominal computed tomography scan, magnetic resonance imaging, and abdominal ultrasonography revealed multiple metastases to the liver and no cirrhotic change. The serum level of alpha-fetoprotein (AFP) was markedly elevated (10,084 ng/ml). After a diagnosis of AFP-producing gastric cancer with multiple liver metastases was made, total gastrectomy, without liver resection, was performed. Microscopically, the tumor showed two main histological features. The main part of the tumor resembled moderately differentiated hepatocellular carcinoma, and the rest showed fetal-type adenocarcinoma. Some parts of the hepatoma-like lesion showed periodic acid-Schiff (PAS)-positive granules. Furthermore, the tumor showed diffuse immunohistochemical positivity for AFP, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. According to these histopathological findings, the tumor was diagnosed as hepatoid adenocarcinoma of the stomach. Although anastomotic leakage occurred postoperatively and the liver metastases have increased in size, the patient remains alive 11 months after the operation. Because of the poor prognosis for this histological type of tumor, accurate diagnosis of hepatoid adenocarcinoma is important, and long-term follow-up is required. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects.

Solitary schwannoma of the colon: report of two cases.

Some patients with gastrointestinal schwannoma (GIS) have been previously reported in the literature. However, GIS of the colon is quite rare. In addition, it is sometimes difficult to differentiate neurogenic tumors from other soft tissue tumors. We herein describe two cases of schwannoma of the colon, while also reviewing the relevant Japanese literature. The first case, a 73-year-old woman underwent a sigmoidectomy with lymph node dissection following the diagnosis of submucosal tumor. In the second case, a submucosal tumor was located in the cecum of a 44-year-old man. An endoscopic tumor resection was performed in the second case. The resected tumors measured 3.6 and 1.0 cm in maximal diameter, respectively. Microscopically, the tumors consisted predominantly of spindle-shaped cells that proliferated in an interlaced fashion. Mitosis was rarely seen in these tumors. Immunohistochemically, the tumor cells were strongly positive for S-100 protein, weakly positive for glial fibrillary acidic protein, and negative for CD34, alpha-smooth-muscle actin, and cytokeratin (CAM 5.2) in both cases. The tumors in the two cases were both diagnosed to be benign schwannoma of the colon. In general, schwannoma of the gastrointestinal tract is considered to be benign and should therefore be distinguished from other spindle-cell tumors or malignancies. Once diagnosed as schwannoma, extensive surgery should be avoided. Actually, such patients tend to show a good postoperative course with no evidence of recurrence.

Comparison between pancreatoduodenectomy and hepatopancreatoduodenectomy for bile duct cancer.

BACKGROUND/AIMS: Pancreatoduodenectomy has been accepted as a standard operative procedure for distal bile duct cancer with low operative mortality. However, hepatopancreatoduodenectomy has not been accepted as a standard treatment modality for diffuse bile duct cancer. METHODOLOGY: From December 12, 1992 to December 15, 2000, 37 patients with the diagnosis of extrahepatic bile duct adenocarcinoma (cholangiocarcinoma) underwent pancreatoduodenectomy or hepatopancreatoduodenectomy, at the department of surgery, Ibaraki Prefectural Central Hospital and the Cancer Center. The differences in indications and results of both operative procedures were investigated retrospectively. RESULTS: Thirty-day operative mortality was 0% after either pancreatoduodenectomy or hepatopancreatoduodenectomy. One- to 5-year cumulative survival rates for the 24 patients after pancreatoduodenectomy were 76.3%, 41.5%, 41.5%, 41.5%, 41.5%, respectively. One- to 4-year cumulative survival rates for the 13 patients after hepatopancreatoduodenectomy were 48.0%, 32.0%, 32.0%, 16.0%, respectively. There were no statistically significant differences between cumulative survival rates after pancreatoduodenectomy and hepatopancreatoduodenectomy either in all the patients or in patients with UICC stage IV. CONCLUSIONS: Hepatopancreatoduodenectomy should be tried for patients with diffuse bile duct cancer, because only hepatopancreatoduodenectomy has the possibility of a cure at this time.

Expression of type I, type II, and type X collagen genes during altered endochondral ossification in the femoral epiphysis of osteosclerotic (oc/oc) mice.

The osteosclerotic (oc/oc) mouse, a genetically distinct murine mutation that has a functional defect in its osteoclasts, also has rickets and shows an altered endochondral ossification in the epiphyseal growth plate. The disorder is morphologically characterized by an abnormal extension of hypertrophic cartilage at 10 days after birth, which is later (21 days after birth) incorporated into the metaphyseal woven bone without breakdown of the cartilage matrix following vascular invasion of chondrocyte lacunae. In situ hybridization revealed that the extending hypertrophic chondrocytes expressed type I and type II collagen mRNA, as well as that of type X collagen and that the osteoblasts in the metaphysis expressed type II and type X collagen mRNA, in addition to type I collagen mRNA. The topographic distribution of the signals suggests a possible co-expression of each collagen gene in the individual cells. Immunohistochemically, an overlapping deposition of type I, type II, and type X collagen was observed in both the extending cartilage and metaphyseal bony trabeculae. Such aberrant gene expression and synthesis of collagen indicate that pathologic ossification takes place in the epiphyseal/metaphyseal junction of oc/oc mouse femur in different way than in normal endochondral ossification. This abnormality is probably not due to a developmental disorder in the epiphyseal plate but to the failure in conversion of cartilage into bone, since the epiphyseal plate otherwise appeared normal, showing orderly stratified zones with a proper expression of cartilage-specific genes.

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.

Alternatively spliced MDM2 transcripts in human breast cancer in relation to tumor necrosis and lymph node involvement.

Several short forms of alternatively spliced Murine double minute 2 (MDM2) transcripts have recently been shown to correlate with high-grade malignancy in a number of human tumors. We examined the frequency of splice variants and their correlation with clinicopathological features in 60 cases of human breast cancer. Seven short forms coexpressed with wild-type mRNA were detected by nested RT-PCR. Sequencing of all the MDM2 variants demonstrated mRNA splicing which disrupted not only the conserved p53-binding domain but also, further towards the carboxy-terminus, the conserved nuclear localization sequence and/or the acidic and zinc finger domains. There was no significant correlation between the coexpression of splice variants and tumor size, histologic type or hormone (estrogen and progesterone) receptor status. However, cases with spliced MDM2 transcripts tended to be of a more aggressive type with axillary lymph node involvement and extensive necrosis in the tumors. Although the functional significance of MDM2 variants remains obscure, we anticipate that these variants will be confirmed as a novel prognostic marker in human breast cancer.

Expression of human telomerase catalytic subunit gene in cancerous and precancerous gastric conditions.

BACKGROUND AND AIMS: Telomerase activity is thought to be necessary for cellular immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic subunit (hTERT) has recently been identified, and expression of hTERT mRNA is thought to regulate activation of telomerase. To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia. METHODS: Using reverse transcription-polymerase chain reaction, hTERT gene expression was investigated in 18 gastric cancers and 60 specimens of chronic gastritis. Telomerase activity was evaluated using telomeric repeat amplification protocol. RESULTS: Sixteen of 18 (89%) gastric carcinomas expressed hTERT mRNA, and this expression was unrelated to histological type or depth of invasion. Telomerase activity was found in seven of eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and was most prominent in seven of 15 (47%) specimens of gastric mucosa with intestinal metaplasia. Expression of the hTERT gene was significantly more frequent in chronic gastritis with intestinal metaplasia than in gastritis without intestinal metaplasia (P=0.030). In addition, hTERT gene expression was not correlated with age, sex, biopsy site, histological grade of inflammatory cells, glandular atrophy and lymph follicles, or infection with Helicobacter pylori. None of eight normal gastric mucosa expressed hTERT mRNA. CONCLUSIONS: Our results indicate that hTERT mRNA is expressed in precancerous conditions as well as in gastric cancer, and that hTERT gene expression is induced at an early stage of gastric carcinogenesis.

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

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.