An oral anticancer drug, TS-1, enabled a patient with advanced gastric cancer with Virchow's metastasis to receive curative resection

We encountered a patient with advanced gastric cancer, with Virchow's lymph node metastasis, who subsequently underwent curative resection after neoadjuvant chemotherapy with the newly developed oral anticancer drug, TS-1. The patient was a 67-year-old woman who had a type 2 tumor in the middle third of the stomach, and Virchow's lymph node metastasis, which was diagnosed by fine-needle aspiration cytology; she also had swollen paraaortic lymph nodes. Curative resection was considered impossible, and TS-1 (100 mg/day) was administered for 28 days in one course, mainly in the outpatient clinic. Although grade 2 stomatitis interrupted the therapy on day 21 of the second course and on day 7 of the third course, the type 2 tumor showed marked remission (partial response; PR) and the metastasis in the Virchow's and paraaortic lymph nodes had completely disappeared after the third course (complete response; CR). Eleven weeks after the completion of the TS-1 treatment, total gastric resection with D3 lymph node dissection was performed. Histopathological examination revealed tumor involvement only in the mucosal and submucosal layers of the stomach and the no. 4d lymph node. Most of the tumor was replaced with fibrosis with granulomatous change in the muscularis propria of the stomach and in the no. 3, no. 6, and no. 7 lymph nodes. This may be the first report of a patient with advanced gastric cancer with Virchow's lymph node metastasis who successfully received curative resection following neoadjuvant chemotherapy with a single oral anticancer drug. Received: August 7, 2001 / Accepted: January 28, 2002     

Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104.

PURPOSE: To evaluate the optimal timing for thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study Group of the Japan Clinical Oncology Group conducted a phase III study in which patients were randomized to sequential TRT or concurrent TRT. PATIENTS AND METHODS: We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. RESULTS: Concurrent radiotherapy yielded better survival than sequential radiotherapy (P =.097 by log-rank test). The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm. CONCLUSION: This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.     

Two cases of advanced gastric cancer, successfully treated with TS-1/CDDP combination chemotherapy--case report

We reported 2 cases with advanced gastric cancer, successfully treated with TS-1 and CDDP. Case 1 had Type 3 gastric cancer with left supra-clavicular (Virchow) and para-aortic lymph node metastases. Those distant node metastases completely disappeared after two courses of neoadjuvant chemotherapy (NAC) consisting of TS-1/ CDDP, and radical surgery for cure was conducted. The second case had Type 3 carcinoma with peritoneal dissemination. The primary lesion significantly decreased after four courses of the combination chemotherapy. The patient has been alive for 1 year and a half after 14 courses of TS-1/CDDP with stable disease. Significance of TS-1/CDDP in far advanced gastric cancer was discussed.     

Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction

Osteopontin has been reported to have an important role in cardiac fibrosis. However, little is known about the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blockers (ARB) on osteopontin expression in infarcted myocardium. The purpose of this study was to elucidate the effects of an ACEI (perindpril) and an ARB (candesartan cilexitil) on cardiac function as assessed by Doppler echocardiography and cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted rats. ACEI or ARB was administered after myocardial infarction (MI). At 4 weeks after MI, cardiac function, and mRNAs in non-infarcted myocardium were analyzed. ACEI and ARB equally prevented left ventricular dilatation, reduction of ejection fraction, and the increase in E/A wave velocity ratio and the rate of E wave deceleration by MI. ACEI and ARB significantly suppressed increased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, osteopontin, and collagen I and III in the non-infarcted ventricle at 4 weeks. Immunohistochemically stained osteopontin was increased in interstitial fibrosis of non-infarcted myocardium. Both ACEI and ARB significantly prevented cardiac fibrosis and osteopontin expression. In conclusion, angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium and prevents cardiac remodeling after MI.     

Metastatic tumor of spermatic cord with elevation of serum human chorionic gonadotropin beta-subunit

A 62-year-old man was presented with a firm mass in right scrotum. Serum LDH and AFP were within normal range, but hCG-beta was elevated (2.3 ng/ml). Under the diagnosis of right testicular tumor, he underwent right radical orchiectomy. The specimen was a spermatic cord tumor with poorly differentiated adenocarcinoma. hCG-beta was still elevated postoperatively and gastric fiber revealed adenocarcinoma of the stomach. Histochemical staining for hCG-beta was positive in both tumor of the spermatic cord and stomach. Finally the tumor was diagnosed as metastatic tumor of spermatic cord from gastric cancer, causing the elevation of hCG-beta.     

Improvement of oligoasthenozoospermia in epileptic patients on switching anti-epilepsy medication from sodium valproate to phenytoin

We present two cases of infertile male patients with oligoasthenozoospermia who were receiving anti-epilepsy medication. Complete reversal of the spermatic dysfunction followed by a successful conception was achieved after discontinuation of sodium valproate, suggesting that the drug was responsible for spermatic dysfunction in these individuals.     

Gastropleural fistula due to gastric perforation after lobectomy for lung cancer

We report a case of acute gastropleural fistula due to gastric perforation after a left lower lobectomy for lung cancer. A 76-year-old male, who received a left hemicolectomy 20 years previously, came to our hospital for surgical treatment of lung cancer, which was performed uneventfully as a left lower lobectomy with combined resection of the diaphragm. On the postoperative day 2, acute dilatation of the stomach followed by gradual cardiopulmonary collapse, and then gastric perforation into the thorax occurred. The perforated stomach wall and diaphragm became paper-thin and necrotic, though the abdominal cavity was free of contamination. This life-threatening condition was treated by an emergency thoracotomy and partial gastrectomy through the thorax, as the left hemidiaphragm was remarkably elevated. An oeganoaxial torsion gastric volvulus caused by anatomic rotation following the lobectomy was speculated as the disease process, with loss of suspended tissue of the gastro-colic ligament from the left hemicolectomy being a possible predisposing factor. Such an episode is rare, however, it should be looked for during perioperative care following a lobectomy.     

Late outcomes after isolated coronary artery bypass grafting for ischemic mitral regurgitation

Objectives: Although ischemic mitral regurgitation (IMR) is one of the most important issues to determine therapeutic strategy for ischemic heart disease, long-term outcome after coronary artery bypass grafting (CABG) for IMR is still unclear. It is also controversial how patients who would benefit from mitral valve (MV) surgery in combination with CABG should be identified. The purpose of this study is to elucidate late outcomes after isolated CABG for moderate IMR and to assess the indication of combined MV surgery. Methods: Two hundred and seventy-nine patients who had grade 2 or 3 IMR preoperatively and underwent isolated CABG between 1980 and 2002 in our institute were enrolled. Mitral regurgitation was assessed by 2-dimensional Doppler echocardiography and left ventriculography. Among them, 84 patients (30.1%) had left ventricular ejection fraction (LVEF) less than 30% and 186 patients (66.7%) had prior inferior myocardial infarction (MI). Results: One hundred and twenty-nine patients (46.2%) remained grade 2 or greater MR early postoperatively. Actuarial survival and freedom from cardiac events, analyzed by the Kaplan-Meier method, were 90.9% and 87.7% at 1 year, 79.2% and 68.8% at 5 years, 54.9% and 49.1% at 10 years and 48.8% and 18.9% at 15 years. Independent predictive risk factors for cardiac events, analyzed by multivariate analysis using the Cox proportional hazard model, were grade 2 or greater MR which remained early postoperatively (p=0.0002), LVEF<30% preoperatively (p=0.0006), no inferior MI preoperatively (p=0.007) and no internal thoracic artery-left anterior descending artery graft (p=0.049). More than a 15% decrease in LVEF at more than 3 years after the operation was seen despite patent bypass grafts in 17.2% of patients who received a late follow-up catheterization, although 41.4% of patients showed an increase or less than 5% decrease in LVEF during this period. Conclusion: Combined MV surgery with CABG for IMR should be considered in patients with poor LVEF or without prior inferior MI.     

Glomerular plasmin-like activity in relation to nephritis-associated plasmin receptor in acute poststreptococcal glomerulonephritis

A nephritogenic antigen for acute poststreptococcal glomerulonephritis (APSGN) was isolated recently from group A streptococcus and termed nephritis-associated plasmin receptor (NAPlr). In vitro experimental data indicate that the pathogenic role of NAPlr occurs through its ability to bind to plasmin and maintain its proteolytic activity. However, the mechanism whereby this antigen induces glomerular damage in vivo has not been fully elucidated. Renal biopsy tissues from 17 patients with APSGN, 8 patients with rapidly progressive glomerulonephritis, and 10 normal kidneys were analyzed in this study. Plasmin-like activity was assessed on cryostat sections by in situ zymography with a plasmin-sensitive synthetic substrate. Serial sections were simultaneously assessed for NAPlr deposition by immunofluorescence staining. Glomerular plasmin-like activity was absent or weak in normal controls and in patients with rapidly progressive glomerulonephritis, although tubulointerstitial activity was occasionally detected. Prominent glomerular plasmin-like activity was found in patients who had APSGN and in whom glomerular NAPlr was positive, whereas it was absent or weak in patients who had APSGN and in whom glomerular NAPlr was negative. The distribution of glomerular plasmin-like activity was identical to that of NAPlr deposition but was generally different from that of fibrin(ogen) deposition as assessed by double staining. The activity was abolished by the addition of aprotinin to the reaction mixture but was not altered by the addition of a matrix metalloprotease inhibitor, a cysteine protease inhibitor, or inhibitors of plasminogen activators. Thus, upregulated glomerular plasmin-like activity in relation to NAPlr deposition in APSGN was identified. This result supports the nephritogenic character of NAPlr and offers insight into the mechanism whereby this antigen induces nephritis.