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Conventional open distal pancreatectomy with en bloc celiac axis resection (DP-CAR) using the ventral approach is technically challenging, highly invasive, and not easy to ensure ample dorsal surgical margins. Hence, we describe a novel minimally invasive strategy for DP-CAR using the retroperitoneal-first laparoscopic approach (Retlap), i.e., Retlap DP-CAR, for locally advanced pancreatic body cancer (LAPC), and assess its utility.Retlap DP-CAR was performed in 10 patients with LAPC that was categorized as either unresectable (UR-LA, n = 4) or borderline (BR-A, n = 6). Neoadjuvant chemotherapy was applied on 8 patients and upfront surgery on 2. Retlap was used to create a working space in the retroperitoneal cavity between the pancreatic body and the left kidney and confirm technical resectability, such as securing the celiac axis and preserving the superior mesenteric artery in an early operative stage. Retlap DP-CAR was laparoscopic in 8 patients and robotic in 2. Surgical procedures are directly manipulated from the dorsal side of the pancreas and tumor, facilitating confirmation of technical resectability and obtaining ample dorsal margins in a no-touch isolation approach. Once technical resectability was confirmed, the procedure was converted to the ventral approach for completing DP-CAR.Median operating time and blood loss during Retlap were 271 min and 10 mL, respectively, while median resection time and intraoperative blood loss were 582 min and 412 mL, respectively. Tumor-free resection margins were obtained in all cases. The major morbidity rate (C-D IIIa) was 10%. No mortality was recorded within 90 days. Median overall survival was 53.8 months [95% confidence interval 32.7-75.0].Retlap DP-CAR is a novel minimally invasive procedure for resecting LAPC located close to the celiac axis. It is both safe and feasible, enables determination of technical resectability, achieves dorsal surgical margins, and can improve outcomes and QOL in patients with LAPC.

Background Distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) for borderline resectable pancreatic body cancer is increasingly being performed [ 1 , 2 ]. For survival benefits, obtaining margin-free resection (R0 resection) is crucial [ 3 ]. However, in patients with cancer abutting the root of the celiac axis and/or SMA, accurate resectability using preoperative imaging is difficult to judge [ 4 ]. Recently, we developed a novel strategy named “Retlap: Ret roperitoneal-first lap aroscopic ap proach” to achieve accurate evaluation of resectability and minimal invasiveness for difficult hepatopancreatobiliary malignancies and retroperitoneal tumors. Retlap enables direct evaluation of invasion of the roots of the celiac axis and SMA through the retroperitoneal approach. Methods This video demonstrates the case of a 50-year-old man with a 47 × 36-mm pancreatic body tumor after chemoradiotherapy. Preoperative computed tomography revealed tumor abutting on the roots of the celiac axis and SMA. Changes in the surrounding tissues due to chemoradiotherapy prevented accurate determination of the tumor invasion extent via preoperative imaging; thus, Retlap was applied. Retlap enabled us to identify and secure the roots of the celiac axis and SMA easily despite the advanced tumor. After confirming resectability, DP-CAR was performed. Results The operative time and estimated blood loss were 841 min and 572 mL. A negative surgical margin using Retlap was confirmed in frozen sections and R0 resection was achieved with uneventful postoperative course. Conclusion Retlap was technically feasible and useful for achieving accurate evaluation of resectability and minimal invasiveness for DP-CAR. Retlap can help provide optimal outcomes in locally advanced pancreatic cancer cases.

Tropomyosin-related kinase B (TrkB) plays an important role in tumor progression in various kinds of cancers; however, little is known about biological significance of TrkB in human lung cancer, especially large cell neuroendocrine carcinoma (LCNEC). We hereby investigated the expressions of TrkB and its ligand brain-derived neurotrophic factor (BDNF) in clinical specimens and their influences on phenotypes of invasiveness and tumorigenicity for LCNEC. The expressions of TrkB and BDNF analyzed by immunohistochemistry for patients samples with lung cancer (n=104) were significantly higher in neuroendocrine tumor (NET) compared with non-NET. In particular, LCNEC, a subtype of NET, exhibited significantly higher TrkB and BDNF expressions than another NET type: small cell lung cancer (SCLC), and a significant correlation between TrkB and BDNF expressions was noted in LCNEC but not in SCLC. In vitro assay, exogenous BDNF addition enhanced the invasion into matrigels of LCNEC cells, whereas inhibition of TrkB or BDNF suppressed matrix metalloproteinase-2 and -9 activities and the invasiveness. Exogenous BDNF also increased anchor-independent colony formation on soft agar gels for LCNEC, while inhibition of TrkB or BDNF suppressed the anchorage-independency. In vivo experiments, implanted LCNEC cells pretreated with TrkB-siRNA developed no subcutaneous tumor in all six nude mice, although those with control-siRNA formed tumors in four of six nude mice. In conclusion, BDNF/TrkB signal is involved in malignant progression of invasiveness and tumorigenicity for LCNEC, and may be a potential target for LCNEC without standard therapy.

Volatile organic compounds (VOCs) present at ppm levels were decomposed over the catalyst CuO–Co 3 O 4 –CeO 2 (Cu:Co:Ce = 10:45:45 in mol) in an attempt to scale up for industrial odor control. In addition to enhancing the catalytic activity, CuO–Co 3 O 4 and CeO 2 helped, respectively, to maintain the strength of the pelleted catalysts and inhibit their sintering. Using toluene as a VOC model compound, kinetic analysis of the total oxidation to carbon dioxide was conducted. The odor emitted from paint-drying processes could be eliminated effectively using CuO–Co 3 O 4 –CeO 2 (Cu:Co:Ce = 10:45:45) pelleted catalysts (188 ml) in a large-scale system.

Ubiquitin-dependent proteolysis is an important mechanism that suppresses the beta-catenin transcription factor in cells without Wnt stimulation. A critical step in this regulatory pathway is to create a SCF(beta-TrCP) E3 ubiquitin ligase binding site for beta-catenin. Here we show that the SCF(beta-TrCP) binding site created by phosphorylation of beta-catenin is highly vulnerable to protein phosphatase 2A (PP2A) and must be protected by the adenomatous polyposis coli (APC) tumor suppressor protein. Specifically, phosphorylated beta-catenin associated with the wild-type APC protein is recruited to the SCF(beta-TrCP) complex, ubiquitin conjugated, and degraded. A mutation in APC that deprives this protective function exposes the N-terminal phosphorylated serine/threonine residues of beta-catenin to PP2A. Dephosphorylation at these residues by PP2A eliminates the SCF(beta-TrCP) recognition site and blocks beta-catenin ubiquitin conjugation. Thus, by acting to protect the E3 ligase binding site, APC ensures the ubiquitin conjugation of phosphorylated beta-catenin.

The reliability of Cu interconnects was successfully improved by applying a CuAl alloy seed. However, the effect of additive Al on the reliability is not fully understood. In order to reveal the reliability improvement mechanism, Cu films using CuAl alloy seed were investigated in detail. As stress induced voiding (SIV) as well as electromigration is caused by migration of vacancies and/or Cu atoms, the measured activation energy value of electromigration using CuAl indicates that the fast diffusion paths are Cu grain boundaries. The analysis using high lateral resolution scanning type secondary ion mass spectrometry (nano-SIMS) clarifies that additive Al in ECP-Cu film is mainly localized at grain boundaries. Furthermore, positron annihilation was used to probe vacancy-type defects in Cu films. The CuAl films before recrystallization contain larger and higher density vacancy-type defects. Whereas, the recrystallized CuAl films after annealing above 250^oC contain smaller and lower density defects. Furthermore, CuAl films with annealing above 350^oC contain less Al inside the grains. These results represent that Al atoms in Cu films with annealing above 350^oC are exhausted from inside grains to the grain boundaries, and the spewed Al atoms existing at Cu grain boundary effectively prevents the diffusion of Cu and/or vacancies.

Interleukin (IL)-2 and IL-4 play a critical role in the regulation of the immune response. Yet both of the receptors for these cytokines have been found on nonhematopoietic cells, including human gastric carcinoma cell lines and tissue specimens. IL-4 causes G1 phase cell cycle arrest of gastric carcinoma; the effect directly correlates with the expression of IL-4 receptor (IL-4R) and is seen within 48 hours after treatment. Cells lacking IL-4R are unaffected by IL-4. We examined signal transduction pathways employed by IL-4 that may account for cell cycle arrest of an established human gastric carcinoma cell line, CRL 1739. Western blot analysis was performed on CRL 1739 cultured in the presence of IL-4 (500 U/ml). Cells were lysed, protein extracted, and electroblotted; blots were then probed with murine monoclonal antibodies to specific intracellular proteins. Western blotting of CRL 1739 with antiphosphotyrosine antibody (4G10) demonstrated multiple (140 kDa and 65 kDa) phosphoproteins seen only in IL-4—treated CRL 1739. Immunoprecipitation and blotting of CRL 1739 with specific secondary antibodies demonstrated that the 140 kDa phosphoprotein was IL-4Rα, the 65kDa phosphoprotein was IL-2Rγc, the 130 kDa phosphoprotein was Janus kinase (JAK1), and the 116 kDa phosphoprotein was JAK3. Reverse transcription—polymerase chain reaction with specific primers demonstrated that multiple human gastric tumor specimens expressed IL-4Rα and IL-2Rγc but did not express the leukocyte marker CD45. These results suggest that human gastric carcinomas may express functional cytokine receptors, including the IL-2Rγc commonly found in association with the lymphocyte IL-2R. These receptors may represent novel targets for directing cytokine-based therapy.

Aims Although axillary lymph nodes status, tumour size, hormonal-receptor status and histological grade at diagnosis are frequently used to orient the treatment of breast cancer patients, some tumours recur in patients with early stage disease. Pre-operative assessment of individual tumour characteristics, based on oncogenes and growth factors related to tumour growth, invasion or metastasis, may guide the treatment for patients with breast carcinomas. Methods We examine here the prognostic significance of cyclin D1, urokinase type plasminogen activator, vascular endothelial growth factor (VEGF), platelet-derived growth factor, and c-erbB2 expression in pre-operatively obtained fine-needle aspirates from breast carcinomas less than or equal to 3cm in size. Correlation between mRNA expression of these factors and clinicopathological characteristics was analysed. Results The level of c-erbB2 mRNA expression was significantly higher in tumours with lymph node metastases than in those without lymph node metastases. VEGF mRNA expression positively correlated with the degree of angiogenesis as quantitated by immunohistological staining with a CD31 monoclonal antibody. Conclusions Analysis of c-erbB2 and VEGF mRNA expression in fine-needle aspirates may be useful in assessing the malignant potential of individual breast carcinomas, leading to a pre-operative discrimination of a high-risk group.