Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

Dynamic high-spatial-resolution MR imaging of invasive ductal carcinoma: influence of histological scirrhous component on MR descriptors.

PURPOSE: The purpose of this study was to assess the relationship between the amount of scirrhous component in invasive ductal carcinoma and its MR characteristics. MATERIALS AND METHODS: We retrospectively reviewed 71 consecutive patients with invasive ductal carcinoma smaller than 25 mm (average, 16.6 mm) in diameter. The scirrhous component was defined as invasive foci in small clusters of cancer cells showing desmoplasia. Invasive ductal carcinoma was subclassified into 3 groups in accordance with the amount of the scirrhous component (scirrhous component degree; SCD): SCD I (scirrhous component less than 20%), SCD II (intermediate), and SCD III (more than 80%). Dynamic magnetic resonance (MR) imaging was performed using volumetric interpolated sequence. Prior to dynamic study, T2*-weighted first-pass perfusion images were obtained before, during, and after bolus injection of 0.1 mmol Gd-DTPA/kg. RESULTS: Twenty-eight lesions were classified as SCD I, 14 as SCD II, and 29 as SCD III. Mass margin and signal intensity loss in the perfusion study were significantly different among the 3 SCD groups (P<0.001). The kinetic patterns were significantly different among the 3 SCD groups (P=0.04), and between SCD I/II and SCD III (P=0.03). The presence of enhancing internal septations was significantly different between SCD I/II and SCD III carcinomas (P=0.05). Central enhancement was only observed in SCD I carcinoma (4%; 3/71). CONCLUSION: The histological predominance of the scirrhous component in invasive ductal carcinoma may be one explanation for the differences in morphologic and kinetic patterns on MR imaging.     

Differential mechanisms involved in the anticonflict action of benzodiazepines injected into the central amygdala and mammillary body

The present study was designed to clarify the mechanism of action of benzodiazepines (BDZ) injected into the central amygdala (ACE) and mammillary body (MB). When gamma-aminobutyric acid (GABA) at doses of 30 and 70 micrograms, muscimol (0.01 and 0.03 microgram), valproate (200 micrograms), atropine (20 micrograms) and cyproheptadine (3 micrograms) were bilaterally injected into ACE, a significant and marked increase in the punished responses of conflict schedule was observed. These drugs injected into MB failed to increase the punished responses. In MB, only noradrenaline (NA, 20 micrograms) showed the anticonflict action. NA 20 micrograms also produced the anticonflict action in ACE. These results suggest that the mechanism of anticonflict action of BDZ is different in brain areas. The GABA-ergic, cholinergic, serotonergic and NA-ergic systems seem to be involved in the mechanism of anticonflict action of BDZ in ACE. While the NA-ergic system appears to be operative in MB.     

Basic fibroblast growth factor prevents thalamic degeneration after cortical infarction

In the focal infarction model of the rat middle cerebral artery (MCA), the thalamus of the occluded side becomes gradually atrophic, mainly because of retrograde degeneration. We determined whether basic fibroblast growth factor (bFGF) administered intracisternally could prevent this thalamic atrophy. We occluded the left MCA through a small cranial opening, and animals were then divided into two groups. One group received intracisternal injections of recombinant bFGF (1 microgram dissolved in 0.1 ml of saline with 2% rat serum) starting 1 day after occlusion and repeated once a week to a total dose of 4 micrograms by four injections. The other group received vehicle solution by the same schedule. The animals were perfused and fixed at 28 days after occlusion, and histological examination was made at the level of the caudoputamen and thalamus. In the bFGF-treated rats, the area of the posterior ventral thalamus of the occluded side was 93% of that of the contralateral side, i.e., significantly larger than in the normal saline-treated rats (75%, p less than 0.01). The infarction size was not statistically different in the two groups. Microscopic observation indicated that normal-saline-treated animals showed shrinkage and disappearance of thalamic neurons, whereas bFGF-treated groups showed preservation of thalamic neurons. Computerized analysis of the cell size substantiated this observation. To assess the effect of bFGF on astrocytes, bFGF or vehicle solution was injected into normal rats, and their histology was evaluated at 1, 2, and 4 weeks after injection. The bFGF-injected group showed a significant increase in glial fibrillary acidic protein-positive astrocytes in the brain tissue facing the ventriculocisternal system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of small-bore silastic drains in general thoracic surgery.

STUDY OBJECTIVE: To evaluate the safety and efficacy of small-bore, silastic drains for patients undergoing general thoracic surgery. PATIENTS AND METHODS: Twenty-five patients who received soft, small-bore, silastic drains were compared with 17 patients who received semi-rigid double lumen (DL) tubes retrospectively. RESULTS: The pain score was significantly lower in patients who received the silastic tubes in video-assisted thoracoscopic surgery (VATS) cases on postoperative days 5 and 6 , after continuous epidural analgesia had finished (P=0.018). No specific morbidity was seen in the patients who received silastic tubes. CONCLUSION: We considered that soft, small-bore silastic drains were just as effective as traditional DL tubes, but caused less pain especially in VATS cases.     

Giant cell tumor of the rib

We experienced a rare case of giant cell tumor (GCT) arising in the 5^th rib involving the 5^th vertebral body and transverse process. A 57-year-old man presented with a well-defined mass in the left thoracic cavity on chest x ray examination. Chest computed tomography showed a heterogeneous 7cm-diameter mass originating in the posterior segment of the left 5^th rib. The tumor had spread to the 5^th thoracic vertebra destroying the left half of the body and transverse process. Magnetic resonance imaging showed a heterogeneous-intensity mass involving the 4^th to 6^th ribs. A radical excision of the tumor followed by a 50 Gy radiotherapy was performed after embolization of the feeding arteries. The pathological diagnosis was a GCT. The patient remains well without evidence of recurrence for 6 years following surgery. The present case is only the 14^th case of GCT arising in the rib to have been reported in Japan.     

Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus

BACKGROUND: To understand the immunopathological features of oral lichen planus (OLP), we analyzed the expression of chemokines in the epithelial cell layers. Methods: Epithelia from OLP or healthy gingiva were collected by laser microdissection. The chemokine and chemokine receptor expressions in the epithelia were analyzed by DNA microarray. RESULTS: High levels of MIP-3alpha/LARC/CCL20 and its receptor CCR6 were expressed in the lesional epithelia. Furthermore, DC-CK1/CCL18, ELC/CCL19, SDF-1/CXCL12 and CXCR4 expressions were also increased. Immunohistologial analysis showed that high numbers of Langerhans cells (LCs) were present in the epithelia of OLP. Lesional epithelia also expressed high levels of the ligands specific for CXCR3 (e.g. MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11) and CCR5 (e.g. RANTES/CCL5). CONCLUSIONS: Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells in OLP could be mediated by signaling pathways through CXCR3 and CCR5.     

The participation of adenosine receptors in the adenosine 5''-triphosphate-induced relaxation in the isolated rabbit corpus cavernosum penis

AIM: To investigate the participation of adenosine receptors in the adenosine 5'-triphosphate (ATP)-induced relaxation in the corpus cavernosum penis (CCP) of rabbits. METHODS: The ATP-induced relaxation was assessed on the noradrenaline precontracted CCP of rabbits in the presence and absence of 8-(3-chlorostyryl)caffeine (CSC); an adenosine A(2A) receptor antagonist; alloxazine and MRS1754; adenosine A(2B) receptor antagonists; and ARL67156, an inhibitor of ecto-nucleoside triphosphate diphosphohydrolases. RESULTS: Adenosine and ATP relaxed the noradrenaline precontracted CCP of rabbits in a concentration-dependent manner. The adenosine- and ATP-induced relaxations were suppressed by alloxazine and MRS1754, but not by 8-(3-chlorostyryl)caffeine. ARL67156 potentiated the ATP-induced relaxation but not the adenosine-induced one. MRS1754 suppressed the ATP-induced relaxation potentiated by ARL67156. CONCLUSIONS: The above results suggest that, in the CCP of rabbits, the adenosine receptor mediating adenosine-induced relaxation is of the A(2B) receptor and the ATP directly causes relaxation through the A(2B) receptor on the CCP.     

First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of first-line high-dose chemotherapy (HDCT) combined with peripheral blood stem cell transplantation (PBSCT) for patients with advanced extragonadal germ cell tumors (EGGCT). METHODS: Six male patients with advanced non-seminomatous EGGCT were treated with HDCT combined with PBSCT following 2-3 cycles of conventional-dose induction chemotherapy. The regimens used for HDCT were carboplatin, etoposide and ifosfamide (ICE) in five patients and ICE plus paclitaxel (T-ICE) in one patient, and that for induction therapy was cisplatin, etoposide and bleomycin (PEB) in all patients. As a rule, HDCT was continuously administered until alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin normalized (beta-HCG). RESULTS: Following 1-6 courses of HDCT (median, 4 courses), beta-HCG and AFP were normalized in all patients, and five and one patient were diagnosed as showing partial remission and stable disease, respectively. Five patients underwent surgical resection of residual tumors after HDCT, yielding necrotic tissue in two, mature teratoma in two, and viable cancer tissue in one, and the surgical margin was negative in all patients. At a median follow-up of 36 months, five patients were alive and disease-free, whereas the remaining one died of disease progression. Although all patients had grade 3 hematological toxicity, there was no treatment-related death by combining PBSCT. CONCLUSIONS: First-line HDCT with PBSCT could be safely administered to patients with advanced EGGCT, and the antitumor effect of this treatment was comparatively favorable. First-line HDCT therefore may represent an attractive option for patients with advanced EGGCT.     

Significance of lateral biopsy specimens during transrectal ultrasound-guided prostate biopsies in Japanese men

OBJECTIVES: Lateral biopsies are thought to have a better cancer detection rate compared with standard sextant biopsies. This study aimed to determine whether lateral peripheral zone biopsies in Japanese men who underwent transrectal ultrasound-guided prostate biopsies provided a significantly higher cancer detection rate than sextant biopsies. METHODS: Between 1999 and 2004, data were collected from 461 men who underwent prostate biopsy and had enough data regarding the performance of lateral biopsies for statistical analysis. There were two categories in this study: (i) patients who underwent sextant prostate biopsies; and (ii) patients who underwent sextant biopsies plus lateral biopsies. RESULTS: Prostate cancer was detected in 141 (30.6%) of 461 patients. It was detected in 24 (22.2%) of 108 patients who underwent sextant biopsies and 117 (33.1%) of 353 patients who underwent sextant plus lateral biopsies. Lateral biopsies were not associated with a statistically higher rate of positive biopsy findings; however, we found a significantly higher ratio of patients with positive findings in those with prostate specific antigen (PSA) levels 10 ng/mL (one of 71, 1.4%) among those who had positive cores only in lateral biopsy samples (P < 0.0001). CONCLUSIONS: Lateral biopsies did not show a significantly higher detection ratio of prostate cancer compared to sextant biopsies. However, lateral biopsies were more effective than sextant biopsies in patients with lower PSA levels. Our findings might be useful for the establishment of biopsy strategies to detect prostate cancer, especially in patients with lower PSA levels.