Human gastric carcinoma: prognosis in relation to macroscopic and microscopic features of the primary tumor.

The correlation of prognosis with various clinical and pathologic factors was studied by use of multiple stepwise linear regression analysis among 77 patients undergoing resections for gastric cancer. Factors such as depth of penetration, invasion of the duodenum, macroscopic appearance, intramural and extramural growth pattern of the cancer, lymphatic or vascular invasion, and cancer cell-free dense submucosal fibrosis around the cancerous area were significant, and independent factors correlated with the prognosis, in that order. When these factors were taken into account, other factors such as sex and age of the patient, location, size, and histologic classification of the tumor, and folds' convergence were not significant.

Relationship between serotonin transporter occupancies and analgesic effects of AS1069562, the (+)-isomer of indeloxazine, and duloxetine in reserpine-induced myalgia rats.

Serotonin (5-HT) and norepinephrine (NE) have been implicated in the mediation of endogenous analgesic mechanisms via the descending inhibitory pain pathway in the brain, and dysfunction in both the 5-HT and NE systems has been suggested as an etiology of fibromyalgia (FM). Given that 5-HT reuptake inhibition in the brain appears to be associated with pain reduction, this mechanism might exert an analgesic effect also on pain associated with FM. In this case, it would be of interest to investigate the correlation of 5-HT transporter (SERT) occupancy with in vivo analgesic effect on pain associated with FM. Here, we investigated the relationship between SERT occupancies and the analgesic effects of AS1069562, the (+)-isomer of indeloxazine, and duloxetine, which are both 5-HT and NE reuptake inhibitors (SNRIs), on muscular pain in reserpine-induced myalgia (RIM) rats, an animal model of FM-like chronic pain. We also investigated the SERT occupancy level necessary for AS1069562 and duloxetine to exert analgesic effects on muscular pain. AS1069562 and duloxetine attenuated muscular hyperalgesia in RIM rats, representing the first findings to be reported regarding the analgesic effect of AS1069562 on pain associated with FM. SERT occupancy levels of AS1069562 and duloxetine increased in both dose- and plasma and brain concentration-dependent manners. SERT occupancy levels of AS1069562 and duloxetine were significantly correlated with efficacy on muscular pain thresholds in RIM rats. This finding concerning the precise correlation of SERT occupancy with in vivo analgesic effect on pain associated with FM is reported here for the first time. SERT occupancy level above 70% was necessary for AS1069562 and duloxetine to exert significant analgesic effects on muscular pain. These results suggest that SERT occupancy level is useful in determining appropriate analgesic doses of AS1069562 and duloxetine for treating pain symptoms in FM patients.

Histologic and immunohistologic findings and prognosis of 40 cases of gastric large B-cell lymphoma.

It has been considered that gastric large B cell lymphoma mainly consists of mucosa-associated lymphoid tissue lymphoma (MALToma) with large cell transformation. However, debate continues about the cell lineage. We analyzed 61 operated cases of gastric B cell lymphoma, mainly focusing on 40 cases of diffuse large cell lymphoma (DLCL). Immunohistologically, two cases were classified as CD10-positive follicular lymphoma, 19 cases were low-grade MALToma, 11 CD10-negative DLCL with a component of low-grade MALToma (high-grade MALToma), 12 CD10-positive DLCL, and 17 CD10-negative DLCL without MALToma (pure DLCL). Lymphoepithelial lesion (LEL) was found in all -cases of high-grade MALToma, and in eight of these its invasion was confined to the mucosa and submucosa. Expression of Bcl-6 was detected in two cases of high-grade MALToma. Only two cases of CD10-positive DLCL had large cell LEL, and seven cases showed tumor invasion beyond the submucosa. All 12 cases were positive for Bcl-6, and a delicate meshwork of CD35 (Ber-MAC-DRC)-positive follicular dendritic cells was detected in eight cases. Pure DLCL of all 17 cases reached the proper muscle layer or more, and expression of Bcl-6 was detected in 10 cases. For patients with pure DLCL, overall survival was significantly (p <0.05) worse than those of high-grade MALToma and CD10-positive DLCL by Kaplan-Meier and log-rank methods. Clinical staging and Bcl-6 expression were also good prognostic factors in patients with DLCL. Three groups of gastric DLCL each had unique histologic findings, immunohistologic characteristics, and prognosis.

Neoplastic endocrine cells in carcinomas of the small intestine: histochemical and immunohistochemical studies of 24 tumors.

Endocrine cells in 24 primary carcinomas and in the nonneoplastic mucosa of the small intestine were investigated histochemically and immunohistochemically with antisera against serotonin and 10 kinds of peptide hormones. Argyrophil-positive endocrine cells were found in four of eight duodenal, all of eight jejunal, and six of eight ileal carcinomas. The density of the positive cells was higher in the ileal tumors than in the duodenal and jejunal ones. Immunoreactive endocrine cells were detected in three duodenal, six jejunal, and five ileal carcinomas. Immunoreactive serotonin cells were present most frequently and most densely without respect to the site of origin of the carcinomas. In general, the population of endocrine cells among the tumor cells was higher in the ileal carcinomas than in the duodenal and jejunal ones. The ileal carcinomas frequently and densely demonstrated somatostatin, peptide YY, neurotensin, glucagon, and glicentin cells in addition to serotonin cells. The kinds of endocrine cells and the relative frequency of each kind of endocrine cell in carcinomas of the small intestine were similar to those in the nonneoplastic mucosa from which the carcinomas originated. This is the first systematic immunohistochemical study on endocrine cells in carcinoma of the small intestine.

Peptide YY immunoreactive cells in gastrointestinal carcinoids: immunohistochemical and ultrastructural studies of 60 tumors.

The distribution and frequency of peptide YY (PYY) cells in 60 gastrointestinal carcinoids and in the nonneoplastic mucosa around the carcinoids were studied by an indirect immunoperoxidase method with anti-PYY serum. Additionally, the endocrine cell type of the PYY cells in appendiceal and rectal carcinoids was assessed by transmission electron microscopy. A few PYY cells were present in specimens of nonneoplastic mucosa from stomach, duodenum, jejunum, ileum, and appendix, with an abundance of these cells in rectal mucosa. Peptide YY cells were found in one of 13 gastric, one of 13 duodenal, one of one jejunal, zero of two ileal, three of 11 appendiceal, and 16 of 20 rectal carcinoids. All but one of the PYY-positive carcinoids were argyrophil carcinoids. Peptide YY cells in the gastric, duodenal, and jujunal carcinoids were present in small numbers. The three PYY-positive carcinoids of the appendix were composed almost totally of PYY cells, whereas those of the rectum generally contained only sporadic PYY cells. The peptide YY cells observed ultrastructurally contained almost round secretory granules (about 160 nm in average diameter), which were most consistent with D1(H) cell type granules with respect to shape and average diameter. This is the first systematic immunohistochemical and ultrastructural study of PYY cells in gastrointestinal carcinoids.

Immunohistochemical and ultrastructural studies of twelve argentaffin and six argyrophil carcinoids of the appendix vermiformis.

Endocrine cell types in 12 argentaffin and six argyrophil carcinoids and in nonneoplastic epithelia of the appendix vermiformis were investigated histochemically, immunohistochemically, and ultrastructurally. The nonneoplastic epithelia contained serotonin (Ser), peptide YY (PYY), glicentin (Gli), neurotensin (Neu), and somatostatin (So) cells in decreasing frequency. Out of 30 nonneoplastic Ser cells examined ultrastructurally, 28 cells were EC1 cells and two were non-EC cells. Eleven of 12 argentaffin carcinoids could be immunostained with anti-Ser serum and all of those 11 were composed almost totally of Ser cells. One of the 11 contained a small number of Neu cells. Ultrastructurally, 11 argentaffin carcinoids were composed predominantly of EC1 and/or ECn cells, and one was composed primarily of non-EC cells. Out of the six argyrophil carcinoids, five were argyrophil, non-argentaffin carcinoids; three consisted almost totally of PYY cells; one consisted of 60% PYY cells, 40% So cells and a few Gli cells; and one consisted of Ser cells alone. Ultrastructurally, the first four of those tumors were composed of D1 and/or L cells and the latter tumor was composed of ECn cells. The remaining one argyrophil carcinoid contained a few Ser-positive argentaffin cells and consisted almost totally of ECn cells which were found in both parts, with and without argentaffinity. It is concluded that the appendiceal carcinoids comprise two distinct groups on the basis of the main constituting cell type: Ser-positive, argentaffin carcinoids, composed of EC cells and peptide (especially of PYY)-positive, and Ser-negative, argyrophil non-argentaffin carcinoids of D1 and/or L cells.

Right-sided ulcerative colitis.

This report describes a case of right-sided ulcerative colitis in which multiple shallow ulcers and erosion with symmetric luminal stenosis were distributed segmentally from the ascending colon to the cecum, with a skip lesion composed of superficial erosions in the right half of the transverse colon. Both the rectum and the left colon were spared at the time of onset. Biopsies taken from the lesions showed non-specific inflammation, while those from the rectum and sigmoid colon showed no abnormal findings. A 5-year follow-up study was made based on radiography and endoscopy. Other inflammatory bowel diseases, such as Crohn's disease, tuberculosis, Yersinosis, Behçet's disease, and ischemic colitis were all ruled out, based on the macroscopic and microscopic findings as well as the clinical course. To our knowledge, this is the first report of right-sided ulcerative colitis that has been followed for a long period.

Prevalence of Helicobacter pylori infection and correlation between severity of upper gastrointestinal lesions and H. pylori infection in Japanese patients with Crohn's disease.

BACKGROUND: The prevalence of Helicobacter pylori infection in Crohn's disease (CD) patients was investigated to determine whether the presence and severity of gastroduodenal lesions were related to H. pylori infection. METHODS: Infection rates were compared between CD group (n = 90) and the control group (n = 525). Correlations between endoscopically detected lesions and H. pylori positive rates were investigated. The relationship between drug therapy and the prevalence of H. pylori infection was also analyzed. RESULTS: H. pylori-positive rate of the 90 CD patients attending our clinic was 16.7%, significantly lower than the rate in healthy controls (40.2%) (P = 0.0001). The involvement of H. pylori infection in the gastroduodenal lesions of CD patients was also examined. The prevalence of gastroduodenal lesions in all CD patients was high, 92.2%. The lesions observed included ulcers, erosion, and "bamboo joint-like lesions" of the stomach, and ulcers, erosion, stenosis, and elevated lesions of the duodenum. None of these lesions were found to be related to H. pylori infection. However, H. pylori infection was found to exacerbate gastric ulcers (P = 0.036). The analysis of a possible relationship between a history of drug therapy and the low prevalence of H. pylori infection in CD patients showed that the prevalence of H. pylori infection was significantly lower in patients who had received antibiotics for 2 weeks or more (P = 0.002). CONCLUSIONS: The results suggest that H. pylori infection is essentially unrelated to the gastroduodenal lesions observed in CD. It seems likely, however, that H. pylori infection may exacerbate gastric ulcers and that H. pylori can be eradicated by prolonged use of antibiotics.

Effects of basic fibroblast growth factor and ganglioside GM1 on neuronal survival in primary cultures and on eight-arm radial maze task in adult rats following partial fimbria transections.

The effects of basic fibroblast growth factor (bFGF) and ganglioside GM1 (GM1) were evaluated alone and simultaneously in two types of experiments. First, the neuronal survival of primary culture neurons from fetal rat brain was measured. Then, performance on radial maze task in adult male rats following bilateral partial Fimbria-Fornix transections (F-F lesion) was tested. In primary culture neurons, bFGF (1-10 ng/ml) supported the neuronal survival from three regions (hippocampus, cortex and septum) of embryonic rat brain. However, GM1 (0.1-10 micrograms/ml) did not support the neuronal survival from any regions. Survival of cultured neurons was not supported by addition of 0.1 ng/ml bFGF, but when bFGF (0.1 ng/ml) and GM1 (0.1, 1 microgram/ml) were given to the cultured neurons simultaneously, the number of surviving neurons increased significantly. In the eight-arm radial maze task, where only the same four arms were baited, F-F lesion produced substantial memory impairment. In this task, administration of bFGF (10 micrograms/ml) or GM1 (1 mg/ml) alone did not produce any effects. However, when they were given simultaneously, the number of working memory errors decreased significantly, in spite of no amelioration for hippocampal choline acetyl transferase (ChAT) depletion. These findings indicate that actions of bFGF may be potentiated by the addition of GM1 in both primary neuronal cultures and radial maze task performance. These results suggest that the combination of bFGF and GM1 may synergistically improve spatial memory deficits.

Do the expression of CD44, apoptosis and thymidylate synthase inhibition rate correlate with the efficacy of chemotherapy in colorectal cancer?

BACKGROUND: Tegafur-uracil(UFT;TAIHO Pharmaceutical Co.Ltd, Tokyo, Japan) is commonly used to treat digestive cancers. However, the inhibitors of metastasis in this agent have not been fully examined. To investigate a cell adhesion molecule, CD44, which may very well contribute to the pathogenesis of metastasis, we examined the association of CD44 and the thymidylate synthase inhibition rate(TSIR) with prognosis, and examined the expression of apoptosis in patients who were administrated tegafur-uracil before surgery for colorectal cancer. MATERIALS AND METHODS: This study included 66 patients who underwent curative resection of colorectal cancer. In these patients, tegafur-uracil(600 mg) was orally administered every day for 3 to 7 days before surgery, and Tegafur-uracil (400 mg) was orally administered every day for 2 years after surgery. CD44 and apoptosis were detected immunohistochemically and by the TUNNEL method, respectively. The TSIR was calculated from the total TS level, and free TS levels by modified Spears' method using fresh tumor tissue specimens. RESULTS: The TSIR of non-recurrent patients was significantly higher than that of recurrent patients(p < 0.05). The 5-year survival rate in CD44-low grade positive/negative patients (81.6%) was significantly higher than that in CD44-high grade positive patients (46.4%) (p < 0.005). The 5-year survival rate in apoptosis-high grade positive patients (89.7%) was significantly higher than that in apoptosis-low grade positive/negative patients(46.4%) (p < 0.001). With respect to the relationship between CD44 and apoptosis, the proportion of apoptosis-high grade positive patients among CD44-low grade positive/negative patients (55.3%) was significantly higher than that among CD44-high grade positive patients(28.6%) (p < 0.05). In the multivariate analysis, the CD44 expression was suggestive of an independent prognostic factor. CONCLUSION: Based on our results for TSIR, Tegafur-uracil may induce apoptosis of tumor cells in patients by the inhibition of thymidylate synthase. It was suggested that CD44 expression could be used as a possible independent predictor of survival. In addition, it was suggested that UFT, via the inhibition of CD44 expression caused the inhibition of distant metastasis.

Tumoral calcium pyrophosphate dihydrate crystal deposition disease. A clinicopathologic analysis of five cases.

We describe five cases of tumoral calcium pyrophosphate dihydrate crystal deposition disease (CPPDCD) and discuss the clinical, radiological and pathological features. Patients included 4 males and 1 female, ranging in age from 49 to 70 years (median, 63 yrs). The wrist was involved in two patients. The thumb, palmar aspect of the proximal phalanx of the middle finger and dorsum of the carpal bone of the hand were involved in one patient each. In one patient, a preoperative diagnosis of chondrosarcoma had been made. Macroscopically, the lesion was a circumscribed whitish-gray mass with a more or less chalky appearance, measuring between 1.0 to 6.2 cm (median, 2.5 cm). Histologically, all five lesions contained areas of calcification with crystal deposits and chondroid metaplasia. The majority of crystals were rhomboid in shape, characteristic of CPPD, but some needle-shaped crystals were also identified, which resembled urate crystals. A review of the 54 reported cases of tumoral CPPDCD including our series indicated that they could be divided into two categories based on anatomic location: central (head and neck) type (n = 33) and distal (extremity) type (n = 21). Patients of these two groups were not different with respect to age and gender, but those with the central type often presented with a painful mass (15 patients, 46%), or neurological disturbances (11 patients, 33%). Patients with the distal type presented with a painless mass or swelling (12 patients, 57%), but none had neurological signs, although 8 (38.1%) presented with acute attack similar to tophaceous gout. Tumoral CP-PDCD should be differentiated from tophaceous gout, tumoral calcinosis, and malignant or benign tumors.

Endoscopic features of villous tumors of the colon: correlation with histological findings.

Data obtained from thirty patients with villous or tubulovillous tumors of the colon were examined in a search for correlations between histological and endoscopic features. There was a good correlation between the two findings. As villous elements became more prominent in the histology, finely granular and/or villous surface patterns, adherent mucus, and a characteristic color (slightly reddish with white spots) were seen more frequently in the endoscopic photographs. These findings are considered to be typical endoscopic features of villous tumor of the colon. Endoscopy using the sprayed dye technique is useful for visualizing the finely granular and/or villous surface pattern.

[Long-term remission of a case of Burkitt's lymphoma accompanied by cardiac tamponade treated by surgical resection and intensive chemotherapy].

A 26-year-old woman was admitted to our hospital because of abdominal mass. She became ileus and an emergency operation was consequently performed. A histological examination of the abdominal tumor indicated proliferation of undifferentiated lymphoblasts with intermingled histiocytes so called "starry sky appearance". The diagnosis was Burkitt's lymphoma. On the 4th post-operative day, a cardiac tamponade became evident. The pericardial effusion contained many lymphoblasts and the diagnosis was pericarditis due to the invasion of lymphoma cells. The pericarditis was successfully treated by infusion of doxycycline into the pericardial space following drainage. The patient responded to systemic chemotherapy with complete remission. 7 courses of systemic chemotherapy along with intrathecal infusions for CNS prophylaxis were subsequently carried out. A state of complete remission has continued for more than 13 months. Cardiac tamponade accompanied by Burkitt's lymphoma is quite rare and has not ever been reported in Japan in our knowledge. The efficacy of surgical treatment before systemic chemotherapy and the series of intrathecal infusions for CNS prophylaxis was demonstrated in this case.

Argyrophil and argentaffin cells in adenomas of the colon and rectum.

The incidence, distribution density and cellular structure of argyrophil and argentaffin cells in 212 colorectal adenomas obtained from 128 colorectums mostly resected surgically were investigated. Out of the 212 adenomas, argyrophil cells and argentaffin cells were found in 162 (76.4%) and 128 (60.4%), respectively. Approximately 10 per cent of adenomas with silver-positive cells showed high distribution densities. There were 128 adenomas in which both argyrophil and argentaffin cells were found. In 33 out of the 128 Paneth's cells and goblet cells were also recognized. The incidence of argyrophil and argentaffin cells tended to become higher in adenomas of the distal colon and the rectum than of the proximal colon, apart from those of the ascending colon. Most of the adenomas with high distribution density of these cells were in the sigmoid colon and rectum, and the distribution pattern was somewhat similar to that of silver-positive cells in the non-neoplastic mucosa. There was no significant difference in the incidence of silver-positive cells among adenomas with different histologic types. Both silver-positive cells were usually found in the lower third portion of the adenomatous glands or tubules, the shape being flask-shaped or cylindrical, and they showed cellular atypicality as the adenoma cells did. It is speculated that silver-positive cells appearing within colorectal adenomas are substantially one of the structural elements of adenomas and are derived from immature adenomatous cells. The present study supports the unitarian theory that neuroendocrine cells in the gastrointestinal mucosa are of endodermal origin.