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M Tsuneyoshi

Publications and source records attributed to M Tsuneyoshi.

At least 73 records · Page 4Linked to original sources
PubMed1996

The prognostic importance of nuclear morphometry and the MIB-1 index in rhabdomyosarcoma [corrected].

Both nuclear morphometry and an evaluation of the cell proliferative activity have been reported to be useful tools in predicting prognosis in malignant tumors. There have been few reports, however, on rhabdomyosarcoma regarding these evaluative techniques. We performed nuclear morphometry on 51 tumor specimens obtained either by biopsy or by resection of primary and untreated rhabdomyosarcomas, and we then evaluated MIB-1 staining on 25 of the 51 specimens. The morphometric analysis was semiautomatically performed on hematoxylin- and eosin-stained sections by using a personal computer. The areas, perimeters, and lengths of the major and minor axes of the best fitting ellipse of the nuclei were all measured. In addition, the Form Ell (nuclear ellipsoidity score: minor axis/major axis) was calculated. Using the monoclonal MIB-1 antibody, which detects Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, immunohistochemical studies were performed. The values of the major and minor axes and the Form Ell showed significant differences between each histologic subtype whereas the values of nuclear areas did not. We defined the nucleus whose Form ELL was smaller than 0.25 as spindle-shaped nuclei and then divided all cases into two groups on the basis of the ratio of the spindle-shaped nuclei to the total number of nuclei of the tumor cells. The group with the higher ratio showed a significantly better prognosis (P < 0.05). The same trends were also found in the specimens with an embryonal subtype. Nuclear morphometry was a useful tool in predicting prognosis. In particular, the appearance of spindle tumor cells in rhabdomyosarcoma correlated with a better prognosis.

Adolescent↗
PubMed1996

The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver.

We performed immunohistochemical studies on 90 surgically resected liver tumors, including 30 tumors each from hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and metastatic colorectal adenocarcinoma (MCA), using monoclonal antibodies against cytokeratin (CK) 7, CK 19, and CK 20 to examine the differences in the CK expressions in primary and metastatic carcinomas of the liver. We also investigated the usefulness of such expression in the differential diagnosis in addition to existing markers such as alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9. For CK 7, all except for one (97%) of the CCs were diffusely positive, whereas only two (7%) HCCs and one (3%) MCAs were diffusely positive. For CK 19, 23 (77%) CCs and 19 (64%) MCAs were diffusely positive, whereas no HCCs were positive. For CK 20, 22 (74%) MCAs were diffusely positive, whereas no HCC and three (10%) CCs were diffusely positive. The findings concerning the expression of immunohistochemical CK are therefore considered to be useful in addition to the diagnostic criteria when making a differential diagnosis of primary and metastatic carcinomas of the liver.

Adenocarcinoma↗
PubMed1995

A clinicopathologic study of 233 cases with special reference to evaluation with the MIB-1 index.

BACKGROUND: Few articles have analyzed the prognostic data from a large series of primary gastric lymphoma classified according to the concept of mucosa-associated lymphoid tissue (MALT). METHODS: The resected specimens from 233 patients with primary gastric lymphoma were investigated retrospectively, including immunostaining with MIB-1 (Ki-67). RESULTS: Histologically, 70 (30%) of the cases were low grade B-cell lymphoma of MALT, 27 (12%) low grade B-cell lymphoma of MALT with a focal high grade component, 100 (43%) high grade B-cell lymphoma of MALT, 15 (6%) other B-cell lymphomas, 14 (6%) T-cell lymphomas, and 7 (3%) undetermined. Macroscopically, 96 (41%) were superficial-spreading type, 100 (43%) mass-forming, 14 (6%) diffuse-infiltrating, and 23 (10%) unclassified. The MIB-1 index correlated with phenotype, histologic grade, stage, depth of invasion, and macroscopic type. A significantly better survival was noted for young patients, and those with tumors of a B-cell phenotype, histologic low grade, macroscopic superficial-spreading type, low stage, low depth of invasion, and low MIB-1 index. No significantly different survival rates were found between the patients who underwent gastric resection alone and those who also received additional chemotherapy. By Cox multivariate analysis, independent prognosticators included B-cell phenotype, low stage, and macroscopic superficial-spreading type. CONCLUSIONS: In addition to stage, phenotype and macroscopic type are also important prognostic indicators of primary gastric lymphoma. Immunostaining with MIB-1 had limited independent value for predicting prognosis.

Antigens, Nuclear↗
PubMed1995

Osteosarcoma versus malignant fibrous histiocytoma of bone in patients older than 40 years. A clinicopathologic and immunohistochemical analysis with special reference to malignant fibrous histiocytoma-like osteosarcoma.

BACKGROUND: It is often difficult to discriminate between osteosarcoma and malignant fibrous histiocytoma (MFH) of bone, especially in older patients because of the clinical similarities, including the lytic radiologic appearance. A histologic analysis of MFH-like osteosarcoma, which closely resembles MFH of bone both clinically and radiologically, has not yet been conducted thoroughly, and therefore this issue remains controversial. METHODS: Using clinicopathologic and immunohistochemical techniques, the authors studied 24 cases of osteosarcoma arising in patients older than 40 years of age and compared them with 20 cases of MFH of bone from similarly aged patients. RESULTS: Radiography revealed that 68.2% of the osteosarcoma cases were predominantly lytic, whereas all cases of MFH of bone showed either a predominantly or purely lytic pattern. Histologically, osteosarcoma was subclassified as conventional osteoblastic (54.2%), MFH-like (29.2%) containing various amounts of tumor osteoid and/or bone in each of the cases, and conventional fibroblastic (4.2%), whereas all the cases of MFH of bone had a storiform-pleomorphic pattern. Immunohistochemically, no overexpression of p53 protein was found in MFH-like osteosarcoma, whereas it tended to occur more frequently in osteoblastic osteosarcoma (66.7%) and MFH of bone (50.0%). The Ki-67 labeling index was significantly lower in MFH-like osteosarcoma than in MFH of bone. The 5-year survival rate was 18.2% in patients with osteoblastic osteosarcoma, 66.7% in patients with MFH-like osteosarcoma, and 21.5% in patients with MFH of bone. A significant difference in the survival curve was observed between osteoblastic and MFH-like osteosarcoma. CONCLUSIONS: It is proposed that MFH-like osteosarcoma, which shows characteristically different clinical and histologic features from that of conventional osteosarcoma, thus may be considered a variant of osteosarcoma.

Adult↗
PubMed1995

Atypical fibroxanthoma versus benign and malignant fibrous histiocytoma. A comparative study of their proliferative activity using MIB-1, DNA flow cytometry, and p53 immunostaining.

BACKGROUND: MIB-1 was found to be detectable in formalin fixed, paraffin embedded materials with microwave treatment using Ki-67 monoclonal antibody, and immunostaining has been widely documented as a useful marker of proliferation. Because atypical fibroxanthoma (AFX) is regarded as a fibrohistiocytic tumor with an intermediate potential, the proliferative activity of AFX was compared with that of benign and malignant fibrous histiocytomas. METHODS: Thirty-eight soft tissue tumors including atypical fibroxanthoma (n = 5), benign fibrous histiocytoma (FH) (n = 17) and malignant fibrous histiocytoma (MFH) (n = 16) were examined using immunohistochemistry to determine MIB-1, DNA flow cytometry, and p53 (PAb 1801) immunostaining. RESULTS: The mean of the MIB-1 labeling index (MIB-1 LI), defined as the percentage of positive cells for more than 500 cells, was determined in an increasing order as follows: FH, 3.3 +/- 1.8; AFX, 12.2 +/- 6.3; and MFH, 21.5 +/- 10.2. However, the MIB-1 LI of each case in AFX was considerably scattered, and the MIB-1 LI of AFX and MFH overlapped each other. A DNA analysis revealed that the proliferative index (S+G2+M fraction) showed no significant correlation with the MIB-1 LI, and an aneuploid pattern was present in only five (42%) of 12 cases of MFH. p53 positivity was detected in 2 (40%) of 5 cases of AFX and 6 (38%) of 16 cases of MFH. CONCLUSIONS: Although AFX shows a lower degree in the MIB-1 LI than MFH, the MIB-1 LI shows a limited value in relation to the biologic activity of fibrohistiocytic tumors. Aneuploidy demonstrates a malignant potential in fibrohistiocytic tumors.

Adult↗
PubMed1995

Metastasizing intramucosal gastric carcinomas. Well differentiated type and proliferative activity using proliferative cell nuclear antigen and Ki-67.

BACKGROUND: Recently, endoscopic surgery for small superficial gastric carcinomas has become increasingly more challenging, and the treatment criteria remain controversial. METHODS: To examine the metastatic potential of intramucosal gastric cancers (IMGCs), IMGCs with regional lymph node involvement (NI) were compared with IMGCs without regional lymph NI clinicopathologically. To clarify the metastatic behavior of well differentiated adenocarcinoma (W-type), immunohistochemical staining using Ki-67 and proliferating cell nuclear antigen (PCNA) monoclonal antibodies were performed. RESULTS: Of the 943 lesions with IMGC, 21 (2.2%) were NI on histologic examination. There was no significant difference between the macroscopic classification and the incidence of NI. The sizes of the IMGCs with NI (median, 4.3 cm) were significantly larger than the IMGCs without NI (median, 2.4 cm). Among the histologic grades classified according to the predominant features, the incidence of NI in poorly differentiated adenocarcinoma (P-type) (12/304, 3.9%) was significantly higher than that in well differentiated (W-type) (6/489, 1.2%). Besides the 12 P-type IMGCs, 6 well and moderately differentiated type IMGCs contained some poorly differentiated components, totaling 18 IMGCs (86%) that were either mainly or partially P-type. Among the W-type IMGCs, the mean values of the Ki-67 and PCNA labeling indices (LI) for IMGCs with NI (Ki-67, 47.5%; PCNA, 58.3%) were higher than those of the 25 randomly selected IMGCs without NI (Ki-67, 39.2%; PCNA, 39.9%). CONCLUSIONS: The potential for NI in IMGCs seems to be related closely to tumor size, the presence of poorly differentiated components, and, particularly in the W-type IMGC, the LI that are demonstrated immunohistochemically with Ki-67 and/or PCNA.

Adenocarcinoma↗
PubMed1995

Small hepatocellular carcinoma of single nodular type: a specific reference to its surrounding cancerous area undetected radiologically and macroscopically.

A total of 128 surgically resected small hepatocellular carcinomas, measuring less than or equal to 3 cm in diameter, were studied by both macroscopic and histologic examinations. In 95 single nodular-type tumors of the 128 lesions, eight tumors were associated with the cancerous areas of well differentiated hepatocellular carcinoma around the nodule. These surrounding cancerous areas went undetected by both the preoperative radiological examinations and the gross findings of resected specimens. Based on the immunohistochemical findings, the labeling index, both of the proliferating cell nuclear antigen (PCNA) and of the Ki-67 in the surrounding cancerous areas, were lower than that of the main nodules but higher than in the nontumorous liver parenchyma in seven of eight cases. These results suggest that the main nodule was generated from the surrounding cancerous area, supporting the hypothesis of a stepwise progression of HCC. Even if the tumor seems to be a small and single nodular type, it is recommended that its surrounding areas should be closely examined and the surgical cutting margin should be made more than 1.0 cm away from the main nodule at hepatic resection.

Carcinoma, Hepatocellular↗
PubMed1995

Expression of basic fibroblast growth factor and fibroblast growth factor receptor in advanced gastric carcinoma.

The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor (FGFR) mRNA was examined in gastric carcinomas by immunohistochemistry and in situ hybridization, respectively. In the 20 advanced carcinomas examined, bFGF was found in 14 (70.0 per cent) and was confined to the tumour cells, whereas FGFR mRNA was demonstrated in 12 (60.0 per cent) and seen in both tumour cells and endothelial cells. The bFGF and FGFR mRNA-positive carcinomas were larger, were more frequently classified as undifferentiated adenocarcinoma, more frequently invaded the serosal layer, and had a higher rate of lymph node metastases than the bFGF and FGFR mRNA-negative carcinomas. Patients with bFGF and FGFR mRNA-positive carcinomas appear to die earlier than those with bFGF and FGFR mRNA-negative tumours. The values for the carcinomas that were positive for either bFGF or FGFR mRNA fell between these two groups. The findings suggest that the autocrine/paracrine bFGF/FGFR channel is associated with undifferentiated gastric carcinomas and may lead to a poorer prognosis.

Adenocarcinoma↗
PubMed1995

The prognostic significance of lymphovascular space invasion in endometrial cancer when conventional hemotoxylin and eosin staining is compared to immunohistochemical staining.

The current study was undertaken to compare the usefulness of hemotoxylin and eosin (H&E) staining and immunohistochemical staining to identify lymphovascular space invasion (LVSI) in endometrial cancer and to evaluate the presence of LVSI detected by either technique as an independent prognostic factor. Histologic sections from 92 patients with clinical stage I-II endometrial cancer were reviewed, and representative sections were stained immunohistochemically with antibodies for von Willebrand factor and blood group isoantigens. To compare the prognostic significance of LVSI detected by H&E staining with that detected by immunohistochemical staining, univariate and multivariate analyses were performed. Thirty (32.6%) of the 92 cases showed LVSI in H&E staining. In 8 of the 30 cases, LVSI was negative by immunohistochemical staining, while LVSI was positive by immunohistochemical stainings in 2 of 62 cases showing negative LVSI in H&E staining. In univariate analysis, LVSI detected by H&E and immunohistochemical staining was proved to be significant as a prognostic factor. In multivariate analysis by Cox's proportional hazards model, LVSI identified by H&E staining was selected as one of significant prognostic factors, but LVSI identified by immunohistochemical staining not selected. The results of this study indicate that LVSI is one of the independent prognostic factors in endometrial cancer, and that LVSI as detected by H&E is more prognostic of survival than immunohistochemical detection.

Adult↗
PubMed1995

Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma.

BACKGROUND/AIMS: Postoperative intrahepatic recurrence of human hepatocellular carcinoma is high. Recently, the relationship between proliferating cell activity in the cirrhotic liver and occurrence or recurrence of hepatocellular carcinoma has been reported. METHODS: One hundred two resected cases of small hepatocellular carcinoma of < 3 cm in diameter without venous invasion or intrahepatic metastasis were examined to ascertain the factors affecting postoperative intrahepatic recurrence. RESULTS: Cumulative intrahepatic recurrence rates at 1, 3, and 5 years after surgery were 12.0%, 57.2%, and 67.6%, respectively. The log-rank test indicated that serum albumin levels of < 3.7 g/dL, alanine aminotransferase levels of more than 54 IU/L, active inflammation in the nontumorous portion, and high proliferating cell nuclear antigen labeling index in the nontumorous portion (> 23.2%) were significant risk factors for recurrence. Tumor factors, including tumor size, histological grade, or alpha-fetoprotein level, were not significant risk factors. Cox's proportional hazard model identified that serum albumin level and alanine aminotransferase level were independently associated with intrahepatic recurrence after hepatectomy. CONCLUSIONS: This study suggests that the principal cause linked to either a recurrence or a second new growth of hepatocellular carcinoma in the remnant liver after hepatectomy was the state of the underlying liver parenchyma as well as other tumor factors per se.

Adult↗
PubMed1995

Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features.

We herein evaluated 36 cases of combined hepatocellular and cholangiocarcinoma (cHCC-CC) (including 29 surgically resected and seven autopsy cases) by the immunohistochemical methods of anticytokeratin antibodies 7 and 19, and then analyzed the clinicopathologic features by comparing cHCC-CC with ordinary hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The results indicated that even if mucin production could not be confirmed, nine cases with HCC areas that showed a histological resemblance to CC also showed immunohistological biliary differentiation. Therefore, we advocate that these HCC with biliary differentiation based on an immunohistochemical analysis should thus be included in the criteria of cHCC-CC in broad terms. Regardless of the extent of mucin production, the cHCC-CCs as indicated by an immunohistochemical analysis are considered to have a similar background to that of ordinary HCCs regarding such factors as the average age, male:female ratio, hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb) positivity, alpha-fetoprotein level, and the presence of cirrhosis. However, cHCC-CCs tend to metastasize to many organs and the lymph nodes, and, as a result, have a poor prognosis.

Bile Duct Neoplasms↗
PubMed1995

Correlation between metastatic site, histological type, and serum tumor markers of gastric carcinoma.

Gastric carcinoma is classified into intestinal type carcinoma (IC) and diffuse type carcinoma (DC). Intestinal type carcinoma usually tends to metastasize to the liver and DC to the peritoneal cavity. However, discrepant cases are sometimes seen: IC with peritoneal metastasis or DC with liver metastatic site with special reference to these discrepant cases. We also studied the serum tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA] 19-9). We studied 124 autopsied specimens of patients who died of gastric carcinoma. The primary tumors were classified as IC or DC. The discrepant cases included 19 DCs with liver metastasis and 19 ICs with peritoneal dissemination. Most discrepant cases focally had histological features in the primary tumor consistent with our main supposition. On the other hand, discrepant foci were seen only very rarely in the primary tumor of cases with the corresponding usual metastatic site. The serum CEA levels of specimens from cases with liver metastases were higher than those without liver metastases. The serum CA 19-9 levels showed no significant correlation with the metastatic site of the carcinoma. In conclusion, in gastric carcinoma (1) the metastatic site was correlated with histological type (2) even in cases showing a discrepant metastatic site, focal areas of the histological type consistent with our main findings could be found in the primary tumor, and (3) serum CEA levels correlated with liver metastasis.

CA-19-9 Antigen↗
PubMed1995

Cytophotometric study of nuclear DNA content in scirrhous gastric carcinoma.

We made a cytophotometric DNA analysis using 21 scirrhous gastric carcinomas (SGC), and compared the results with those of 12 undifferentiated type early gastric carcinomas (EGC) located in the gastric body. Nuclear DNA content of tumor cells was measured in the mucosa of SGC (SGCm), serosa of SGC (SGCs) and mucosa of EGC (EGCm). DNA distribution pattern was high ploid in 18 SGCm (86%), 16 SGCs (71%) and 4 EGCm (33%). Mean DNA content was 4.02c in SGCm, 3.91c in SGCs and 3.26c in EGCm. Percentage of tumor cells with a DNA content over 3c was 77.4% in SGCm, 69.1% in SGCs and 49.5% in EGCm. Statistically significant differences in these 3 factors were present between SGCm and EGCm, but absent between SGCm and SGCs. Furthermore, DNA distribution pattern was not different between the mucosa and serosa in 19 SGC (90%). The results suggest that most scirrhous gastric carcinomas are high ploid in origin and do not change their biologic behaviour throughout the tumor progression.

Adenocarcinoma, Scirrhous↗
PubMed1995

Intraductal papillary mucinous neoplasms of the pancreas associated with so-called "mucinous ductal ectasia". Histochemical and immunohistochemical analysis of 29 cases.

Twenty-nine patients (20 men, nine women; mean age, 65.9 years; range, 49-77 years) with intraductal papillary mucinous neoplasms associated with so-called "mucinous ductal ectasia" of the pancreas were studied both histochemically and immunohistochemically. These cases included six cases of hyperplasia, 13 adenomas, and 10 adenocarcinomas. The mean sizes of the hyperplasia, adenomas, and adenocarcinomas were 2.0 cm, 3.0 cm, and 4.8 cm in diameter, respectively. Tumor size correlated with the degree of cellular atypia. The proliferative rates were significantly higher in the carcinomatous epithelium with those in the hyperplastic and adenomatous epithelia. The polarity of distribution of carcinoembryonic antigen and carbohydrate antigen 19-9 were better preserved in the hyperplastic epithelia than in the carcinomatous epithelia. On the other hand, the papillary and nonpapillary hyperplastic epithelium contained mainly a neutral periodate-reactive glycoprotein with only trace amounts of sialomucins and sulphomucins. In addition, the adenomatous epithelium contained mostly sialomucins with a small amount of sulphomucins. The carcinomatous epithelium contained predominantly sulphomucin. The results of both the histological and immunohistochemical studies suggested the possibility of a sequential change from nonpapillary and papillary hyperplasia, via adenoma, to carcinoma in intraductal papillary-mucinous neoplasms associated with mucinous ductal ectasia. Moreover, these results, in combination with the histochemical findings, are considered helpful in making an appropriate preoperative diagnosis with endoscopic pancreatic ductal biopsy specimens, thus enabling the surgeon to select the most appropriate surgical procedure.

Adenocarcinoma, Mucinous↗
PubMed1995

An intestinal counterpart of pyogenic granuloma of the skin. A newly proposed entity.

Pyogenic granuloma is a common disease in the skin, but it is extremely rare in the gastrointestinal tract except for the oral cavity. We have seen three lesions (from three patients) of an intestinal counterpart of pyogenic granuloma and have reviewed their clinicopathologic features. Macroscopically, all three lesions revealed a polypoid growth with either a sessile or pedunculated configuration. All had an ulceration on the top. Microscopically, all these lesions were composed of a lobular proliferation of varying sizes of capillaries with an edematous stroma. Endothelial cells of the capillaries were swollen variously and in one case revealed a few mitotic figures. An inflammatory process was associated with the presence of ulcerations. Immunohistochemically, both Factor VIII-related antigen and QB-end/10(CD34) were positive only for the endothelial cells in all three cases. The characteristic macroscopic and histologic features thus allow for an early diagnosis of pyogenic granuloma in the gastrointestinal tract, which is similar to that observed in the skin.

Aged↗
PubMed1995

Small hepatocellular carcinomas undetected on two-phased incremental computed tomography. Angiographic and clinicopathologic findings.

RATIONALE AND OBJECTIVES: To elucidate the characteristic clinicopathologic features of hepatocellular carcinomas (HCCs) undetected on two-phased incremental computed tomography (CT). METHODS: Computed tomographic scans of 115 surgically resected small (< or = 3 cm) HCCs from 83 patients were performed 45 seconds and 6 minutes after the administration of contrast material. These scans were compared with corresponding angiographic and histopathologic findings. RESULTS: Eighty HCCs (70%) were depicted on the early images; 73 (63%) on the delayed images; and 89 (77%) using two-phased incremental CT. The small HCCs undetected on the early images but seen histologically had the following characteristics: (1) absence of a fibrous capsule, (2) well-differentiated tumor, (3) replacing growth patterns of the tumors, (4) lack of fatty metamorphosis and/or clear cell changes, (5) hypovascular on angiography. Those not seen on delayed images had the following characteristics: (1) absence of a fibrous capsule, (2) replacing growth patterns, and (3) presence of portal tracts in the tumors. CONCLUSIONS: The replacing growth pattern and the presence of portal tracts correlate with the undetectability on CT. For HCCs undetected on CT, treatment methods must be considered carefully, because the HCCs may be receiving transsinusoidal and portal blood supplies.

Adult↗
PubMed1995

Adenosquamous carcinoma of the gall-bladder with gastric foveolar-type epithelium.

An 80 year old Japanese man had adenosquamous carcinoma of the gall-bladder characterized by an adenocarcinoma (AC) in the gall-bladder lumen and a squamous cell carcinoma (SCC) in the invaded region of the liver. In the AC, the tumor cells consisted of atypical columnar epithelium with pseudostratification, mimicking gastric foveolar epithelium, while atypical signet-ring cells were scattered within the SCC. There was an abrupt transition between the AC and SCC areas. The tumor cells in the AC area were intensely positive for galactose oxidase-Schiff staining, and paradoxical concanavalin A staining revealed these tumor cells to have Class II mucins. Immunohistochemically, the tumor cells in foveolar-type adenocarcinoma were diffusely positive for cathepsin D. Flow cytometrical analysis of DNA content showed the AC area to be diploid and the SCC area to be aneuploid. The S-phase fraction of the SCC area (46.9%) was larger than that of the AC area (19.5%). The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC area (mean 50.627%) was larger than that of the AC area (mean 3.048%, P < 0.01). These results suggest that the AC area of this tumor, histochemically and immunohistochemically, showed gastric foveolar-type characteristics, the SCC component was squamous cell metaplasia of the pre-existing AC, and that the SCC area had a greater proliferating capacity than the AC area.

Aged↗