Cyclin D1 is a possible predictor of sensitivity to chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: Chemoradiotherapy is currently performed on patients with advanced esophageal squamous cell carcinoma (SCC). The preoperative administration revealed that the patients who responded well to chemoradiotherapy had favorable outcomes, whereas the poor responders conversely resulted in worse prognosis. The aim of this study was to identify molecular markers predicting sensitivity to chemoradiotherapy prior to this treatment. MATERIALS AND METHODS: Our clinical protocol for chemoradiotherapy for esophageal SCC were enrolled in 34 patients comprising 20 patients who underwent surgery after neoadjuvant chemoradiotherapy and 14 patients who were treated chemoradiotherapy without surgery. The expressions of cyclin D1, p53 and Ki-67 were investigated immunohistochemically in biopsy specimens obtained before the treatment from all 34 patients. The immunoreactivities were compared with responsiveness to chemoradiotherapy as evaluated by macroscopic or microscopic method. RESULTS: The mean rate of primary tumor reduction as estimated by esophagography was 75.3% in the cyclin D1 negative group whereas 42.7% reduction rate was observed in the cyclin D1 positive group. The difference in the reduction rate between cyclin D1 positive and negative groups was statistically significant (p = 0.0025). The immunoreactivities of p53 and Ki-67 did not show a significant correlation with responsiveness to chemoradiotherapy. In neoadjuvant group, patients with cyclin D1-positive tumors showed significantly worse overall survival than patients with cyclin D1-negative tumors (p = 0.0380). CONCLUSIONS: Among 34 patients with esophageal SCC, differences in the responsiveness to chemoradiotherapy were correlated with cyclin D1 immunoreactivity assessed in the biopsy specimens. Thus the cyclin D1 protein may be a useful predictor of sensitivity to concurrent chemoradiotherapy for esophageal SCC.

Laparoscopic splenectomy for a giant splenic epidermoid cyst: report of a case.

The use of laparoscopic splenectomy has increased in recent years, primarily for patients with idiopathic thrombocytopenic purpura (ITP). We describe herein the first known case of a laparoscopic splenectomy to be performed in Japan for a patient with a giant splenic epidermoid cyst. A 26-year-old woman presented to our hospital with the major complaint of a feeling of abdominal fullness. Prior to surgery, an ultrasound-guided splenic cyst puncture was conducted for diagnostic purposes as well as to reduce the size of the cyst. The carbohydrate antigen 19-9 (CA 19-9) level was found to be elevated in the cystic contents and in the serum. Under laparoscopic guidance, the splenic vessels were ligated using a device for extracorporeal ligation, then divided. After the resected spleen had been placed in a retrieval bag, it was delivered out of the abdominal cavity without fragmentation. Following surgery, the patient's serum CA 19-9 level returned to normal. Splenic epidermoid cysts are most often encountered in young women, and laparoscopic surgery to remove cysts of this type is both minimally invasive and excellent from a cosmetic standpoint. Thus, laparoscopic surgery should be considered as the method of choice for the majority of patients diagnosed with a splenic epidermoid cyst.

[A case of advanced gastric carcinoma with disappearance of cancer cells by neoadjuvant chemotherapy].

A 74-year-old man was diagnosed by preoperative X-ray and endoscopy with biopsy as having type 2 advanced gastric carcinoma (poorly differentiated adenocarcinoma) in the antrum. CT scan revealed swelling of the paraaortic lymph nodes, which was considered to be metastasis from the gastric carcinoma. As the cancer was judged to be stage IV and too advanced for a curative surgical resection, a neoadjuvant chemotherapy was initiated. One course of the regimen consisted of 10 mg of CDDP (day 1-5, drip) and 300 mg of UFT (day 1-7, oral), and the patient underwent the regimen three times in succession. After the chemotherapy, the swelling of para-aortic lymph nodes disappeared on CT scan. A distal gastrectomy with D2 lymph nodes dissection and sampling of the para-aortic lymph nodes was performed. Histopathological examination revealed that the cancer cells had completely vanished both in the primary tumor and lymph nodes. The effect of this neoadjuvant chemotherapy was judged to be Grade 3 histopathologically.

Altered microsatellites in incomplete-type intestinal metaplasia adjacent to primary gastric cancers.

AIM: To investigate the presence of genetic instability in precancerous lesions of the stomach. METHODS: Fifteen cases of sporadic gastric cancers with a background of intestinal metaplasia were studied by microsatellite assay at nine loci. Altered metaplastic mucosa was microdissected, reconstructed topographically, and examined immunohistochemically with an anti-p53 antibody, comparing its positive area with foci of microsatellite instability in each individual. RESULTS: Alterations at one or more loci were observed in seven of 15 cancers (46.7%) and four of 15 intestinal metaplasias (26.7%). Two cases of replication error positive phenotype had no microsatellite alterations in their metaplastic mucosa. All the microsatellite alterations in the metaplastic mucosa were restricted to incomplete-type intestinal metaplasia around the respective cancers. Moreover, in one case, an identical pattern of microsatellite alteration was detected in the cancer tissue and in the adjacent metaplastic mucosa, suggesting the sequential development of gastric cancer from intestinal metaplasia. Frequent alteration was found at the locus D1S191 (1q), indicating that this locus might be altered early in the development of intestinal-type gastric cancer. No significant association between microsatellite instability and p53 immunoreactivity was observed in the cases examined. CONCLUSION: These results indicate that microsatellite instability may be an early event in stomach carcinogenesis, especially in intestinal-type cancers.

[Low-dose FP (5-FU+low-dose CDDP) therapy for far advanced upper gastro-intestinal carcinoma].

Low-dose FP therapy was undertaken in 25 patients with far advanced or recurrent carcinoma (13 stomach, 7 esophagus, 3 colon, 1 gallbladder, 1 pancreas). This therapy consisted of intermittent infusion of CDDP (10 mg/body X 5 days) and continuous infusion of 5-FU (500 mg/body X 5 days) for 5 days with 2-day intervals. Patients were treated with at least 2 courses of low-dose FP therapy. Of the 25 patients, 12 with esophageal (7) or gastric (5) carcinoma, in whom curative resection was considered impossible before the operation, were subjected to neoadjuvant chemotherapy. The response rate in the neoadjuvant therapy was 100% (2 disappeared and 5 decreased in size) in the esophageal cancer and 60% (3 decreased in size) in the gastric cancer. But, in 6 patients with esophageal cancer, radiotherapy was combined. In the neoadjuvant cases, pathological effect of Grade 2 was noted in 3 of the 7 esophageal cancers and 1 of the 5 gastric cancers. Of the remaining 13 unresectable patients, a significant improvement of performance status was found in 6 patients. In 19 patients treated with low-dose FP therapy only, leukopenia of Grade 3 was not observed, and there was no nephrotoxicity. Low-dose FP therapy is safe and useful as a neoadjuvant chemotherapy for patients with far advanced esophageal or gastric cancer.

Concurrent amplification of cyclin E and CDK2 genes in colorectal carcinomas.

The genetic changes of cyclin A, DI, E and CDK2 were examined in human colorectal carcinomas by Southern-blot analysis. Gene amplification of cyclin E was detected in 5 of 53 (9.4%) primary colorectal carcinoma tissues. Interestingly, in 3 of 5 tumors showing cyclin E gene amplification, the CDK2 gene was amplified simultaneously with rearrangements. No obvious correlation was detected between gene amplification and clinicopathological features of colorectal carcinomas. Out of 7 colon carcinoma cell lines, 2 showed gene amplification of cyclin E without gene amplification of CDK2. No amplification of cyclin A or DI gene was found in any of the colorectal carcinoma tissues or colon carcinoma cell lines. Our results suggest that the concurrent amplification of cyclin E and CDK2 genes may play a role in colorectal carcinogenesis.

Increased expression and phosphorylation of sh-ptp2 (syp) in human gastric carcinomas.

The expression of SH-PTP2 (SYP), a novel protein tyrosine phosphatase with src homology 2, was examined in human gastric carcinoma cell lines and gastric carcinoma tissues as well as corresponding non-neoplastic mucosas by Northern and Western blotting. The expression of SH-PTP2 mRNA was detected in all 8 gastric carcinoma cell lines at various levels. Most of the cell lines expressed SH-PTP2 protein of 70 kd which corresponds to tyrosine-phosphorylated form, whereas only one cell line expressed unphosphorylated form of SH-PTP2; Fourteen (66.6%) of 21 gastric carcinomas expressed SH-PTP2 mRNA at higher level than non-neoplastic mucosas. Furthermore, most of the gastric carcinomas displayed higher levels of tyrosine-phosphorylated form of SH-PTP2, while non-neoplastic mucosas tended to express unphosphorylated SH-PTP2 protein. These results suggest that the increased expression and tyrosine-phosphorylation of SH-PTP2 may participate in stomach carcinogenesis.

An unusual presentation of spontaneous pneumoperitoneum secondary to the rupture of a gas-containing pyogenic liver abscess: report of a case.

We describe a rare case of spontaneous pneumoperitoneum secondary to the rupture of a gas-containing pyogenic liver abscess in a 59-year-old man. The patient was diagnosed as having a hollow viscus perforation based on a sudden onset of acute abdominal pain along with radiological evidence of bilateral subphrenic feee air (pneumoperitoneum), and underwent an emergency laparotomy. Contrary to expectations, the surgery revealed no perforations of the hollow viscus, but instead a ruptured liver abscess at the dome of the right hepatic lobe was identified associated with suppurative peritonitis. To the best of our knowledge, such a case of spontaneous pneumoperitoneum secondary to the rupture of a gas-containing liver abscess is extremely rare.