Biomedical subjects

Hiroyuki Kuwano

Publications and source records attributed to Hiroyuki Kuwano.

At least 199 records · Page 11Linked to original sources

PubMedDate not supplied

Prognostic value of the expression of Smad6 and Smad7, as inhibitory Smads of the TGF-beta superfamily, in esophageal squamous cell carcinoma.

BACKGROUND: The transforming growth factor beta (TGF-beta) superfamily regulates cell growth in various cells. Previous studies have shown that altered expression of TGF-beta receptors, Smad2 and Smad4, as mediators of TGF-beta superfamily signaling, contributes to tumor progression in esophageal squamous cell carcinoma (SCC). The expression of Smad6 and Smad7 as negative regulators was examined, to investigate the further effects of TGF-B superfamily signaling. MATERIALS AND METHODS: Immunohistochemical staining with anti-Smad6 and anti-Smad7 polyclonal antibodies was performed on surgical specimens obtained from 115 patients with esophageal SCC. RESULTS: The expression of Smad6 and Smad7 was inversely correlated with depth of invasion in the early stages (p = 0.0003 and p = 0.0173, respectively). Moreover, there was a significant correlation between the expression of Smad6 and Smad7, and poor survival rate (p = 0.0078 and p = 0.0207, respectively). CONCLUSION: Smad6 and Smad7 expression affects the progression of early lesions of esophageal SCC and indicates a poor prognosis.

Adult↗

PubMedDate not supplied

The effectiveness of planned esophagectomy after neoadjuvant chemoradiotherapy for advanced esophageal carcinomas.

BACKGROUND: The best treatment option for patients with locally advanced esophageal carcinoma has not yet been determined, especially because the benefits of esophagectomy after neoadjuvant chemoradiotherapy are still controversial. We report the results of a retrospective cohort comparison of definitive chemoradiotherapy without surgery (CRT) versus neoadjuvant chemoradiotherapy followed by planned surgery (CRTS) in patients with advanced esophageal squamous cell carcinoma (SCC). MATERIALS AND METHODS: Between January 1991 and December 2002, 67 patients were enrolled in this study. Fifty of the 67 patients were considered to have inoperable tumors due to distant organ metastasis, distant lymph node metastasis, severe organ dysfunction or rejection of surgery by the patient and received CRT, while the remaining 17 patients were treated with CRTS. The clinical responses of the primary tumors were evaluated. RESULTS: In the 50 CRT patients, the one- and 2-year survival rates were 33.8% and 20.2%, respectively, and the median survival time (MST) was 13.5 months. In the 17 CRTS patients, the response rate (CR + PR) was 76.5%, and the pathological complete response (pCR) rate was 29.4%. Their one- and 2-year survival rates were 61.6% and 35.9%, respectively, and the MST was 24.4 months. The survival rates of the CRT patients were lower than those of the CRTS patients (p = 0.1288). When the 12 patients with distant organ metastases were removed from the CRT group, the one- and 2-year survival rates of the remaining 38 patients were 36.5% and 24.1%, respectively, and the MST was 14.7 months. The survival rates of these 38 CRT patients without distant organ metastases were similar to those of the 12 CRTS patients in the pathological partial response (pPR) group (p = 0.6279). CONCLUSION: This retrospective cohort comparison of CRT versus CRTS demonstrated that there may not be any survival benefit from the addition of surgery in the pPR group for advanced esophageal carcinomas. For patients with a poor response to neoadjuvant chemoradiotherapy, we suggest that the addition of chemoradiotherapy, instead of planned esophagectomy, may show a similar survival rate to definitive CRT. Thus, a large series of a randomized control study will be required to confirm the benefit of surgery after chemoradiotherapy.

Adult↗

PubMedDate not supplied

Loss of KAI1 expression in gastric cancer.

BACKGROUND/AIMS: The purpose of this study was to determine whether the loss of KAI1 expression was related to the clinicopathologic features of patients with gastric cancer. METHODOLOGY: The expression of KAI1 protein was investigated retrospectively in 174 patients with gastric cancer. Immunohistochemical staining of the paraffin sections was performed using polyclonal antibody to KAI1. RESULTS: KAI1 was consistently and highly expressed in normal gastric epithelium, while 47 (27%) of 174 patient samples had KAI1-positive expression in the primary gastric carcinoma. There were no significant differences of age, gender, and tumor location. With regard to the clinicopathological characteristics, significant differences were observed in histological types (p<0.001), increased tumor stage (p<0.001), lymph node (p<0.001) and distant metastasis (p<0.001). KAI1-negative patients had a worse prognosis than that of positive patients in overall survival, but loss of KAI1 expression was not an independent prognostic indicator (p=0.779) by multivariable analysis. CONCLUSIONS: Loss of KAI1 of expression is likely to predict metastasis and poor clinical outcome in gastric cancer patients. For the purpose of predicting the prognosis of gastric cancer patients, it is important to discriminate whether the carcinoma cells have loss of KAI1 expression.

Adenocarcinoma↗

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Esophageal manometric changes and gastroesophageal reflux symptoms after distal gastrectomy for gastric cancer.

BACKGROUND/AIMS: Gastroesophageal reflux is known to be a common complication after gastrectomy. However, its mechanism is not completely understood. We investigated the effects of distal gastrectomy for gastric cancer on the lower esophageal sphincter (LES) and esophageal motility. METHODOLOGY: In 18 patients who underwent distal gastrectomy reconstructed with Billroth I method for gastric cancer, esophageal motility and LES function were evaluated by means of a low-compliance manometric system. The LES pressure was determined by a rapid pull-through technique. Endoscopy before and after operation determined presence or absence of esophagitis and hiatus hernia. RESULTS: No significant differences were observed in esophageal contractile amplitudes before and after distal gastrectomy. After distal gastrectomy, five patients had reflux symptoms of heartburn and regurgitation; 11 had none. Endoscopy revealed esophagitis after distal gastrectomy in two patients with reflux symptoms and one patient without reflux symptoms. The LES pressure in patients with reflux symptoms decreased significantly after distal gastrectomy (before gastrectomy: 26.1 +/- 1.1 mmHg, after distal gastrectomy: 15.3 +/- 3.5 mmHg, p<0.05). There was no significant change in patients without reflux symptoms. CONCLUSIONS: This study demonstrated that LES pressure after distal gastrectomy in patients with reflux symptoms was significantly lower than that before gastrectomy. This result suggested that LES pressure decrease plays an important role in development of gastroesophageal reflux after distal gastrectomy reconstruction with the Billroth I method.

Esophageal Sphincter, Lower↗

PubMedDate not supplied

Mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct.

Mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct has not yet been reported. Much more common than this is secondary involvement of the extrahepatic bile duct in cases of disseminated lymphoma. A 59-year-old man manifesting jaundice was referred to our hospital. PTC revealed an extrahepatic bile duct stenosis from the hilum to the lower part of the choledochus. On the operative specimen, we examined L26/CD20, Bcl-2, UCHL-1/CD45RO, cyclin D1 and p53. Histologically, follicular colonization, centrocyte-like cells and lymphoepithelial lesion was observed. Tumor cells were positive for L26/CD20 and Bcl-2 and were negative for intracytoplasmic immunoglobulins, UCHL-1/CD45RO, cyclin D1 and p53. Pathological diagnosis was mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct. The authors present herein the first case of mucosa-associated lymphoid tissue lymphoma of the extrahepatic bile duct. It was very difficult to distinguish from hilar cholangiocarcinoma clinically. Only incomplete stenosis of the bile duct and 18-F fluoro-2-deoxyglucose positron emission tomography (FDG-PET) could suggest this unusual clinical entity.

Antigens, CD20↗

PubMedDate not supplied

Vascular endothelial growth factor C (VEGF-C) expression in pT2 gastric cancer.

BACKGROUND/AIMS: The purpose of this study was to determine whether the vascular endothelial growth factor C (VEGF-C) protein expression was related to the clinicopathologic features of patients with pT2 (primary tumor invasion of muscularis propria or subserosa) gastric cancer. METHODOLOGY: The expression of VEGF-C protein was investigated retrospectively in 102 patients with pT2 gastric cancer. Immunohistochemical staining of the paraffin sections was performed using a polyclonal antibody to VEGF-C. RESULTS: Normal gastric mucosa was not immunoreactive with an anti-VEGF-C antibody. Among the 102 tumors examined, 27 (26.5%) showed high expression of VEGF-C protein. No staining was observed in the normal tissue surrounding the tumor. There were no significant differences in age, gender, or histological types. With regard to the clinicopathological characteristics, significant differences were observed in depth of tumor invasion (muscularis propria vs. subserosa; p<0.05), lymph node metastasis (p<0.001), and stage grouping (p<0.001). The prognosis for VEGF-C-positive patients was worse than that for VEGF-C-negative patients in terms of overall survival, and VEGF-C expression was an independent prognostic indicator (p=0.023) by multivariable analysis. CONCLUSIONS: Determination of VEGF-C expression is important in predicting nodal metastasis and poor clinical outcome in pT2 gastric cancer patients.

Adult↗

PubMedDate not supplied

Ets-1 expression in gastric cancer.

BACKGROUND/AIMS: Ets-1 protein is a transcription factor that has been implicated in both tumor invasion and neovascularization. The purpose of this study was to investigate the clinical significance of Ets-1 expression in gastric cancer. METHODOLOGY: We examined the expression of Ets-1 protein by immunohistochemical staining in tissues obtained from 124 primary gastric cancers. Ets-1 expression was detected by automated immunodetection (Ventana Medical Systems Inc., Tucon, AZ, USA). RESULTS: Ets-1 was not expressed in normal gastric epithelium. Ets-1 staining was defined as positive in 51.6% (64 of 124) of gastric cancer cases. There were no significant differences in age, gender, or histopathological grading. With regard to clinicopathological characteristics, significant differences were observed in the depth of tumor invasion, lymph node and distant metastases, increased tumor stage, and histological lymphatic and venous invasion. Patients with Ets-1 expression demonstrated poorer survival rates than patients without Ets-1 expression, as determined by the log-rank test (p=0.017), but multivariable analysis showed that the expression of Ets-1 was not an independent prognostic indicator (p=0.370). CONCLUSIONS: Ets-1 expression in gastric cancers is correlated with histological prognostic indicators and is a useful marker for predicting the outcome for patients with gastric cancer.

Adult↗

PubMedDate not supplied

Laparoscopic-assisted partial ileectomy for crohn's disease associated with chronic anemia due to frequent hemorrhage.

Crohn's disease can involve any part of the gastrointestinal tract. Although good conservative treatment is given as soon as possible, most patients with this disease will eventually require surgery. We encountered a case of Crohn's disease associated with anemia which we treated with laparoscopic-assisted ileectomy. The postoperative course was satisfactory. The most important characteristic of Crohn's disease, fat wrapping and extending over the serosal surface toward the antimesenteric border, was observed in the ileum, distinguishing the disease and pinpointing the lesion accurately. This surgical method has an advantage over open surgery in that the recovery time is shorter and incisions are smaller, allowing easier surgery in the future, shortening the patient's hospital stay, and improving the patient's quality of life.

Adult↗

PubMedDate not supplied

Primary squamous cell carcinoma of the stomach: a case report with immunohistochemical and molecular biologic studies.

Primary squamous cell carcinoma (SCC) of the stomach is an extremely rare tumor and its pathogenesis is still unknown. We report a case of SCC of the stomach in a 69-year-old man. The patient's stomach contained an area of SCC surrounded by squamous metaplasia. To our knowledge, this is the first reported study to have investigated the pathogenesis of this tumor type by immunohistochemistry, liquid hybridization assay for human papilloma virus (HPV) infection, and polymerase chain reaction for Epstein-Barr virus (EBV) infection. These tests yielded proof of EBV infection in surgical specimens of the tumor. Therefore, we suggest that EBV infection may be involved in the pathogenesis of SCC arising in the stomach.

Aged↗

PubMedDate not supplied

Gastrointestinal stromal tumor of the stomach: report of a case.

We report herein a case of a 65-year-old woman who had a gastrointestinal stromal tumor (GIST) of the stomach. Preoperative endoscopic and X-ray examinations showed a spherical submucosal tumor in the gastric fornix. We resected the tumor by laparoscopic surgery, because it was detected by computed tomography (CT) and positron emission tomography (PET), and they did not detect distant metastasis. Postoperative histologic examination revealed that the tumor was composed of spindle-shaped cells with elongated nuclei and showed little mitosis. Almost all of the cells showed immunoreactivity for c-kit, CD34, vimentin and but did not show alpha-smooth muscle actin (SMA), S-100, or desmin. The Ki-67 labeling index was 0.8%. The tumor did not show differentiation toward smooth muscle or neural cells. Pathological findings showed this tumor was probably benign. In such cases, careful follow-up is needed to detect liver metastasis and local recurrence.

Aged↗

PubMedDate not supplied

Predictors of response to chemo-radiotherapy and radiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: The sensitivity of tumors to chemotherapy and radiotherapy differs from one case to another and may be influenced by the expression of biological molecules. The presence of six potential predictive markers in esophageal squamous cell carcinoma (ESCC) was investigated and the data obtained were related to the response of the tumors to chemo-radiotherapy and radiotherapy. MATERIALS AND METHODS: Biopsy specimens were obtained from 61 patients with ESCC before treatment with chemo-radiotherapy (31 patients) or radiotherapy (30 patients). External radiotherapy was delivered by a two-field technique to a total of 60-70 Gray. Concurrent chemotherapy consisted of cisplatin or nedaplatin and 5-fluorouracil administered intravenously. The patients were examined before and after treatment by endoscopy, esophagography and computed tomography. The clinical response was classified as effective (> 50% decrease in primary lesion), or ineffective. Immunohistochemical staining for p53, p21, bax, bcl2, heat-shock protein (Hsp) 27 and Hsp70 was performed on the biopsy specimens before therapy. RESULTS: The primary tumor response was effective in 73.8% (45/61) and ineffective in 26.2% (16/61) of patients. Tumors with p53-positive expression were less sensitive than p53-negative tumors (p = 0.033). p21-positive patients (p = 0.027), and Hsp27-negative (p = 0.0057) and Hsp70-negative patients (p = 0.010) were all good responders. Neither bcl2 nor bax expression was related to the efficacy of therapy. Multivariate analysis revealed that Hsp27 was the most reliable predictor of the effect of chemo-radiotherapy and radiotherapy among the four potential markers. p53-negative and Hsp70-negative patients had a more favorable prognosis than p53- and Hsp70-positive patients (p = 0.039, p = 0.038, respectively). CONCLUSION: Expression of Hsp27 was a good predictor of the response of ESCC to chemo-radiotherapy and radiotherapy.

Adult↗

PubMedDate not supplied

Serum p53 antibodies in drainage blood from the azygos vein in patients with esophageal carcinoma.

BACKGROUND: Serum p53 antibodies (p53-Ab) have been detected in some cancers. The possible correlation between serum p53-Ab levels in drainage blood from the azygos vein in patients with esophageal carcinoma and prognosis was investigated. MATERIALS AND METHODS: Serum p53-Ab levels were examined in both the peripheral and azygos veins of 57 patients, and in the peripheral vein of 17 healthy volunteers. Serum p53-Ab levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The positive rate of serum p53-Ab in the peripheral vein of the patients was 31.6%, significantly higher than that of the normal volunteers. There were no significant correlations between the clinicopathological features and the serum p53-Ab in either the peripheral or azygos veins. Serum p53-Ab levels in either vein did not correlate with prognosis in the univariate survival analysis, although the levels in the two veins were significantly correlated. CONCLUSION: Serum p53-Ab levels in the azygos vein did not reflect the tumor status or prognosis more directly or accurately than those in the peripheral vein, since levels in the two veins were similar. Therefore, measurement of serum p53-Ab in the azygos vein does not appear to be necessary.

Antibodies, Neoplasm↗

PubMedDate not supplied

Classification of recurrent esophageal cancer after radical esophagectomy with two- or three-field lymphadenectomy.

BACKGROUND: Although patients with recurrent diseases have a very poor prognosis, appropriate pretreatment classification for management of recurrent esophageal cancers has yet to be identified. The patterns of recurrence following radial esophagectomy were retrospectively assessed, and evaluated for possible adaptation as a novel classification of recurrent esophageal cancer. PATIENTS AND METHODS: One hundred and sixty thoracic esophageal cancer patients (142 men; 18 women), who underwent radical esophagectomy without preoperative treatment, were studied. RESULTS: Recurrence occurred in 59 (36.8%) patients. The relationship between recurrence and clinicopathological features revealed significant associations between recurrence and age at surgery (p<0.05), tumor (p<0.0001), lymph node (p<0.0001) and metastatic status (p<0.01), pathological stage (p<0.0001) and lymph node dissection (p<0.0001). Locoregional recurrence occurred in 13 (22%) patients, distant in 30 (51%) and mixed in 16 (27%). Mixed recurrence occurred the fastest and showed the poorest prognosis. A novel classification for recurrent esophageal cancer was proposed based on the clinical findings. Univariate analysis of the prognostic factors for post-recurrent survival revealed a significant association with distant organ recurrence (p<0.05). CONCLUSION: Mixed recurrence had a poorer outcome than other recurrences. The proposed classification of clinical findings for recurrent esophageal cancer was shown to be useful; however, further studies with a larger number of recurrent esophageal cancers are required for stage grouping of the proposed classification.

Adult↗

PubMedDate not supplied

Expression of p53 in esophageal carcinoma with multiple areas unstained by iodine.

BACKGROUND/AIMS: Esophageal squamous cell carcinoma is occasionally associated with multiple areas in the surrounding mucosa unstained with iodine. METHODOLOGY: We examined 21 male patients with superficial esophageal carcinoma. Group 1 consisted of 4 cases of superficial esophageal carcinoma associated with multiple lesions that did not stain with iodine. Group 2 comprised 17 cases of a solitary tumor without major additional lesions in the mucosa. We assessed the correlation between clinicopathological factors, a history of tobacco and alcohol consumption, and p53 expression in the two groups. RESULTS: We found four cases (group 1) of superficial esophageal squamous cell carcinoma where there were a total of 10 satellite tumors in addition to the main tumor. These patients tended to have a higher daily consumption of tobacco and alcohol than those in group 2. Moreover in all these group 1 cases there was intraepithelial spread of the tumors and p53 overexpression in all of the main and additional tumors. CONCLUSIONS: We have found that higher tobacco and alcohol consumption are closely related to multiple lesions unstained by iodine and abnormal expression of the p53 gene.

Adult↗

PubMedDate not supplied

Evaluation of tumor malignancy in esophageal squamous cell carcinoma using different characteristic factors.

BACKGROUND: We have been investigating various molecules correlated with the malignancy of esophageal squamous cell carcinoma and, in the present study, we examined the correlation of four of them (KAI1, FAK, EphA2, Ki-67 labeling index) with the prognosis of affected patients. Furthermore, the use of biopsy samples was studied to evaluate whether the grade of tumor malignancy can be determined before treatment in a clinical setting. MATERIALS AND METHODS: Tissue specimens that had been surgically removed from 91 patients with thoracic esophageal cancer and 247 biopsy samples were examined. The malignancy index (MI) was defined in terms of the KAI1, FAK and EphA2 scores and the Ki-67 labeling index, and the reliability and utility of the correlation between MI and prognosis was evaluated. RESULTS: The mean 5-year survival rate of patients with MI=0 was 100%, while that of patients with MI=1, 2 and 3 was 70%, 48% and 10%, respectively. Patients with MI=4 all died, with the exception of one who has been observed for 3 years. The rate of concordance between the biopsy samples and surgical specimens was 79.4% for KAI1, 88.2% for FAK and 73.5% for EphA2, and the rates of concordance for 1, 2, 3, 4, 5, 6, 7 and 8 biopsy samples were 66.7%, 64.1%, 74.5%, 90.7%, 91.7%, 83.3%, 100% and 100%, respectively. CONCLUSION: It may be feasible to evaluate the malignancy of tumor cells and to predict patient outcome by using multiple marker molecules. It is anticipated that such data will accelerate the development of "tailor-made" therapy.

Adult↗

PubMedDate not supplied

Comparison between whole-body positron emission tomography and bone scintigraphy in evaluating bony metastases of esophageal carcinomas.

BACKGROUND: Positron emission tomography (PET) with 18-F-fluorodeoxyglucose (FDG) has already proved useful in assessing the extension of esophageal carcinomas, detecting tumor recurrence and monitoring responses to therapy. This study aimed to elucidate the potential role of FDG-PET compared with technetium-99m methylene diphosphonate (Tc-99m MDP) bone scintigraphy in the evaluation of bony metastasis in esophageal carcinoma patients. PATIENTS AND METHODS: Forty-four patients with thoracic esophageal carcinomas, who underwent FDG-PET together with bone scintigraphy within 1 month between January 2000 and September 2003, were included in this study. RESULTS: Of the 44 patients, 13 had 31 bone metastases and, of these, 6 were diagnosed pretreatment and 7 had recurrence after esophagectomy surgery. Of the 31 metastases, 9 were in the vertebral column, 11 in the thoracic cage (including the ribs, clavicle, sternum and scapula), 9 in the pelvic bones and 2 in the long bones of the extremities. In evaluating the detection of bony metastasis, FDG-PET showed 92% sensitivity, 94% specificity and 93% accuracy, compared with 77%, 84% and 82%o, respectively, for bone scintigraphy. Although the sensitivity, specificity and accuracy of PET were slightly higher than those of bone scintigraphy, these differences were not statistically significant according to the McNemar's test. Three patients with false-negative findings on their bone scans had positive findings with PET; all of these lesions were osteolytic metastases. CONCLUSION: FDG-PET scans were superior to bone scintigraphy in detecting bony metastases of esophageal carcinomas. Therefore, FDG-PET can be used for the detection and follow-up of bone tumors when Tc-99m MDP bone scintigraphy gives negative findings.

Adult↗

PubMedDate not supplied

Clinical factors influencing CT findings in patients with acute appendicitis.

BACKGROUND/AIMS: CT has proven useful in diagnosing appendicitis, but it also has some disadvantages. In this study we investigated clinical factors influencing CT findings of acute appendicitis and identified the most appropriate patients for preoperative CT. METHODOLOGY: Enhanced helical CT scans were obtained preoperatively in 95 patients who underwent appendectomy. They were gangrenous in 52 (55%), phlegmonous in 38 (40%) and catarrhal in 5 (5%) and we usually indicated emergent surgery for phlegmonous or gangrenous appendicitis patients. 62 (69%) of 90 phlegmonous or gangrenous cases had both an enlarged appendix (> or = 6mm) and periappendiceal fat strand in CT, which strongly suggested the need for emergent operation (Positive group). We compared clinical factors in the positive group with those in the other 28 patients (Equivocal group). RESULTS: There was no significant difference between the positive and equivocal groups in age, gender, or white blood cell count. The depth of subcutaneous fat (SCF) at the umbilicus level in CT and the number of patients with gangrenous appendicitis were significantly increased in the positive group compared with the equivocal group by both univariate and multilogistic regression analysis. CONCLUSIONS: These indicated that the degree of inflammation and SCF were significantly associated with CT findings of appendicitis and CT should be routinely done in obese patients.

Acute Disease↗

PubMedDate not supplied

Second-line combination chemotherapy of oral S-1 with cisplatin and irinotecan for colorectal cancer resistant to 5-FU.

BACKGROUND/AIMS: A phase I clinical trial has been planned to determine the recommended dose and to assess the safety and efficacy of combination chemotherapy of S-1 with cisplatin and irinotecan (SCI regimen) as a second-line treatment in 5-fluorouracil (5-FU) resistant colorectal cancer (CRC). METHODOLOGY: Patients with unresectable recurrent or metastatic CRC were enrolled in this study for second-line treatment. On an outpatient basis, the patients received a treatment SCI regimen comprising S-1 oral administration for 28 days followed by withdrawal for 2 weeks, plus cisplatin and irinotecan were administered on days 1, 8, 15 and 22 by intravenous injection. These courses were repeated every 6 weeks. Starting doses were 70 mg/m2 S-1, 6 mg/m2 Cisplatin, and 60 mg/m2 Irinotecan. RESULTS: A total of 29 patients was enrolled. Dose-limiting toxicities were fatigue, nausea, and leucopenia. Twenty-three patients at recommended dose were evaluable for treatment response. The response rate was 21.7% (5 partial responses, 13 stable diseases, and 5 progressive diseases). The median progression-free survival rate was 4.3 months; the median survival time was 9.6 months. CONCLUSIONS: The SCI regimen is feasible in an outpatient setting and should be considered as second-line chemotherapy for patients with 5-FU resistant CRC.

Administration, Oral↗