Relationships between Micro-Vascular and Iodine-Staining Patterns in the Vicinity of the Tumor Front of Superficial Esophageal Squamous Carcinoma.

OBJECTIVE: The aim of the present study was to clarify differences between micro-vascular and iodine-staining patterns in the vicinity of the tumor fronts of superficial esophageal squamous cell carcinomas (ESCCs). METHODS: Ten consecutive patients with ESCCs who were treated by endoscopic submucosal dissection (ESD) were enrolled. At the edge of the iodine-unstained area, we observed 183 sites in total using image-enhanced magnifying endoscopy. We classified the micro-vascular and iodine-staining patterns into three types: Type A, in which the line of vascular change matched the border of the iodine-unstained area; Type B, in which the border of the iodine-unstained area extended beyond the line of vascular change; Type C, in which the line of vascular change extended beyond the border of the iodine-unstained area. Then, by examining histopathological sections, we compared the diameter of intra-papillary capillary loops (IPCLs) in cancerous areas and normal squamous epithelium. RESULTS: We investigated 160 sites that the adequate quality of pictures were obtained. There was no case in which the line of vascular change completely matched the whole circumference of the border of an iodine-unstained area. Among the 160 sites, type A was recognized at 76 sites (47.5%), type B at 79 sites (49.4%), and type C at 5 sites (3.1%). Histological examination showed that the mean diameter of the IPCLs in normal squamous epithelium was 16.2±3.7 µm, whereas that of IPCLs in cancerous lesions was 21.0±4.4 µm. CONCLUSIONS: The development of iodine-unstained areas tends to precede any changes in the vascularity of the esophageal surface epithelium.

A pilot trial of S-1 plus irinotecan chemotherapy for esophageal adenocarcinoma.

BACKGROUND/AIMS: This study investigated the clinical efficacy and toxicity of the combination chemotherapy using S-1 plus irinotecan for esophageal adenocarcinoma. METHODOLOGY: This study included 10 patients with histologically confirmed adenocarcinoma of the esophagus or esophagogastric junction between April 2005 and August 2011. S-1 was administered orally at a dose of 80 mg/m²/day from day 1 to 14 and irinotecan was given intravenously on day 1 and 8 at a dose of 80 mg/m². RESULTS: A total of 65 cycles were administered and the response rate was 62.5%. The 50% progression-free survival period and the 50% overall survival period for all of the patients was 8.4 months and 19.1 months, respectively and 5.9 months and 16.3 months for the 8 patients with unresectable or recurrent tumors, respectively. The 2 patients that received adjuvant chemotherapy demonstrated a prophylactic effect for the post-operative recurrence. On the other hand, this therapy showed no severe non-hematological toxicity and only 20% experienced grade 3 neutropenia. As a result, the treatment regimen could generally be performed in an outpatient basis. CONCLUSIONS: The combination chemotherapy using S-1 and irinotecan showed tolerable clinical efficacy in terms of the response rate, survival and toxicity for esophageal adenocarcinoma.

Osteoplastic bone metastasis in esophageal squamous cell cancer: report of a case.

This report presents a case of esophageal squamous cell cancer with osteoplastic bone metastasis. A 58-year-old male patient underwent multimodality treatment for esophageal cancer. Sclerotic changes resembling bone metastasis from prostate cancer were detected in the 4th thoracic and the 5th lumber vertebral body soon after the adjuvant chemoradiotherapy. Systemic examinations revealed no primary cancer as a cause of osteoplastic bone metastasis and no esophageal cancer recurrence. A needle biopsy revealed metastases of esophageal squamous cell cancer with osteoplastic changes. Multiple sclerotic changes were detected in the systemic bones at that time, and new carcinomatous bilateral pleural effusion developed. The drastic systemic progression of the cancer caused the rapid deterioration of the patient's general condition.

Epidermal growth factor receptor is a possible predictor of sensitivity to chemoradiotherapy in the primary lesion of esophageal squamous cell carcinoma.

BACKGROUND: Chemoradiotherapy (CRT) is currently performed for patients with esophageal squamous cell carcinoma (SCC). Some reports have revealed that patients who responded well to CRT had favorable outcomes, whereas poor responders conversely showed a worse prognosis. The aim of this study was to identify molecular markers predicting sensitivity to CRT. METHODS: We reviewed 62 patients with T(3-4), N-any, and M-any esophageal SCC treated with definitive CRT. The regimen comprised protracted 5-fluorouracil infusion and a 2-h infusion of cisplatinum combined with radiation therapy (2 Gy/day) at a total radiation dose of 60 Gy. The expressions of epidermal growth factor receptor (EGFR), vascular endothelial growth factor, cyclin D1, and proliferating cell nuclear antigen were investigated immunohistochemically in biopsy specimens obtained before treatment from all 62 patients. The immunoreactivities were compared with responsiveness to CRT, as evaluated by endoscopy. RESULTS: The complete response rate of the primary tumor estimated by endoscopy was 62% (13/21) in patients in the EGFR-positive group. The difference in the CR rate between EGFR-positive and -negative groups was significant (p = 0.037). The immunoreactivities of the other molecular markers did not show a significant correlation with the responsiveness of the primary lesion to CRT. Multiple logistic regression analysis revealed that positive immunostaining for EGFR was significantly correlated with primary CR for CRT in esophageal SCC. CONCLUSION: Among 62 patients with esophageal SCC, differences in the responsiveness of primary lesions to CRT were correlated with EGFR immunoreactivity assessed in the biopsy specimens. These results suggest that EGFR may help to predict the response of primary sites to definitive CRT in esophageal SCC, although the results should be confirmed in a larger, more homogeneous series.

Evaluation of prognostic factors of esophageal squamous cell carcinoma (stage II-III) after concurrent chemoradiotherapy using biopsy specimens.

BACKGROUND: Recently, attention has been directed to concurrent chemoradiotherapy (CRT) for the treatment of squamous cell carcinoma of the esophagus with regard to efficacy, quality of life and functional preservation, and survival periods comparable to those after standard surgical therapy have been reported in responders to CRT. However, there are some non-responders to CRT, and the prediction of the outcome after CRT is an important subject for future studies. In this study, using biopsy specimens obtained before CRT, we evaluated the relationships between biological markers and the outcome after CRT in order to determine the prognostic factors of CRT. METHODS: The subjects were 51 patients (42 males and nine females: median age 68 years). who were histologically confirmed to have squamous cell carcinoma of the esophagus at stage II or III (UICC). Concurrent CRT consisting of chemotherapy using 5FU and CDDP and radiation therapy (60 Gy) was performed as the initial treatment, and the relationships of overexpression of EGFR, p53, VEGF, PCNA and CyclinD1 were examined immunohistochemically in biopsy specimens collected before treatment. Overall survival was estimated by multivariate analysis. RESULTS: The percentages of patients overexpressing p53, VEGF, PCNA, CyclinD1, and EGFR were 33, 31, 37, 31 and 29%, respectively. On multivariate analysis, T stage (P = 0.0393) and PCNA (P = 0.0302) were found to be significant prognostic factors. CONCLUSIONS: PCNA overexpression appears to be a prognostic factor for squamous cell carcinoma of the esophagus after CRT.

[Weekly administration regimen of paclitaxel (PTX) in patient with inoperable or recurrent gastric cancer].

Paclitaxel is one of the new drugs against advanced/recurrent gastric cancer. We report its efficacy and toxicity with weekly administration for advanced/recurrent gastric cancer. We administered 26 patients (postoperative/non-operation=9/17) PTX 80 mg/m(2)by 1-hour intravenous infusion once a week for 3 weeks followed by one week rest. Median PTX administrations were 2.0 cycles (range:1-22). Characteristics of the patients were median age of 62 (range: 37-78) and PS 0/1/2:2/17/7, male/female:18/8. Over grade 3 toxicities did not occur. The overall response rate was 14.3%, and the non-PD rate was 66.8%. Median time to treatment failure was 61 days and median survival time was 221 days. These results suggest that weekly PTX has modest activity with a favorable toxicity profile in patients with advanced/recurrent gastric cancer, and so this regimen may thus might be recommended in an outpatient treatment setting.

[A case of gastric cancer with multiple liver metastases resistant to TS-1 responding to chemotherapy with paclitaxel plus doxifluridine].

A 74-year-old man was revealed to have type 3 gastric cancer with synchronous multiple liver metastases. Despite treatment with TS-1 (120 mg/body), an increase in tumor size was demonstrated by computer tomography and endoscopy. We tried a course of a combination chemotherapy consisting of paclitaxel (PTX) plus doxifluridine (5'-DFUR ) to reduce the tumor. 5'-DFUR (600 mg/m(2)) was administered day 1 to 14 followed by 7 days'rest as one course. PTX (80 mg/m(2)) was infused on days 1 and 8. After 5 courses, the tumor markers decreased markedly, and computer tomography and endoscopy revealed remarkable tumor reduction which was thought to show a partial response. After 13 courses we discontinued this chemotherapy, so increase of the tumor marker was remarkable. This case suggests that PTX/5'-DFUR protocol is effective for clinical management of gastric cancer resistant to TS-1.

[A case of unresectable hilar cholangiocarcinoma treated with an insertion of biliary stent and herbal medicine obtaining a good quality of life].

An advanced hilar cholangiocarcinoma was poor in prognosis and required a biliary duct drainage tube insertion to prevent jaundice. An endoscopically placed metallic biliary stent is efficient for improving QOL of patients with the disease. This case was of a 65-year-old man. He was admitted to our hospital with obstructive jaundice. Hilar cholangiocarcinoma was diagnosed by computed tomography (CT) and MR cholangiopancreatography (MRCP). Abdominal angiography revealed an unresectable cholangiocarcinoma through the portal vein obstruction and stenosis of the left hepatic artery for tumor invasion. After a second opinion and informed consent, he was inserted a biliary stent (non-covered metallic stent) under an endoscopy. The jaundice was improved further and other laboratory data showed normal results except for tumor markers. After the patient left the hospital, he came to our hospital as an outpatient basis for observation. He was prescribed herbal medicine from the other hospital. Now after ten months since the biliary stent insertion, he has been free from symptoms with normal laboratory data.

[A case of advanced gastric cancer with DIC treated by sequential MTX and 5-FU].

A 75-year-old man was admitted to our hospital complaining of gastric fatigue. Endoscope and CT scan revealed type 3 gastric cancer with paraaortic lymph nodal metastasis. Histological examination of the endoscopic biopsy revealed poorly differentiated adenocarcinoma. A blood examination and bone marrow biopsy revealed DIC causing bone marrow carcinosis. Chemotherapy with sequential therapy consisting of MTX and 5-FU was performed. Stretch of the fold and flatness of the ulcer were obtained against the gastric primary lesion observed endoscopically. Complete response was obtained against the lymph node around the abdominal aorta. Reduction of low back pain and DIC were observed. He was thus able to be discharged and sequential therapy was performed again over 2 months in outpatient care.

Fibroin Gene Transcription in the Embryonic Stages of the Silkworm, Bombyx mori: (fibroin gene/ faithful transcription/ embryonic stages/Bombyx mori).

Using a modified RNase mapping method the transcription of the fibroin gene in Bombyx mori embryos was analyzed. It is known that the silk gland development begins at stage 19 of the 30 embryonic stages and its morphological development completes by stage 25. RNA samples obtained from embryos of a Chinese strain C108 from stages 4 through 23 did not give a positive signal except a faint and transient transcript detected at stage 22. In RNA samples from later stage embryos of a Kanebo commercial strain Kin-Shu X Sho-Wa, a faint and ambiguous fibroin transcript was detected at stages 25 and 26, and a clear and accurate initiation of transcription of the gene was detected from stage 27 and increased greatly at stages 29 and 30 reaching a level of about 0.3 ng/embryo or about 1% of total RNA presumably in the posterior silk gland. These results indicate that the fibroin gene transcription begins for the first time after the completion of the embryonic silk gland development, and also suggest that around stages 25 to 27 are probably a critical time to search for the production and accumulation of a factor(s) governing the transcriptional regulation of the fibroin gene.