The Hippo Signaling Pathway Components Lats and Yap Pattern Tead4 Activity to Distinguish Mouse Trophectoderm from Inner Cell Mass

Outside cells of the preimplantation mouse embryo form the trophectoderm (TE), a process requiring the transcription factor Tead4. Here, we show that transcriptionally active Tead4 can induce Cdx2 and other trophoblast genes in parallel in embryonic stem cells. In embryos, the Tead4 coactivator protein Yap localizes to nuclei of outside cells, and modulation of Tead4 or Yap activity leads to changes in Cdx2 expression. In inside cells, Yap is phosphorylated and cytoplasmic, and this involves the Hippo signaling pathway component Lats. We propose that active Tead4 promotes TE development in outside cells, whereas Tead4 activity is suppressed in inside cells by cell contact- and Lats-mediated inhibition of nuclear Yap localization. Thus, differential signaling between inside and outside cell populations leads to changes in cell fate specification during TE formation

Laparoscopy-Assisted Pancreaticoduodenectomy for Pancreatic Head Tumor at a Japanese Cancer Institute

Laparoscopic surgery is a less invasive treatment option for tumors in the intraabdominal organs; however, the safety and indication of laparoscopic or laparoscopy assisted pancreaticoduodenectomy (LPD) is still controversial. We attempted LPD in four cases for intraductal papillary mucinous neoplasm (IPMN) located in the pancreatic head and we report the surgical records and short-term outcome. LPD was carried out in four patients including three patients with the combined type IPMN and one with the branch type, based on the International Consensus Guidelines. None of the patients had invasive carcinoma based on preoperative imaging diagnosis. Laparoscopic procedures were performed until isolation of the pancreas head and duodenum, and final resection of PD and intestinal reconstruction were performed using small incision laparotomy (7-8cm). The mean total operating time was 882 minutes (820-932 minutes), mean blood loss was 925ml (610-1550ml) and red cell transfusion was not required in any patients. One patient underwent reoperation for bleeding at the pancreaticojejunostomy site at day 1. Mean duration until patients were able to walk was 3.5 days (2-6 days) and duration of use of analgesia was limited to within 7 days. Grade B pancreatic fistula was observed in one patient and jejunal ileus was observed in one patient. There were no deaths. LPD was safely performed and blood loss was limited, although the operating time was long. Postoperative recovery in patients without complications might be better than the conventional PD under laparotomy. Future study is necessary

A Predictive Factor of the Quality of Microarray Comparative Genomic Hybridization Analysis for Formalin-fixed Paraffin-embedded Archival Tissue

Utilizing formalin-fixed paraffin-embedded (FFPE) archival tissue, the most common form of tissue preservation in routine practice, for cytogenetic analysis using microarray comparative genomic hybridization (aCGH) remains challenging. We searched for a predictive factor of the performance of FFPE DNA in aCGH analysis. DNA was extracted from 63 FFPE archival tissue samples of various tissue types (31 breast cancers, 24 lung cancers, and 8 thyroid tumors), followed by aCGH analysis using high-density oligonucleotide microarrays. Tumor DNA from matched frozen samples and from FFPE samples after whole-genome amplification were also analyzed in 2 and 4 case, respectively. The derivative log ratio spread (DLRSpread) was used to assess the overall quality of each aCGH result. The DLRSpread correlated significantly with the double-stranded DNA ratio of tumor DNA, storage time, and the degree of labeling with Cy5 (P<0.0001; correlation coefficients=-0.796, 0.551, -0.481, respectively). Stepwise multiple linear regression analysis revealed that the double-stranded DNA ratio of tumor DNA is the most significant predictive factor of DLRSpread (regression coefficient=-0.4798; P=<0.0001). The cytogenetic profiles of FFPE and matched frozen samples showed good concordance. Although the double-stranded DNA ratios were increased after whole-genome amplification, the DLRSpread was not improved. The double-stranded DNA ratio can be used to predict the performance of aCGH analysis for DNA from FFPE samples. Using this quality metric, valuable FFPE archival tissue samples can be utilized for aCGH analysis

Predictive Parameters of Intraoperative Blood Loss in Patients who Underwent Pancreatectomy

Background/Aims: Despite recent advances in surgical techniques, blood loss is an important factor associated with postoperative outcomes in pancreatectomy. It is useful to identify risk factors of increased blood loss. Methodology: The clinical records of 161 patients who underwent an elective pancreatectomy for peripancreatic diseases between 1994 and March 2011 were retrospectively examined. Univariate and multivariate analysis of clinicopathological and surgical parameters influencing intraoperative blood loss were performed. We determined the cut-off value of the amount of blood loss based on the analyzed results. Results: The mean and median blood loss was 1346±901 and 1070 mL, respectively. Red cell blood transfusion was performed in 72 patients (45%). Based on ROC analysis, the predictive value of blood loss in patients who received red cell blood transfusion was 880 mL (p < 0.001); however, blood loss was not significantly associated with postoperative complications (p = 0.40). The cut-off level of estimated amount of blood loss in the present study was set at 880 mL. Male patients, fatty pancreas, higher serum alkaline phosphatase level, longer operating time, performance of pancreaticoduodenectomy (PD) and combined resections of adjacent major vessels were associated with significantly more increased blood loss (p < 0.05). Based on multivariate analysis, longer operation time over 480 minutes and performance of PD were significantly associated with increased blood loss (p < 0.05). Conclusions: Attempting to reduce operating time in cases of PD is necessary to reduce intraoperative blood loss

閉塞型睡眠時無呼吸症候群に合併する高血圧に対する経鼻持続陽圧呼吸療法の効果と問題点

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