Takuo Murakami

Epidermal Growth Factor Receptor Overexpression and Genetic Aberrations in Metastatic Squamous-Cell Carcinoma of the Skin

Background: Cutaneous squamous-cell carcinoma (SCC) sometimes causes lymph node metastasis and results in poor prognosis. However, little is known about cytogenetic alterations underlying tumor progression or metastasis. The aim of the present study was to investigate the genetic aberrations and expression of epidermal growth factor receptor (EGFR) in metastatic SCC of the skin. Methods: We undertook comparative genomic hybridization (CGH) analysis of 4 specimens which were obtained from a case of cutaneous SCC, including the primary lesion and 3 lymph nodes of the metastatic lesion. Results: Only one amplified locus (7p12–13) was detected in any metastatic lymph node, in which the EGFR gene is located. Therefore, we applied immunohistochemistry for EGFR to 5 cases of metastatic SCC including the case analyzed using CGH and 4 other cases (5 primary and 5 metastatic lesions). EGFR was expressed in 4 of 5 cases (both primary and metastatic lesions, including the case analyzed using CGH), and the staining patterns of primary and metastatic lesions were different. The primary tumors were focally weakly positive for immunostaining (+), whereas the 4 metastases were diffusely and strongly positive (+++). Conclusions: Our findings suggest that the clone with EGFR expression might selectively metastasize in some cutaneous SCCs. The existence of an EGFR-negative case reveals that EGFR expression is not always required for skin carcinogenesis, but expression of EGFR might confer metastatic potential of cutaneous SCCs.

Intratumoral heterogeneity in DNA ploidy of esophageal squamous cell carcinomas

Intratumoral heterogeneity in DNA ploidy was investigated in 23 cases of squamous cell carcinoma of the esophagus. Nuclear DNA content was determined for multiple samples taken from the same tumor, using a flow cytometric technique. The incidence of DNA aneuploidy was 87% in this series, and DNA indices ranged from 0.78 to 2.64 but most of them fell within values between 1 and 2. Of these cases ten (43.5%) showed intratumoral heterogeneity in DNA ploidy; in addition to a diploid population, one to four heterogeneous aneuploid subpopulations were discernible in the same tumor. However, morphologic variation was minimal within the same tumor. DNA index seen in metastatic lesions was identical with one of those in the primary lesion. Mechanisms responsible for intratumoral difference in DNA ploidy are also discussed from the aspect of tumor progression. Cancer 68:2403–2406, 1991.

Introduction of monoclonal antibodies to bromodeoxyuridine to monitor hepatic regeneration

The effect on the liver of portal vein and/or bile duct branch ligation was examined in rabbits by measuring cellular kinetics using the bromodeoxyuridine labeling index. Twenty-four days after ligation of a portal vein and/or bile duct branch, similar degrees of compensatory regeneration were observed. However, there were significant differences in the pattern in which regeneration developed. Compensatory regeneration after ligation of a bile duct follows a different pattern than that after portal vein branch ligation.

Neurovascular Manipulation for Safer Surgery of Thoracic Esophageal Cancer

We usually perform an antethoracic esophagogastrostomy following subtotal esophagectomy for cancer of the thoracic esophagus due to the simplicity and safety of the operation. However, the incidence rates of anastomotic breakdown and postoperative pulmonary complication are 46.6%–91.0% and 14%–35%, respectively (Fig. 1). Therefore, measures must be taken to make surgical operation of the thoracic esophageal cancer a much safer procedure.

Dilazep, a nucleoside transporter inhibitor, modulates cell cycle progression and DNA synthesis in rat mesangial cells in vitro.

The direct effects of the nucleoside transporter inhibitor dilazep on the cell cycle of mesangial cells have not before been investigated. The purpose of this study was to elucidate whether dilazep can inhibit the proliferation of mesangial cells and how it interferes with the cell cycle of these cells. DNA histograms were used and BrdUrd uptake rate was measured by flow cytometry. There was no significant difference in the cell numbers among the untreated group and the 10−5M, 10−6M or 10−7M dilazep‐treated groups at 24 h of incubation. However, at 48 and 72 h, the cell numbers in the dilazep‐treated groups were significantly lower compared with that of the untreated group (P0.005). The DNA histograms of cultured rat mesangial cells at 12, 24, and 48 h of incubation with 10−5 M dilazep showed that the ratio of the S phase population in the dilazep‐treated group decreased by 2.2% at 12 h, by 9.6% at 24 h, and by 18.9% at 48 h compared with the untreated group. The ratio of the G0/G1 phase population in the dilazep‐treated group significantly increased: 6.8% at 12h (P 0.05), 13.9% at 24 h (P 0.001), and 76.5% at 48 h (P 0.001) compared with the untreated group. A flow cytometric measurement of bivariate DNA/BrdUrd distribution demonstrated that the DNA synthesis rate in the S phase decreased after 6 h (P 0.005) and 12 h (P 0.05) of incubation compared with the untreated group. These results suggest that dilazep inhibits the proliferation of cultured rat mesangial cells by suppressing the G1/S transition by prolonging G2/M and through decreasing the DNA synthesis rate

The surgical management of synchronous hepatocellular carcinoma and thoracic esophageal carcinoma

A 73-year-old man was hospitalized with pathologically documented hepatocellular carcinoma and cirrhosis, and a 5.0-cm tumor located in the left lobe was resected by a left lateral segmentectomy. At the same time, metastatic squamous cell carcinoma was identified by frozen section in a perigastric lymph node in the lesser omentum. Intraoperative endoscopy revealed a 1.0-cm erosive lesion in the thoracic esophagus that was subsequently found to be primary squamous cell carcinoma. Seven weeks later, a transthoracic subtotal esophagectomy with substernal, cervical esophagogastrostomy was performed. Twenty-two months after these resections there has been no recurrence of either the hepatocellular or esophageal carcinomas.

A case of hepatocellular carcinoma with tuberculoma within tumor tissue

We made a diagnosis of hepatocellular carcinoma and performed partial resection of the liver in a 72 year-old woman. Granulomas were observed within hepatocellular carcinoma in the surgical specimen. Microscopic findings demonstrated the granulomas particularly within the tumor, and showed that they were composed of epithelioid cells with caseous necrosis. These tuberculomas compressed the tumor cells, and many lymphocytes had infiltrated the tumor around the tuberculomas. The cancer stage of the patient was early and her prognosis is good.

Clinical Study of Superficial Esophageal Cancer

Esophagectomy was performed in 31 cases of esophageal cancer in our hospital over the past 16 years. We conducted a retrospective study on superficial esophageal cancer concerning treatment and prognosis, and the therapeutic policy based on the depth of invasion was evaluated. As a result, endoscopic mucosectomy or blunt dissection was found to be suitable for cancer which invaded as far as the epithelium. For cancer, which reached the mucosal layer, esophagectomy with level III node dissection should be performed. However, radical esophagectomy with nodal dissection in three areas (cervical, mediastinal, and abdominal), and postoperative adjuvant therapy should be performed for cancer that involves the submucosa.

Effect of Vasoactive Intestinal Polypeptide on the Cardiac Closing Mechanism and Pathophysiology of Achalasia of the Esophagus

Vasoactive intestinal polypeptide (VIP) is a 28 amino acid polypeptide with a close structural and functional relationship to secretin and glucagon [1]. VIP is localized not only in the gastrointestinal tract but also in central and peripheral neurons. We investigated the role of gastrointestinal hormones on the cardiac closing mechanism [2]. In this study, the effects of VIP and secretin were investigated in experimental achalasia dogs and achalasia patients with the manometric method and immunohistochemical technique.

Clinical Results of Improved Surgery for Carcinoma of the Thoracic Esophagus with Lymph Node Metastasis

Despite the development of operative mortality after surgical treatment for carcinoma of the esophagus, the 5-year survival rate for patients who underwent curative resection is still low compared with the finding in other digestive organs. This study was undertaken to analyze the results of our surgical cases, particularly in lymph node metastases for carcinoma in the thoracic esophagus, and reviews briefly our current plan of procedure regarding these patients.