In this study, we report for the first time reduced expression of the let-7 microRNA in human lung cancers. Interestingly, 143 lung cancer cases that had undergone potentially curative resection could be classified into two major groups according to let-7 expression in unsupervised hierarchical analysis, showing significantly shorter survival after potentially curative resection in cases with reduced let-7 expression (P ‫؍‬ 0.0003). Multivariate COX regression analysis showed this prognostic impact to be independent of disease stage (hazard ratio ‫؍‬ 2.17; P ‫؍‬ 0.009). In addition, overexpression of let-7 in A549 lung adenocarcinoma cell line inhibited lung cancer cell growth in vitro. This study represents the first report of reduced expression of let-7 and the potential clinical and biological effects of such a microRNA alteration.

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Background:A British randomised study of gemcitabine plus cisplatin (GC) combination showed promising results in biliary tract cancer (BTC) patients. In our study, we evaluated the efficacy and safety of this combination compared with gemcitabine alone (G) in Japanese BTC patients.Methods:Overall, 84 advanced BTC patients were randomised to either cisplatin 25 mg m−2 plus gemcitabine 1000 mg m−2 on days 1, 8 of a 21-day cycle (GC-arm), or single-agent gemcitabine 1000 mg m−2 on days 1, 8 and 15 of a 28-day cycle (G-arm). Treatments were repeated for at least 12 weeks until disease progression or unacceptable toxicity occurred, up to a maximum of 48 weeks.Results:A total of 83 patients were included in the analysis. For the GC and G-arms, respectively, the 1-year survival rate was 39.0 vs 31.0%, median survival time 11.2 vs 7.7 months, median progression-free survival time 5.8 vs 3.7 months and overall response rate 19.5 vs 11.9%. The most common grade 3 or 4 toxicities (GC-arm/G-arm) were neutropenia (56.1%/38.1%), thrombocytopenia (39.0%/7.1%), leukopenia (29.3%/19.0%), haemoglobin decrease (36.6%/16.7%) and γ-GTP increase (29.3%/35.7%).Conclusions:Gemcitabine plus cisplatin combination therapy was found to be effective and well tolerated, suggesting that it could also be a standard regimen for Japanese patients.

The p53 tumor suppressor gene, which is induced by DNA damage and/or stress stimuli, causes cells to undergo G1-arrest or apoptotic death; thus it plays an essential role in human carcinogenesis. We have searched for p53-related genes by using degenerate PCR, and have identified two cDNA fragments similar to but distinct from p53: one previously reported, p73, and the other new. We cloned two major splicing variants of the latter gene and named these p51A and p51B (a human homologue of rat Ket). The p51A gene encodes a 448-amino-acid protein with a molecular weight of 50.9 kDa; and p51B, a 641-amino-acid protein with a molecular weight of 71.9 kDa. In contrast with the ubiquitous expression of p53, expression of p51 mRNA was found in a limited number of tissues, including skeletal muscle, placenta, mammary gland, prostate, trachea, thymus, salivary gland, uterus, heart and lung. In p53-deficient cells, p51A induced growth-suppression and apoptosis, and upregulated p21waf-1 through p53 regulatory elements. Mutations in p51 were found in some human epidermal tumors.

PVE has the potential benefit for patients with advanced biliary cancer who are to undergo extended, complex hepatectomy. Along with the use of PVE, further improvements in surgical techniques and refinements in perioperative management are necessary to make difficult hepatobiliary resections safer.

Microscopic invasion of the portal vein may be misdiagnosed clinically in patients with hilar cholangiocarcinoma. However, the distance between tumor and adventitia is so narrow that curative resection without portal vein resection is unlikely to be possible. Gross portal vein invasion has a negative impact on survival, and hepatectomy with portal vein resection can offer long-term survival in some patients with advanced hilar cholangiocarcinoma.

From 1979 through 1989, surgical resection was performed in 55 of 66 patients with carcinoma of the hepatic hilus after improving jaundice by percutaneous transhepatic biliary drainage (PTBD). Selective cholangiography through PTBD was done to define precisely the anatomical location--extent of the obstructing lesion in each segmental hepatic duct. Percutaneous transhepatic cholangioscopy was performed through the sinus tract of PTBD after replacing the drainage catheter with a 15 French catheter for superselective cholangiography and biopsy to make the definitive diagnosis of the histological extent of the tumor and any variation of each segmental hepatic duct that joins the hepatic hilus. In 46 (69.7%) of 66 patients, curative resection was possible. Forty-five of these underwent various types of hepatic segmentectomy with caudate lobectomy for a morbidity rate of 41.3% and an operative mortality rate of 6.4%. Fourteen (31.1%) advanced cases underwent combined resection of the portal vein together with hepatectomy. Microscopic tumor involvement in the caudate branches was confirmed in 44 of 45 patients who underwent caudate lobe resection. The 3-year survival rate for all 43 patients surviving the curative excision was 55.1% and the 5-year survival rate was 40.5%. All 11 patients who had an unresectable advanced tumor died within 9 months. Curative resection should be designed according to the preoperative findings of the extent of cancer in each segmental duct, and caudate lobe resection should be performed together with the smallest necessary hepatic segmentectomy possible.