Yoshinori Shitara

Alterations of p73 preferentially occur in gastric adenocarcinomas with foveolar epithelial phenotype.

To establish the possible involvement of p73, a newly discovered p53‐related candidate as a tumor‐suppressor gene in human stomach carcinogenesis, the allelic status, allele‐specific expression and mutations of the gene were investigated using PCR–restriction fragment length polymorphism (PCR‐RFLP) analysis, RT‐PCR SSCP analysis and direct DNA sequencing in 95 gastric adenocarcinomas. Of these, 32 exhibited the heterozygous p73 allele for the StyI restriction site in exon 2. Among these, the cancer DNA of 12 revealed loss of heterozygosity (LOH) of p73. All of the cancers with p73 LOH exhibited phenotypes of foveolar epithelium of the stomach. RT‐PCR SSCP analysis of p73 heterozygous cases demonstrated not only bi‐allelic expression of the gene but also relatively reduced expression of the affected allele in 6 of 8 tumors with p73 LOH. No gene mutation was detected in the remaining allele of LOH‐positive cancers. Our results suggest that alterations of p73, including LOH and abnormal expression, may play roles in the genesis of foveolar‐type gastric adenocarcinomas, though this is not in line with a classical Knudsons “2‐hit” model. Int. J. Cancer 83:192–196, 1999.

Impact of preexisting pulmonary fibrosis detected on chest radiograph and CT on the development of gefitinib-related interstitial lung disease.

Objectives:Although preexisting pulmonary fibrosis (PF) on chest radiograph is known to be a risk factor of gefitinib-related interstitial lung disease (ILD), the significance of PF detected by chest computed tomography (CT) on the development of gefitinib-related ILD has not been investigated sufficiently. Methods:We reviewed 182 nonsmall cell lung cancer patients treated with gefitinib between July 2002 and March 2003. Chest radiographs and CT were taken in all patients periodically and reviewed by radiologists. PF was defined as ground-glass attenuation, consolidation, or reticular shadow without segmental distribution. Gefitinib-related ILD was defined as the acute respiratory failure developed during the course of gefitinib administration and lack of evidence for other cause of respiratory failure. Expected risk factors for gefitinib-related ILD were evaluated in multivariate analysis. Results:There were 15 patients with PF. Nine PF were detected on both chest radiograph and chest CT, and 6 on only chest CT. Twelve patients (6.6%) developed ILD during the course of gefitinib monotherapy and 4 died of it. Univariate and multivariate analyses showed that PF detected on chest radiograph was found to be the only significant risk factor for developing ILD (32.2, P < 0.001). Preexisting fibrosis diagnosed on chest CT but not apparent on chest radiograph was not significantly correlated with ILD. Conclusion:Gefitinib should not be given to patients with PF apparent on chest radiograph. Patients with PF on chest CT but not detected on chest radiograph could be treated carefully with gefitinib, but a risk-benefit analysis should be considered.

Rosai-Dorfman disease of the colon presented as small solitary polypoid lesion

Rosai-Dorfman disease (RDD) was formerly known as “sinus histiocytosis with massive lymphadenopathy”, and cases involving the gastrointestinal tract are rare. We present a case of pure extranodal RDD, resected as a polypoid lesion in colonoscopic study. The patient was a 62-year old woman with a history of sigmoidectomy for unexplained peritonitis. Microscopic study of the polypoid lesion showed the submucosal mass with histological and immunological features of RDD. The whole body computed tomography revealed neither lymphadenopathy nor tumor-like mass.

Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report.

Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT)/calcium folinate (leucovorin, LV) was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX) were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy.

A case report of intracholecystic papillary neoplasm of the gallbladder resembling a submucosal tumor

BackgroundIntracholecystic papillary neoplasm (ICPN) is defined as papillary tumors detected macroscopically in the gallbladder. We report a case of ICPN which exhibited the atypical form like a submucosal tumor.Case presentationA 70-year-old man was admitted to our hospital because of hepatic disorder. Computed tomography and magnetic resonance imaging showed irregular thickening of the wall within the gallbladder fundus. Because the lesion might have been malignant, we performed laparoscopic cholecystectomy and liver bed resection. Macroscopic findings showed the mucosal surface of the tumor was smooth, and its form was similar to that of a submucosal tumor. Histopathological examination revealed papillary tumors within the mass with low-grade dysplasia; therefore, we diagnosed ICPN.ConclusionIn the present case, ICPN was resembling a submucosal tumor macroscopically because the tumors arose into the Rokitansky-Aschoff sinus and the adenomyomatous hyperplasia was merged with the ICPN. It is necessary to consider the possibility of tumor lesions within adenomyomatous hyperplasia.

Expression of amino acid transporter (LAT1 and 4F2hc) in pulmonary pleomorphic carcinoma

Amino acid transporters are necessary for tumor growth, metastasis, and survival of various neoplasms; however, the clinicopathological significance of L-type amino acid transporter 1 (LAT1) and 4F2 cell surface antigen (4F2hc) in patients with pulmonary pleomorphic carcinoma (PPC) remainsunknown. The aim of this study is to clarify the prognostic impact of these amino acid transporters in PPC. One hundred five patients with surgically resected PPC were assessed by immunohistochemistry. The expression of LAT1 and 4F2hc, and Ki-67 labeling index were investigated using specimens of the resected tumors. LAT1 and 4F2hc were highly expressed in 35% and 53% of all patients (n = 105, P < .01), 25% and 48% of patients with an adenocarcinoma component (n = 48, P = .02), and 44% and 58% of patients with a nonadenocarcinoma component (n = 57, P = .18), respectively. A high LAT1 expression was significantly related to advanced disease, lymphatic permeation, tumor cell proliferation, and 4F2hc expression. By multivariate analysis, LAT1 and 4F2hc were identified as significant independent markers for predicting a worse prognosis. LAT1 is highly expressed in PPC, and high LAT1 expression can serve as a significant predictor linked to a worse prognosis in patients with PPC.

Successful surgical treatment of a spontaneous rupture of the esophagus diagnosed two days after onset.

Esophageal perforation is a relatively uncommon disease with a high rate of mortality and morbidity. Delay in the diagnosis and treatment occurs in more than 50% of cases, leading to a mortality rate of 40–60%. Primary repair is generally considered the gold standard for patients who present within the first 24 h following perforation of the esophagus. In this paper, we present a case of successful surgical treatment of spontaneous rupture of the esophagus that was diagnosed 2 days after onset. The patient was a 42-year-old man admitted to internal medicine with a diagnosis of pleuritis and complaining of chest and back pain. The next day, computed tomography revealed left-sided pleural effusion and mediastinal emphysema. An esophagogram revealed extravasation of the contrast medium from the lower left esophagus to the mediastinal cavity. These results confirmed a rupture of the esophagus, and an emergency left thoracotomy was performed. The perforation was repaired with a single-layered closure and was covered with elevated great omentum obtained by laparotomy. The patient was discharged 23 days after the first surgery. In conclusion, primary repair surgery must be selected as the best treatment beyond 24 h if the patient’s general state was stable and there was no evidence of clinical sepsis.

Mass Screening of Lung Cancer by Computed Tomography in a Local Hospital.

【目的】肺癌検診におけるCTの有用性の検討【対象・方法】最近4年間に当院に人間ドック目的で入院した男性1335人, 女性19人の合計1354人. 年齢は22歳から66歳で平均48.3歳である. 検査項目は問診, 喀痰細胞診, 直接胸部単純写真 (以下胸単), 胸部X線CT (以下CT) である. CT導入前の胸単のみの検診1281人と比較する.【結果】 CTを用いた検診では1354人中5人 (0.37%) の肺癌が発見された (10万人対369). 内訳は高分化型腺癌3例, 低分化型腺癌1例, AAH 1例であった. 低分化型腺癌の1例はMissed caseである. いずれも胸単では指摘できなかった. 一方, CT導入前の胸単のみの検診では肺癌は発見できなかった.【考察】胸部CT検診の早期肺癌発見における有用性の報告は多くの施設によりなされている. 今回我々の検討では, 対象は比較的若年層であり, 通年検診症例である. CT導入前の肺癌発見が1281例中0例に対し, 導入後は1354例中5例であり1例を除き早期肺癌であった. 費用効果などあらゆる側面からCTの有用性を検討すべきであり, また対象とする集団の年齢構成や職種などにより適切な検診方法を検討すべきである.