Yoshitoshi Sato

Clinicopathological significance of Ki-ras point mutation and p21 expression in benign and malignant exocrine tumors of the human pancreas

SummaryConclusionThe present study suggests that Ki-raspoint mutations may play an important role in the early stages of tumorigenesis and that a double mutation has a stronger detrimental effect than a single mutation on the survival after pancreatectomy.BackgroundPrevious studies have suggested the important role of Ki-ras point mutations inras gene codon 12 in the tumorigenesis of pancreatic cancer, but their clinicopathological significance is still unclear. The present study was designed to assess the clinicopathological significance of Ki-ras point mutations, and p21 expression in malignant and benign diseases of the pancreas.MethodsOligonucleotide dot-blot hybridization for Ki-ras point mutations in codon 12 and immunohistochemical staining for p21 expression were applied. Cases included 44 primary and 15 metastatic lesions of pancreatic cancer, and 17 benign pancreatic diseases.ResultsKi-ras point mutations and p21 expression were detected in 43 and 19 primary lesions, 9 and 6 metastatic lesions, and four and five benign diseases, respectively. The patients with a single mutation had a better survival after pancreatectomy than those with a double mutation. The patients with a p21(+) GAT mutation showed the worst survival after pancreatectomy compared with other categories of patients.

Comparative Study of p53 Expression in Primary Invasive Ductal Carcinoma of the Pancreas Between Chinese and Japanese

Previous studies reported different frequencies of p53 expression between Japanese and Americans or Europeans. The present study was designed to clarify whether there is a significant difference in p53 expression and its clinical implications between Chinese and Japanese patients with primary invasive ductal carcinoma (IDC) of the pancreas. p53 expression was studied in 39 Chinese and 47 Japanese patients, and immunostaining with the SAB method was performed using anti-p53 monoclonal antibody (DO-1) in formalin-fixed and paraffin-embedded specimens. Clinical data were analyzed according to the International Union Against Cancer classification. p53 expression was seen in 71.8% of Chinese and in 48.9% of Japanese patients with IDCs of the pancreas (p <0.05). The Chinese patients were significantly younger than the Japanese ones (p <0.05), but there were no significant corre lations between p53 immunoreactivity and age, gender, stage, and histopathological grade in separate analyses of the Chinese and Japanese patients. A comparison between them showed that in patients younger than 55 and 65 years old, the incidence of p53 expression was markedly lower in Japanese than in Chinese (p <0.05). In Japanese patients, those with a p53-positive pancreatic cancer had a significantly lower survival rate than those with a p53-negative tumor, but there was no correlation between p53 expression and the prognosis of Chinese patients. The frequency of p53 expression in IDC of the pancreas is higher in Chinese than in Japanese patients, and the effect of p53 expression on prognosis is different between Chinese and Japanese patients.

Ki-ras point mutation in codon 12 and expression of p53 in mucin-producing tumor of the pancreas

Mucin-producing tumors (MPTs) of the pancreas show a variety of clinical characteristics, including massive production of mucin in the pancreatic duct, dilatation of the main pancreatic duct, and a better prognosis than common invasive ductal carcinoma (IDC). These characteristics suggest that MPTs and IDCs have different cytomolecular backgrounds. The present study was designed to assess the differences in cytomolecular background between MPTs and IDCs, especially the differences in Ki-ras point mutation (PM) and wild and mutant typep53 expression. Cytomolecular backgrounds were compared in a 13 MPTs [8 carcinomas (MPCas) and 5 benign tumors (MPBTs)] and 36 IDCs. Cytomolecular studies included the evaluation of Ki-ras PM and the expression of Ki-ras p21, wild-typep53 (w-p53), and mutant-typep53 (m-p53). Ki-ras PM was assessed by the allele-specific oligonucleotide dot blot hybridization method, and the expression of p21 andp53 was assessed by an immunohistochemical staining method with monoclonal antibodies. Ki-ras PM was seen in 97% of IDCs and in 77% of MPTs (100% of MPCas and 40% of MPBTs), and MPBTs showed a significantly lower incidence of Ki-ras PM (versus IDC,P < 0.01). Guanine-Guanine-Thymine (GGT) to Guanine-Adenine-Thymine (GAT) mutation was seen in 55% of IDCs and 62% MPTs (87% of MPCas and 20% of MPBTs), and MPCas showed a significantly higher incidence of percent GAT mutation (versus IDC,P < 0.05). Ki-ras p21 was expressed in 43% of IDCs and in 31 % of MPTs (50% of MPCas and 20% of MPBTs). w-p53 and m-p53 were expressed in 51 % and 78% of IDCs and in 54% and 62% of MPTs (38% and 63% of MPCas and 20% and 60% of MPBTs), respectively. In MPBTs, hyperplasias showed higher rates of p21, w-p53, and m-p53 expression than cystadenomas. The study suggested that GAT mutation may be involved in the tumorigenesis of MPTs. It is suggested that MPBTs, especially hyperplasias, may be classified as low-grade malignancies like MPCas.

Treatment of Choledocholithiasis Using Balloon Dilatation of the Papilla Via the Common Bile Duct.

総胆管結石症10例に対して経胆管的にバルーンカテーテルを十二指腸乳頭部まで誘導し, 乳頭を拡張することによって治療を行った. カテーテルの挿入ルートは, 経皮経肝胆道ドレナージの瘻孔経由4例, 腹腔鏡下胆嚢摘出術術中胆嚢管経由5例, 腹腔鏡下胆嚢摘出術後経胆嚢管的ドレナージチューブの瘻孔経由が1例であった. 結石径が10mm以上の4例に対してダイ・レーザーによる胆道鏡下砕石術を併用した.10例中9例で1回ないし2回の乳頭拡張によって除石に成功したが, 1例でESTの併用が必要であった. 一過性の高アミラーゼ血症を2例, 胆管炎を1例認めたが, 重篤な合併症は経験しなかった. 術後1年6か月の1症例で結石の再発を認めた. 経胆管的十二指腸乳頭拡張術は, 手技的に容易であり, 合併症も少なく総胆管結石治療の1つの選択肢として有用であると思われた.