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Pulmonary neuroendocrine (NE) cells are rare airway epithelial cells. The balance between Achaete‐scute complex homolog 1 (ASCL1) and hairy and enhancer of split 1, one of the target molecules of the Notch signaling pathway, is crucial for NE differentiation. Small cell lung cancer (SCLC) is a highly aggressive lung tumor, characterized by rapid cell proliferation, a high metastatic potential, and the acquisition of resistance to treatment. The subtypes of SCLC are defined by the expression status of NE cell‐lineage transcription factors, such as ASCL1, which roles are supported by SRY‐box 2, insulinoma‐associated protein 1, NK2 homeobox 1, and wingless‐related integration site signaling. This network reinforces NE differentiation and may induce the characteristic morphology and chemosensitivity of SCLC. Notch signaling mediates cell‐fate decisions, resulting in an NE to non‐NE fate switch. The suppression of NE differentiation may change the histological type of SCLC to a non‐SCLC morphology. In SCLC with NE differentiation, Notch signaling is typically inactive and genetically or epigenetically regulated. However, Notch signaling may be activated after chemotherapy, and, in concert with Yes‐associated protein signaling and RE1‐silencing transcription factor, suppresses NE differentiation, producing intratumor heterogeneity and chemoresistance. Accumulated information on the molecular mechanisms of SCLC will contribute to further advances in the control of this recalcitrant cancer. [ABSTRACT FROM AUTHOR]

To enable the efficient delivery of drugs to the lungs, the drug particle design for most dry powder inhalers (DPIs) involves reducing the aerodynamic particle size to a few microns using methods such as spray-drying or jet-milling. Stresses, including heat and the shear forces generated by the preparation processes, may result in the degradation and denaturation of drugs such as those based on peptides and proteins. Here, we showed that cryo-milled polyvinyl alcohol nanofiber mats loaded with α-chymotrypsin by electrospinning exhibited suitable inhalation properties for use in DPIs, while maintaining enzymatic activity. The cryo-milled nanofiber mats were porous to fine particles, and the particle size and drug stability depended on the freezing and milling times. The median diameter of the milled fiber mats was 12.6 μm, whereas the mass median aerodynamic diameter was 5.9 μm. The milled nanofiber mats were successfully prepared, while retaining the enzymatic activity of α-chymotrypsin; furthermore, the activity of milled fiber mats that had been stored for 6 months was comparable to the activity of those that were freshly prepared. This novel method may be suitable for the DPI preparation of various drugs because it avoids the heating step during the DPI preparation process. [ABSTRACT FROM AUTHOR]

Slightly acidic electrolyzed water (SAEW) was developed by Japanese companies over 20 years ago. SAEW has the advantage of potent sterilizing action while being relatively safe. This study evaluated the potential application of SAEW in spatial disinfection. Prior to experiments involving spatial spraying, the ability of SAEW to remove seven type of microorganisms that cause food poisoning was studied in vitro. Results indicated that free chlorine in SAEW, even at a low concentration (30 mg/L), was able to remove Cladosporium cladosporioides, a typical airborne fungus that degrades food, and spores such as Bacillus subtilis, a hardy bacterium. In an experiment involving spatial spraying, 3.43 log10 CFU/100 L of Staphylococcus epidermidis was sprayed in a room-sized space; the same space was then sprayed with SAEW. The number of settling microbes was measured and the sterilizing ability of SAEW was assessed. Results indicated that the concentration of S. epidermidis in the space was completely removed after 20 minutes of SAEW spraying. The above findings indicate that SAEW may be used to remove airborne microorganisms via spatial spraying. [ABSTRACT FROM AUTHOR]

Background: Biliary confluence is sometimes involved in colorectal liver metastasis (CRLM), and therefore bile duct resection (BDR) is occasionally necessary for complete resection. However, the utility of hepatectomy with combined BDR is unclear. The safety and survival outcome of hepatectomy with combined BDR for CRLM was assessed. Methods: Patients who underwent hepatectomy for CRLM between 2002 and 2017 were identified from a prospectively compiled database. Postoperative outcomes were compared between patients undergoing hepatectomy alone and with combined BDR for CRLM. Results: A total of 734 patients who underwent hepatectomy for CRLM were included. Hepatectomy with combined BDR was performed in 16 (2.1%) patients. The postoperative complications rate (Clavien–Dindo ≥ 3) of patients undergoing hepatectomy with BDR was 31.2%, which was higher than that without BDR (P = 0.001) for CRLM. The mortality rate of surgery for CRLM was 0%. The 5- and 10-year relapse-free survival (RFS) rates for hepatectomy with BDR were 45.0% and 30.0%, respectively. Patients undergoing hepatectomy with BDR had a similar RFS to those without BDR for CRLM (P = 0.351). The 5- and 10-year overall survival (OS) rates for hepatectomy with BDR were 62.6% and 62.6%, respectively. Patients undergoing hepatectomy with BDR had a similar OS to those without BDR for CRLM (P = 0.738). Conclusions: In conclusion, hepatectomy with combined BDR was a potentially feasible treatment option that obtained favorable survival outcomes in patients with invasion of the biliary confluence by CRLM, although BDR with hepatectomy for CRLM was associated with a high rate of morbidity. [ABSTRACT FROM AUTHOR]

Purpose: Adenosquamous carcinoma (ASC) of the pancreas is a rare malignancy, associated with a poor prognosis after surgical resection, with reported median survival times (MSTs) ranging from 4.4 to 13.1 months. We conducted this study to investigate the long-term outcomes of patients after the resection for ASC. Methods: Between 2002 and 2016, a total of 456 patients underwent resection for ASC or adenocarcinoma (AC) of the pancreas. ASC was confirmed in 17 (3.7%) of these patients. We analyzed the clinicopathological characteristics and survival of these 17 patients in comparison with those of patients with AC of the pancreas. Results: The operative procedures performed were pancreaticoduodenectomy (n = 6) and distal pancreatectomy (n = 11). Seven (41.2%) of the 17 patients underwent combined organ resection. R0 resection was achieved in 16 (94.1%) patients. The 5-year overall survival (OS) rate and MST were 40.3% and 20.9 months, respectively. A squamous component of ≥ 60% (P = 0.001) and R1 resection (P < 0.001) were significantly associated with poor OS for patients with ASC Conclusion: This study revealed longer survival and a higher R0 resection rate after aggressive combined resection in our ASC patients than those in previous studies. Although this was only a small series, our findings suggest that local control with aggressive resection may be an effective treatment protocol for ASC patients. [ABSTRACT FROM AUTHOR]

Postoperative complications affect both the short-term and long-term outcomes. The aim of this study was to identify specific prognostic factors among complications after hepatectomy for colorectal liver metastasis (CRLM). Between 2002 and 2014, 427 patients underwent initial hepatectomy for CRLM. The clinicopathological parameters including postoperative complications were evaluated to identify the prognostic factors for the overall (OS) and relapse-free survival (RFS). One hundred and forty-nine patients (34%) developed postoperative complications, including surgical site infection (n = 49, 11.4%), bile leakage (n = 41, 9.6%), posthepatectomy liver failure (PHLF) (n = 26, 6.0%), and pulmonary complication (n = 20, 4.6%). The independent predictors of RFS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, bilateral CRLMs, ≥5 CRLMs, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year RFS rates in patients with and without PHLF were 8% and 32%, respectively (P < 0.001). The independent prognostic factors for OS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, positive surgical margins, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year OS rates in patients with and without PHLF were 31% and 63%, respectively (P = 0.004). Among the complications, only PHLF was associated with decreased long-term survival after hepatectomy for CRLM as well as tumor-specific prognostic factors. [ABSTRACT FROM AUTHOR]

In order to evaluate the in vivo effect of inhaled formulations, it is a gold standard to create a lung metastasis model by intravenously injecting cancer cells into an animal. Because the cancer grows from the blood vessel side, there is a possibility of underestimating the effect of an inhaled formulation administered to the lung epithelium side. In addition, the metastasis model has disadvantages in terms of preparation time and expense. The present study aimed to establish a new method to evaluate the effect of an inhaled small interfering RNA (siRNA) formulation that is more correct, more rapid, and less expensive. We investigated whether siRNA can suppress gene expression of plasmid DNA (pDNA) by serial pulmonary administration of siRNA and pDNA powders prepared by spray-freeze-drying. We revealed that formulations of dry siRNA powder significantly suppressed gene expression of pDNA powder compared with a control group with no siRNA. Naked siRNA inhalation powder with no vector showed the suppression of gene expression equivalent to that of an siRNA-polyethyleneimine complex without damaging tissues. These results show that the present method is suitable for evaluating the gene-silencing effect of inhaled siRNA powders. [ABSTRACT FROM AUTHOR]

[Display omitted] • We prepared ibuprofen-isonicotinamide co-crystal granules. • The granules were produced directly and continuously by a continuous-spray granulator. • The granulation conditions affected the particle size and the yield of the granules. • Compared to ibuprofen bulk, the granules improved the circularity and the flowability. • The co-crystallization did not change the solubility of ibuprofen. The importance of granulation is paramount for tablet manufacturing, and is based on the fact that granulated powders are characterized by improved flowability, compressibility, segregation, and dust reduction. The aim of this study was to prepare and characterize continuous granules of high drug content by using a continuous-spray granulator (CTS-SGR). Ibuprofen (IBU), a drug of low-flowability, was selected as the model drug. As IBU has a low melting point and cannot easily granulate on its own, we employed isonicotinamide (INA) as a coformer that would allow us to prepare co-crystal granules containing 60 % IBU. The results of the undertaken differential scanning calorimetry and powder X-ray diffraction revealed that the IBU and the INA in the granules formed co-crystals. The granulation conditions affected the particle size and the yield of the granules; in fact, a low air supply temperature, a low atomizing air rate, and a high solution flow rate ensured a high granulation efficiency. Moreover, continuous granulation increased the yields of the formulations compared to those obtained through a short-run granulation, and high yields were obtained after applying a low atomizing air rate. The circularity of the granules exceeded 90 %, and their flowability improved when compared to that of the IBU bulk. The undertaking of dissolution studies revealed no change in the elution amount of IBU as a result of the co-crystallization. Our study shows that it is possible to produce high-content IBU granules in a direct and continuous manner through the co-crystallization of IBU and the use of a CTS-SGR. [ABSTRACT FROM AUTHOR]

Purpose This work studies the detective quantum efficiency ( DQE) of a-Se-based solid state x-ray detectors for medical imaging applications using ARTEMIS, a Monte Carlo simulation tool for modeling x-ray photon, electron and charged carrier transport in semiconductors with the presence of applied electric field. Methods ARTEMIS is used to model the signal formation process in a-Se. The simulation model includes x-ray photon and high-energy electron interactions, and detailed electron-hole pair transport with applied detector bias taking into account drift, diffusion, Coulomb interactions, recombination and trapping. For experimental validation, the DQE performance of prototype a-Se detectors is measured following IEC Testing Standard 62220-1-3. Results Comparison of simulated and experimental DQE results show reasonable agreement for RQA beam qualities. Experimental validation demonstrated within 5% percentage difference between simulation and experimental DQE results for spatial frequency above 0.25 cycles/mm using uniform applied electric field for RQA beam qualities ( RQA5, RQA7 and RQA9). Results include two different prototype detectors with thicknesses of 240 μm and 1 mm. Conclusions ARTEMIS can be used to model the DQE of a-Se detectors as a function of x-ray energy, detector thickness, and spatial frequency. The ARTEMIS model can be used to improve understanding of the physics of x-ray interactions in a-Se and in optimization studies for the development of novel medical imaging applications. [ABSTRACT FROM AUTHOR]

Background: The American Joint Committee on Cancer (AJCC) has recommended that cancers with liver involvement be graded T2b and those with portal vein involvement be graded T3, although the value of staging as prognostic factors remains unclear. We evaluated the current definition of the T2/3 tumors for perihilar cholangiocarcinoma. Methods: A total of 202 patients with perihilar cholangiocarcinoma who underwent hepatectomy without vascular resection were enrolled. Clinicopathologic data about invasion of the liver and the unilateral portal vein were evaluated. Results: The liver and the unilateral portal vein were involved in 100 (49.5 %) and 38 (18.8 %) patients, respectively. The survival rates were not significantly different between patients with and without liver invasion (48.6 vs. 52.2 %, respectively, at 5 years, P = 0.157) and between patients with or without unilateral portal vein invasion (43.2 vs. 52.1 %, respectively, at 5 years, P = 0.363). The survival rate of patients with tumors staged pT2b was not significantly different from the rate of patients with pT2a (63.4 vs. 55.6 % at 5 years, P = 0.912), and the pT2b tumor patient survival rate was better than the rate of patients with pT3 (34.9 % at 5 years, P = 0.011). Using multivariate analysis, nodal metastasis ( P = 0.003), positive surgical margin ( P = 0.010), and Bismuth type IV tumor ( P = 0.039) were identified as independent prognostic factors. Conclusions: The liver and the unilateral portal vein are frequently involved in perihilar cholangiocarcinoma. The determinants of the current AJCC T2/3 tumor classifications are rational; however, subdivision of T2 tumors may be of less clinical value. [ABSTRACT FROM AUTHOR]

Background: It remains controversial whether anatomical resection (AR) improves the prognosis for hepatocellular carcinoma (HCC) or not. To our knowledge, there have been a few well-matched studies about this issue. The aim of the present study was to compare the recurrence-free survival of AR versus nonanatomical resection (NAR) for a solitary HCC using propensity score matching.Methods: The present study included 236 patients who had a solitary HCC without macroscopic vessel thrombosis. Those patients were divided into AR (n = 139) and NAR (n = 97) groups. A propensity score matching was performed to minimize the effect of potential confounders.Results: Sixty-four patients from each group were matched. Preoperative confounding factors were balanced between the two groups. The median recurrence-free survival times in the AR and NAR groups were 33.8 and 30.8 months, respectively (P = 0.520). There were no significant differences in the intrahepatic recurrence pattern (P = 0.097). Operative procedure was not a significant risk factor for recurrence in both uni- and multivariate analyses.Conclusions: This case-matching study using a propensity score shows that there is no superiority of AR to NAR relevant to the recurrence-free survival in patients with a single HCC. [ABSTRACT FROM AUTHOR]

Background: It remains controversial whether anatomical resection (AR) improves the prognosis for hepatocellular carcinoma (HCC) or not. To our knowledge, there have been a few well-matched studies about this issue. The aim of the present study was to compare the recurrence-free survival of AR versus nonanatomical resection (NAR) for a solitary HCC using propensity score matching. Methods: The present study included 236 patients who had a solitary HCC without macroscopic vessel thrombosis. Those patients were divided into AR ( n = 139) and NAR ( n = 97) groups. A propensity score matching was performed to minimize the effect of potential confounders. Results: Sixty-four patients from each group were matched. Preoperative confounding factors were balanced between the two groups. The median recurrence-free survival times in the AR and NAR groups were 33.8 and 30.8 months, respectively ( P = 0.520). There were no significant differences in the intrahepatic recurrence pattern ( P = 0.097). Operative procedure was not a significant risk factor for recurrence in both uni- and multivariate analyses. Conclusions: This case-matching study using a propensity score shows that there is no superiority of AR to NAR relevant to the recurrence-free survival in patients with a single HCC. [ABSTRACT FROM AUTHOR]

Abstract: Background: Exposure of skin to long-wave UV radiation (UVA) increases the cellular levels of reactive oxygen species (ROS), which have been linked to apoptosis induction through the damage of lipids, proteins, and nucleic acids. Peroxiredoxin I (Prx I) is one of a family of antioxidant proteins that plays a protective role against oxidative damage; however the role of Prx I in UVA-induced damage remains to be clarified. Objective: Here we investigated the protective role of Prx I against UVA-induced changes using mouse embryonic fibroblasts (MEFs) derived from Prx I homozygous knockout (Prx I (−/−)) mice. Methods: Prx I (−/−) and wild-type (Prx I (+/+)) MEFs were subjected to UVA irradiation, and the resulting apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blotting. Results: Prx I (−/−) MEFs showed enhanced sensitivity to UVA treatment, exhibiting increased apoptosis and ROS production compared to Prx I (+/+) MEFs. Consistent with the increase in apoptosis, p53 expression was significantly higher, while Bcl-2, Bcl-xL, and Nrf2 expressions were all lower in Prx I (−/−) versus (+/+) MEFs. The UVA-induced inflammatory response was upregulated in Prx I (−/−) MEFs, as indicated by increased expressions of IκB, TNFα, and IL-6. Evidence was presented indicating that Prx I impacts these pathways by modifying critical signaling intermediates including p53, IκB, and Nrf2. Conclusion: Our results indicate that Prx I plays a protective role against UVA-induced oxidative damage by controlling ROS accumulation. Both the UVA-induced apoptotic and inflammatory signals were found to be modulated by Prx I. [Copyright &y& Elsevier]

Abstract: The interleukin-6 (IL-6) family of cytokines is thought to be involved in the development and regeneration of peripheral nerves; however, their roles in myelination remain unclear. In this study, we examined the effects of IL-6 on the expression of genes for compact myelin proteins using Schwann cell cultures prepared by multiple explantation of adult rat sciatic nerves. In semi-quantitative reverse transcription-polymerase chain reaction analysis, stimulation of Schwann cells with IL-6 significantly increased the mRNA level of peripheral myelin protein 22 (PMP22), but not those of myelin protein zero and myelin basic protein. The increase in PMP22 mRNA was markedly suppressed by AG490, a Janus kinase 2 (JAK2) inhibitor, but not significantly by PD098059, a mitogen-activated protein kinase inhibitor. Immunocytochemical staining revealed that IL-6 enhanced immunoreactivities for the phosphorylated forms of both JAK2 and signal transducer and activator of transcription 3 (STAT3), as well as that for PMP22. These results indicate that IL-6 can enhance PMP22 production in Schwann cells via a JAK2-dependent pathway by probably activating STAT3 and thus may contribute to myelination. [Copyright &y& Elsevier]

To investigate the possibility of‘de novo’ prostate cancer by analyzing the relationship between high grade prostatic intraepithelial neoplasia (HGPIN) and latent prostate cancer.Latent prostate cancers found at autopsy were examined and 55 cancer foci with a poorly (Gleason grade 4 and 5) or moderately (Gleason grade 3) differentiated component were selected. The 55 foci were separated into two groups: (i) foci with either a poorly or moderately differentiated component only (single differentiation group, SDG); and (ii) mixed foci with two or more types of differentiation components (mixed differentiation group, MDG). High grade intraepithelial neoplasia was defined as positive if it was observed within 2 mm from the edge of the cancer focus and the relationship between HGPIN and the two groups was investigated.The MDG had 39 cancer foci (71.0%) and there were 16 in the SDG (29.0%). There were 31 foci that were small-volume cancers (<0.2 mL). In the MDG, 13 small-volume cancer foci were HGPIN positive, but in the SDG, none of the small-volume cancers were HGPIN positive.Small-volume cancer foci without HGPIN in the SDG may be candidates for de novo prostate cancers. [ABSTRACT FROM AUTHOR]

To investigate retrospectively whether the eight-core biopsy method improves the prostate cancer detection rate when compared with the standard sextant biopsy method in patients with prostate specific antigen (PSA) levels of 4.1–10 ng/mL. Of 437 patients whose PSA levels ranged from 4.1 to 10 ng/mL, 237 underwent a transrectal ultrasound guided sextant biopsy (sextant group), and 200 underwent an eight-core biopsy (eight-core group). Eight core samples were obtained from each of the far lateral regions in addition to the standard sextant biopsy cores. None of the patients had a previous history of prostate biopsy. Of the 237 patients in the sextant group, prostate cancer was detected in 47 patients (19.8%) and in 50 of the 200 patients in the eight- core group (25.0%). The rates of detection in the two methods were not statistically significant. However, in patients whose PSA density was less than 0.1 ng/mL per cc, the cancer detection rates in the sextant group and the eight-core group were 4.5% and 18.8%, respectively ( P = 0.046). The morbidity and complications of the eight-core biopsy method were not notable. Only in patients with PSA levels of 4.1–10 ng/mL and density of less than 0.1 ng/mL per cc was the eight-core biopsy method an improvement on the sextant biopsy method in terms of prostate cancer detection rate. Accordingly, a number of cores greater than eight will be required to improve the cancer detection rates in patients with PSA levels of 4.1–10 ng/mL and PSA densities of more than 0.1 ng/mL per cc. [ABSTRACT FROM AUTHOR]

Rcd1, initially identified as a factor essential for the commitment to nitrogen starvation-invoked differentiation in fission yeast, is one of the most conserved proteins found across eukaryotes, and its mammalian homolog is expressed in a variety of differentiating tissues. Here we show that mammalian Rcd1 is a novel transcriptional cofactor and is critically involved in the commitment step in the retinoic acid-induced differentiation of F9 mouse teratocarcinoma cells, at least in part, via forming complexes with retinoic acid receptor and activation transcription factor-2 (ATF-2). In addition, antisense oligonucteotide treatment of embryonic mouse lung explants suggests that Rcd1 also plays a role in retinoic acid-controlled lung development. [ABSTRACT FROM AUTHOR]

Reports on the cellular events occurring outside the nervous system that are mediated by semaphorins, their receptors and associated molecules. Information on semaphorins in axon guidance; Data on functional receptor complexes for semaphorins; Non-neural functions of semaphorin signaling; Lung development and semaphorin signaling.

Background: In oral lichen planus (OLP), destruction of the basal cell layer, which is one of the characteristic histological features, is seen and many changes in cell proliferation, cell repair and cell death occur in the injured mucosal epithelium.Methods: We studied mucosal tissues from 19 patients of OLP and 10 controls, with immunohistochemistry for Ki-67, p53, cyclin dependent kinase inhibitors (CDKI) and cyclins. Mitotic count was calculated. TUNEL assay was also performed for evaluation of apoptotic cell death.Results: Mitotic count, Ki-67 and cyclin D1 labeling indices in the basal and parabasal layers of OLP mucosa were elevated in comparison with those of controls. p53, p21Cip1 and TUNEL indices of OLP mucosa were also increased.Conclusions: These complex changes, which concomitantly occur in the injured mucosal epithelium, could contribute to the development and maintenance of characteristic mucosal epithelial architectures seen in OLP. [ABSTRACT FROM AUTHOR]

Abstract Background: M1 prostate cancer, which is invasive, is usually associated with a serum level of prostate-specific antigen (PSA) greater than 10 ng/mL, but cases are occurring where the serum PSA level is less than this. The present study investigated the clinical and pathologic characteristics of these cases of M1 prostate cancer. Methods: Between April 1989 and March 1998, 167 cases of M1 prostate cancer were diagnosed by transrectal needle biopsy and eight of these with a serum PSA level less than 10 ng/mL were investigated. The patients' ages ranged from 57 to 79 years (median, 73) and the serum PSA levels ranged from less than 4.0 to 9.8 ng/mL. In all cases except one, the distal metastasis was to bones only. All cases had received hormonal therapy as the initial therapy. Immunostaining of PSA, chromogranin A, neuron-specific enolase, carcinoembryonic antigen and vimentin were performed in five of the eight cases. Results: Four cases were poorly differentiated, two were undifferentiated, one was a mixture of poorly differentiated and undifferentiated and one case was moderately differentiated. Of the five cases in the immunohistochemical study, three cases with an undifferentiated carcinoma component showed negative staining reactions for PSA and all cases were positive for carcinoembryonic antigen. Four of the patients died of prostate cancer. In two of these four cases, hormonal therapy was ineffective, but systemic chemotherapy and irradiation therapy had been moderately effective. The overall 3-year survival rate was 33.3%. Conclusions: The cases of M1 prostate cancer with a serum PSA less than 10 ng/mL are almost always poorly differentiated or undifferentiated and have a poor prognosis compared with the usual M1 prostate cancer. Because hormonal therapy is ineffective in these cases, systemic chemotherapy and irradiation therapy should be chosen as the initial therapy. [ABSTRACT FROM AUTHOR]

Background Previously, we reported that Sema3A, one of the secreted repulsive axon guidance molecules, CRMP (collapsin response mediator protein)-2, a putative intracellular signalling molecule for Sema3A and Sema3A receptor neuropilin-1 are expressed in the developing lung. Sema3A inhibits branching morphogenesis of embryonic lung in organ culture. Results We examined the gene expression of Sema3A, Sema3C, Sema3F and their receptors, NP-1, NP-2 and plexin-A1 by in situ hybridization. Transcripts of all six genes were detected in mouse lung from embryonic day E11.5 to E17.5, and displayed highly specific spatiotemporal distributions. The distribution of the receptor genes was detected in patterns which were consistent with known receptor usage of the semaphorins. In contrast to Sema3A, we found that the other class 3 semaphorins, Sema3C and Sema3F, stimulated branching morphogenesis. This stimulatory effect of Sema3C or Sema3F was accompanied by a moderate increase in the incorporation of bromodeoxyuridine (BrdU) into DNA in the terminal epithelial cells. Conclusion The coordinated expression patterns of different semaphorins and their receptors, together with the specific activities affecting branching morphogenesis, suggest that the semaphorins act as both positive and negative regulators of branching morphogenesis in the developing lung. [ABSTRACT FROM AUTHOR]

Abstract A case of primary signet-ring cell carcinoma of the urinary bladder that was found to have induced renal failure is the second such case reported in the world. Primary signet-ring cell carcinoma of the urinary bladder is a rare histologic variant of adenocarcinoma. The patient died of distant metastasis 8 months after undergoing total cystectomy. The neoplasm had a high stage at diagnosis, so the prognosis was very poor. To improve the prognosis, earlier diagnosis and establishing a regimen of chemotherapy is necessary. [ABSTRACT FROM AUTHOR]

We report a case of malignant phyllodes tumor of the prostate which is the eleventh reported case in the world. Phyllodes tumor of the prostate is extremely rare and histologically resembles mammary phyllodes tumor. Phyllodes tumor of the prostate is classified into benign, borderline and malignant, but health professionals should carefully follow up the borderline cases in case they take a malignant clinical course. This case was the first to be treated by pre- and postoperative radiation therapy. Although the patient had a slight response to radiation therapy, he eventually developed metastasis. Because malignant phyllodes tumor of the prostate is a very aggressive tumor, people with the condition should undergo systemic chemotherapy as adjuvant therapy. [ABSTRACT FROM AUTHOR]

Myoepithelioma of the lacrimal gland is extremely rare and only four cases, one of which was malignant, have been reported in detail. The present report describes a case of lacrimal gland myoepithelioma in a Japanese male with histological features suggestive of potentially malignant transformation. The excised tumor consisted of two components, a central nodular component and a peripheral component surrounding the former. These components were separated by a fibrous tissue. Microscopically, both components were comprised almost entirely of spindle-shaped cells, but with some epithelioid cells containing glycogen granules. Extracellular spaces in the peripheral component were filled with eosinophilic materials with the occasional crystalloid structures, which were immunoreactive for collagen type I. Neoplastic cells were immunoreactive focally for vimentin and S-100, but negative for cytokeratins, epithelial membrane antigen, muscle actin, smooth muscle actin, desmin, myosin, and glial fibrillary acidic protein. The neoplastic cells in the central component showed nuclear pleomorphism and atypia with a higher frequency of mitotic figures, and higher labelings of proliferation markers than those in the peripheral component. Neither invasion, necrosis, nor hemorrhage was observed in the tumor. From these findings we proposed a diagnosis of potentially malignant myoepithelioma. [ABSTRACT FROM AUTHOR]

Twenty-four specimens of squamous cell carcinoma of the tongue were immunostained for heat shock proteins (HSPs) to reveal differences in stainability among normal epithelium, dysplasia and carcinoma and to clarify the prognostic significance of HSPs in comparison with survival period, clinical stage, lymph node metastasis, histological grade, and p53 immunostaining. Normal epithelium was positively stained in the suprabasal layer for HSP60 and HSP70, but was negative for HSP27 and HSP90. Dysplastic lesions were positive for HSP27, HSP70 and HSP90, but stained variously for HSP60. In squamous cell carcinoma, the cytoplasm of suprabasal tumor cells was often positive for HSP27 and HSP90 (18/24, 17/24, respectively). Although HSP immunohistochemistry has revealed changes in HSP expression during tumorigenesis of squamous epithelium of the tongue, there was no correlation between HSP staining and survival period, stage, lymph node metastasis, histological grade or p53 immunostaining. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the characteristics of recent male and female patients diagnosed with interstitial cystitis (IC), then investigated which therapy was chosen by the attending urologist. Methods: Materials were 282 IC patients diagnosed and treated during the past 3 years (sampling from Japanese IC database). Gender, age, medical history and predominant symptoms were investigated. In addition, we investigated the interval before a diagnosis was established. In laboratory findings, we investigated voided volume, urinalysis findings and cystoscopic findings. Regarding therapy, we investigated which therapy was chosen as the first line. Results: The gender ratio was about 1.0:5.6 (male : female). Regarding age distribution, patients in their 60s were the most frequent (65 cases, 31.3%). The interval before diagnosis of IC was 36.5 months on average (1–360 months). Regarding medical history, intrapelvic surgery was the most common and repeated urinary tract infection was next. The most frequent symptom was urinary frequency (295 cases, 98.3%). Urinary urgency was noted in 186 cases (62%) and supra-pubic pain was noted in 125 cases (41.6%). The once voided volume was 104.3 mL on average (50–200 mL). The most common cystoscopic finding was glomerulation (158 cases). Ulcer was present in only 19 cases. The most widely carried out therapy was hydrodistension (208 cases, 67.9%). Oral suplatast tosilate (197 cases, 65.6%), antihistamine (77 cases, 25.6%) and intravesical dimethylsulfoxide (69 cases, 23%) followed. Conclusions: Regarding characteristics, the age distribution was older than other countries. The most frequent symptom was urinary frequency. Oral suplatast tosilate was one of the popular therapies in Japan. [ABSTRACT FROM AUTHOR]

We evaluated the storage stability of powder containing naked plasmid DNA (pDNA) and hyaluronic acid (HA) or mannitol (Man) prepared by the spray-freeze-drying technique, through which we have reported high gene expression without any gene vectors. The powders composed of 5–10-µm porous particles and showing excellent dispersion were stored for 12 months under three storage conditions: 5 °C/Dry, 25 °C/Dry, and 25 °C/75% relative humidity. The humidified powders lost their porous shape within 1 week and were not suitable for inhalation characterization. On the other hand, the powders under dry conditions maintained high inhalation characteristics and pDNA integrity for 12 months. We administered the powders to the lungs of mice. The naked pDNA in HA powder showed significantly higher gene expression compared with that in Man powder and a pDNA-polyethylenimine complex solution. The gene expression of pDNA/HA powder was maintained for 12 months. These results suggest that powder containing naked pDNA is stable on storing under appropriate dry conditions and the naked pDNA/HA powder shows effective pulmonary gene expression. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate anatomical resection (AR) versus non-AR for primary solitary hepatocellular carcinoma (HCC) with predicted microscopic vessel invasion (MVI) and/or microscopic intrahepatic metastasis (MIM). Methods: This retrospective study included 358 patients who underwent hepatectomy and had no evidence of MVI and/or MIM on preoperative imaging. The predictors of MVI and/or MIM were identified. The AR group (n = 222) and the non-AR group (n = 136) were classified by number of risk factor, and the survival rates were compared. Results: Microscopic vessel invasion and/or MIM were identified in 81 (22.6%) patients. A multivariate analysis showed that high des-gamma-carboxy prothrombin concentration [odds ratio (OR) 3.35], large tumor size (OR 3.16), and high aspartate aminotransferase concentration (OR 2.13) were significant predictors. The 5-year overall survival (OS) in the patients with zero, one, two, and three risk factors were 97.4%, 73.5%, 71.5%, and 65.5%, respectively. The OS of AR is superior to that of non-AR only in patients with one or two risk factors. Conclusion: The present findings suggest that AR should be performed for patients with one or two risk factors, and that AR may prevent recurrence, as these patients are at risk of having MVI and/or MIM. [ABSTRACT FROM AUTHOR]

The original sepal color of Hydrangea macrophylla is blue, although it is well known that sepal color easily changes from blue through purple to red. All the colors are due to a unique anthocyanin, 3-O-glucosyldelphinidin, and both aluminum ion (Al3+) and copigments, 5-O-caffeoyl and/or 5-O-p-coumaroylquinic acid are essential for blue coloration. A mixture of 3-O-glucosyldelphinidin, 5-O-acylquinic acid, and Al3+ in a buffer solution at pH 4 produces a stable blue solution with visible absorption and circular dichroism spectra identical to those of the sepals, then, we named this blue pigment as 'hydrangea blue-complex'. The hydrangea blue-complex consists of 3-O-glucosyldelphinidin, Al3+, and 5-O-acylquinic acid in a ratio 1:1:1 as determined by the electrospray ionization time-of-flight mass spectrometry and nuclear magnetic resonance spectra. To map the distribution of hydrangea blue-complex in sepal tissues, we carried out cryo-time-of-flight secondary ion mass spectrometry analysis. The spectrum of the reproduced hydrangea blue-complex with negative mode-detection gave a molecular ion at m/z = 841, which was consistent with the results of ESI-TOF MS. The same molecular ion peak at m/z = 841 was detected in freeze-fixed blue sepal-tissue. In sepal tissues, the blue cells were located in the second layer and the mass spectrometry imaging of the ion attributable to hydrangea blue-complex overlapped with the same area of the blue cells. In colorless epidermal cells, atomic ion of Al3+ was hardly detected and potassium adduct ion of 5-O-caffeoyl and/or 3-O-acylquinic acid were found. This is the first report about the distribution of aluminum, potassium, hydrangea blue-complex, and copigment in sepal tissues and the first evidence that aluminum and hydrangea blue-complex exist in blue sepal cells and are involved in blue coloration. [ABSTRACT FROM AUTHOR]

The preoperative accurate diagnosis is difficult in the patients with intraductal papillary mucinous neoplasm (IPMN). The aim of the present study was to elucidate the roles of systemic inflammation responses and nutritional status indexes in IPMN. High-grade dysplasia was classified as a malignant neoplasm in the study. We retrospectively reviewed 155 patients who underwent pancreatectomy. The correlation between the clinical factors and several indexes of a systemic inflammation response and nutritional status was analyzed. Among the biomarkers, prognostic nutritional index (PNI) value of malignant IPMN patients was significantly lower than that of benign IPMN patients (P = 0.023), whereas PNI was not significant predictor for malignant IPMN. The multivariate analysis showed that a PNI < 43.5 (odds ratio [OR] 16.1, 95% CI 1.88–138.5, P = 0.011) and a carbohydrate antigen (CA) 19–9 level > 22.5 U/mL (OR 6.64, 95% CI 1.73–25.6, P = 0.006) were significant independent predictors of the presence of lymph node metastasis (LNM). Our scoring system developed based on these two factors. Patients with a score of 0 had no LNM and zero disease-related death. The present study suggested the roles of PNI on the IPMN patients who undergo curative pancreatectomy. [ABSTRACT FROM AUTHOR]

The blue sepal color of hydrangea is due to a metal complex anthocyanin composed of 3-O-glucosyldelphinidin (1) and an aluminum ion with the co-pigments 5-O-caffeoylquinic acid (2) and/or 5-O-p-coumaroylquinic acid (3). The three components, namely anthocyanin, Al3+ and 5-O-acylquinic acids, are essential for blue color development, but the complex is unstable and only exists in an aqueous solution. Furthermore, the complex did not give analyzable NMR spectra or crystals. Therefore, many trials to determine the detailed chemical structure of the hydrangea-blue complex have not been successful to date. Instead, via experiments mixing 1, Al3+ and 2 or 3 in a buffered solution at pH 4.0, we obtained the same blue solution derived from the sepals. However, the ratio was not stoichiometric but fluctuated. To determine the composition of the complex, we tried direct observation of the molecular ion of the complex using electrospray-ionization mass spectrometry. In a very low-concentration buffer solution (2.0 mM) at pH 4.0, we reproduced the hydrangea-blue color by mixing 1, 2 and Al3+ in ratios of 1:1:1, 1:2:1 and 1:3:1. All solution gave the same molecular ion peak at m/z = 843, indicating that the blue solution has a ratio of 1:1:1 for the complex. By using 3, the observed mass number was m/z = 827 and the ratio of 1, 3 and Al3+ was also 1:1:1. A mixture of 1, 3-O-caffeoylquinic acid (4) and Al3+ did not give any blue color but instead was purple, and the intensity of the molecular ion peak at m/z = 843 was very low. These results strongly indicate that the hydrangea blue-complex is composed of a ratio of 1:1:1 for 1, Al3+ and 2 or 3. [ABSTRACT FROM AUTHOR]

Background: Right hepatectomy with caudate lobectomy (RHx) is considered an appropriate procedure for Bismuth type I/II perihilar cholangiocarcinoma in terms of its anatomical and oncological aspect. However, validity of left hepatectomy with caudate lobectomy (LHx) concomitant with arterial resection and reconstruction (AR) is not fully evaluated.Methods: The patients who underwent surgical resection for Bismuth type I/II perihilar cholangiocarcinoma between 2002 and 2013 were studied. The standard procedure for Bismuth type I/II cholangiocarcinoma in the institute was RHx, while in patients who had insufficient functional reserve of the left liver, LHx was selected, irrespective of the necessity of AR. The clinicopathologic and perioperative outcomes after LHx + AR were compared with those after RHx.Results: The surgical procedures comprised LHx + AR in 12 and RHx in 24. The left liver volume and left liver functional reserve were significantly lower with LHx + AR than with RHx (left liver volume: 28.0 vs. 33.7%, p = 0.026; estimated indocyanine green clearance of the left liver: 0.036 vs. 0.046, p < 0.001). The rate of surgical morbidity was almost identical between the two procedures. No arterial reconstruction-related complications occurred. The overall 3- and 5-year survival rates and median survival time were 66.7%, 41.7% and 44 months for LHx + AR and 70.8%, 49.0% and 57 months for RHx (p = 0.640).Conclusion: LHx + AR for Bismuth type I/II perihilar cholangiocarcinoma is considered to be a valid alternative to RHx in patients with an insufficient left liver functional reserve. [ABSTRACT FROM AUTHOR]

Abstract Acenaphthylene units work as a useful platform for the synthesis of polycyclic aromatic hydrocarbons (PAH). Three 1,2-diarylacenaphthylene derivatives (9-phenanthryl, 7- t -butyl-2-pyrenyl and 2-naphthyl) were prepared by Suzuki-Miyaura coupling of 1,2-dibromoacenaphthylene with the corresponding boronic acids and ester. The Scholl reaction of the phenanthryl derivative affords a donor-acceptor type fluoranthene derivative possessing a hemi -coronene structure by forming two C C bonds between phenanthryl groups. The reaction of the pyrenyl derivative allows one C C bond formation to give a helicene-type fluoranthene derivative. The reaction of the naphthyl derivative provides an asymmetric fluroranthene derivative having an anthracene unit accompanied with one C C bonding reaction, while a photochemical cyclization followed by dehydroaromatization reaction of the compound gives a symmetric fluoranthene derivative with a [5]helicene structure. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Background: With aging populations increasing in developed countries, the prevalence of elderly patients with hepatocellular carcinoma (HCC) is expected to rise. The aim of this study was to determine the short- and long-term outcomes of HCC surgery in elderly patients (≥75 years) using propensity score matching. Methods: The study group included 421 patients who underwent hepatectomy as their initial treatment with curative intent. The patients were divided into elderly (n = 111) and non-elderly (n = 310) groups. We applied propensity score matching – taking into consideration patient background, blood examination, and tumor factors – to minimize the effect of potential confounders. We then compared the results before and after the propensity matching. Results: Before propensity matching, the elderly group included significantly more patients with a high American Society of Anesthesiologists physical status (p < 0.001). In addition, they were taking antihypertensive drugs or an anticoagulant (both p < 0.001). The severe postoperative complications and the overall survival rates for these elderly patients were significantly poorer than for the non-elderly patients (p = 0.015 and p = 0.030, respectively). We then chose 70 patients from each group for whom the preoperative confounding factors were balanced and compared the two groups. The factors identified before matching (severe complications and overall survival rates) were no longer relevant, i.e. there were no significant differences between the two groups. Conclusion: Hepatectomy for HCC in elderly patients is justified. [ABSTRACT FROM AUTHOR]

Background and aim: Previous studies have shown that microscopic vessel invasion (MVI) occurs in hepatocellular carcinoma (HCC) with a treatment history due to its poorer malignant behavior in comparison with primary HCC. The aim of the present study was to determine the predictors of MVI and overall survival in HCC patients with a treatment history.Methods: This retrospective study included 580 patients who underwent hepatectomy and whose preoperative imaging showed no evidence of macroscopic vessel invasion. The patients were classified into two groups: primary HCC (n = 425) and HCC with a treatment history (n = 155). MVI was defined as the presence of either microscopic portal vein invasion or venous invasion, which was invisible on preoperative imaging.Results: MVI was identified in 34 (21.9%) patients with a treatment history. A multivariate analysis showed that a high des-gamma-carboxy prothrombin (odds ratio [OR] 5.16, P = 0.002) and a large tumor diameter (OR 2.57, P = 0.030) were the significant predictor of MVI in HCC with a treatment history. Moreover, the presence of MVI (hazard ratio [HR] 2.27, P = 0.001) and tumor diameter >27 mm (HR 2.04, P = 0.006) remained significant predictors of the overall survival in HCC with a treatment history. The tumor diameter cutoff value for predicting MVI (27 mm) in HCC with a treatment history was smaller than in primary HCC (37 mm).Conclusions: The presence of MVI was a significant predictor in the HCC patients with a treatment history. The tumor diameter is an important factor that can be used to predict the presence of MVI, especially in HCC with a treatment history. [ABSTRACT FROM AUTHOR]

Tumor‐initiating cells are major drivers of chemoresistance and attractive targets for cancer therapy, however, their identity in human pancreatic ductal adenocarcinoma (PDAC) and the key molecules underlying their traits remain poorly understood. Here, we show that a cellular subpopulation with partial epithelial‐mesenchymal transition (EMT)‐like signature marked by high expression of receptor tyrosine kinase‐like orphan receptor 1 (ROR1) is the origin of heterogeneous tumor cells in PDAC. We demonstrate that ROR1 depletion suppresses tumor growth, recurrence after chemotherapy, and metastasis. Mechanistically, ROR1 induces the expression of Aurora kinase B (AURKB) by activating E2F through c‐Myc to enhance PDAC proliferation. Furthermore, epigenomic analyses reveal that ROR1 is transcriptionally dependent on YAP/BRD4 binding at the enhancer region, and targeting this pathway reduces ROR1 expression and prevents PDAC growth. Collectively, our findings reveal a critical role for ROR1high cells as tumor‐initiating cells and the functional importance of ROR1 in PDAC progression, thereby highlighting its therapeutic targetability. Synopsis: Cancer cell diversity and contribution of tumor‐initiating cells to pancreatic ductal adenocarcinoma (PDAC) progression remain poorly defined. In this work, single‐cell RNA sequencing and functional analyses uncovered targetable tumor‐initiating cells in PDAC. Heterogeneous tumor cells in PDAC arise from a subpopulation with partial EMT signature characterized by high expression of ROR1.Intratumoral ROR1high cells are tumor‐initiating cells with increased tumorigenic capacity.ROR1 functionally promotes PDAC tumor growth, relapse after chemotherapy, and metastasis.ROR1 induces the expression of AURKB via activation of AKT/c‐Myc/E2F signaling, thereby enhancing PDAC proliferation.ROR1 transcription is dependent on the YAP/BRD4 axis. [ABSTRACT FROM AUTHOR]

Background: The serum antibody to hepatitis B core antigen (HBcAb) is considered a risk factor of liver carcinogenesis. This study aimed to reveal whether HBcAb status is a prognostic factor after hepatectomy is performed for treating hepatocellular carcinoma (HCC). Methods: This retrospective study enrolled 272 patients who underwent hepatectomy as the initial treatment for HCC and who were followed up over 5 years after surgery. The types of HCC were classified into the following 3 types according to the hepatitis virus infection status and the patients without hepatitis virus infection non-B non-C HCC (NBNC-HCC) were further classified into 2 groups. Results: There is no novel finding as a result of the comparison made among hepatitis virus status. Of 90 patients (33.1%) with NBNC-HCC, 10 patients were excluded because the preoperative HBcAb status was not measured. There were 51 patients (63.8%) who were HBcAb-positive and 29 patients (36.2%) who were HBcAb-negative. In multivariate analysis, the presence of HBcAb-negative (hazard ratio 2.10, 95% CI 1.09-4.03, p = 0.026) remained as significant independent risk factors for recurrence in NBNC-HCC. Conclusions: This study shows that the HBcAb-positive is rather a favorable predictor for recurrence after curative resection in NBNC-HCC. [ABSTRACT FROM AUTHOR]

Background: Gastroenterostomy and stent placement are the most common palliative procedures for patients with a gastric outlet obstruction caused by advanced pancreatic adenocarcinoma. Gastroenterostomy is regarded as the optimum treatment for patients in whom a longer survival is expected, while stent placement is preferred for patients whose survival is likely to be relatively short. However, prognosis of such patients has not been fully evaluated. Methods: This study included patients undergoing gastroenterostomy or duodenal stent placement for gastric outlet obstruction caused by advanced pancreatic adenocarcinoma between 2002 and 2015. Prognostic factors found to be significant based on a multivariate analysis were given a prognostic score according to their hazard ratios (HR). The overall survivals stratified according to the total prognostic score were compared. Results: The median survival time of all cohorts was 4.2 months. The multivariate analyses demonstrated a neutrophil-to-lymphocyte ratio (NLR) ≥ 4 (HR = 4.01, p < 0.001), presence of liver metastases (HR = 1.90, p = 0.002), and presence of cancer pain (HR = 2.08, p < 0.001) to be significant prognostic factors. Regarding the HR, NLR ≥ 4, liver metastases and cancer pain were subsequently scored as 2, 1, and 1, respectively. The median survival time was 9.4 months in patients with a score of 0 or 1 and 3.3 months in patients with a score of 2-4, respectively. Conclusion: The scoring system clearly demonstrates the patient survival. Patients with scores of 0 or 1 are favorable candidates for gastroenterostomy, while patients with scores of 2-4 are candidates for stent placement. [ABSTRACT FROM AUTHOR]

Purpose: To establish the optimal cut-off value of the preoperative prognostic nutritional index (PNI) for prognosis according to the Tumor Node Metastasis (TNM) stage of hepatocellular carcinoma (HCC) after curative resection. Methods: This retrospective study reviewed the records of 375 patients. The optimal cut-off value of the PNI was established according to the TNM stage, and overall survival was compared between the low and high PNI groups. Results: The optimal cut-off value of the PNI decreased with increasing TNM stage, with 52, 47, and 43 patients having stage I, II, and III HCC, respectively. A low preoperative PNI predicted a poorer overall survival than did a high PNI for stage I ( P < 0.001) and II ( P = 0.002), but not stage III disease ( P = 0.052). Multivariate analysis revealed that the preoperative PNI was an independent predictor of overall survival for stage I and II HCC (hazard ratios: 6.96 and 3.57, P = 0.001 and P = 0.001, respectively). Conclusions: The findings of this study show that the optimal cut-off value for the PNI for prognosis differs among the TNM stages and that the preoperative PNI is a favorable prognostic factor for stage I HCC. [ABSTRACT FROM AUTHOR]

The confirmation of target expression in tissues is a prerequisite for molecular-targeted therapy. However, difficulties are sometimes associated with the production of appropriate antibodies against receptors. We herein developed a ligand derivative dye for the staining of receptors. The somatostatin receptor (sstr) was selected as the target and FITC-octreotate as the detective agent. We performed a blot analysis to detect sstr in the transfer membrane. The sstr2 recombinant protein or cell lysate from a small cell lung carcinoma cell line (H69) was boiled and loaded onto SDS-PAGE, and the proteins were transferred to a membrane. Even after denaturing processes, FITC-octreotate still bound sstr on the membrane. Furthermore, FITC-octreotate depicted the expression of sstr in formalin-fixed and paraffin-embedded (FFPE) sections, a method that we named ligand derivative staining (LDS). The accuracies of immunostaining and LDS were compared at the points of the detection of sstr using FFPE sections of 30 neuroendocrine tumor specimens. The sensitivity of LDS was 81.8%, while those of immunostaining using anti-sstr2 and sstr5 antibodies were 72.7% and 63.6%, respectively. Thus, LDS appears to be superior to immunostaining. A ligand derivative may be used as a substitute for antibodies, and has the potential to support economical, simple, and accurate detection methods. [ABSTRACT FROM AUTHOR]

Background: The survival impact of distal pancreatectomy (DP) with celiac axis resection for locally advanced pancreatic body/tail cancer remains unclear. Methods: A total of 16 patients underwent DP with celiac axis resection, while 76 underwent standard DP for pancreatic body/tail cancer. The indications for DP with celiac axis resection included: (a) tumor invasion of either the celiac axis or common hepatic artery or both [CA/CHA (+)] and (b) tumor invasion of the root of the splenic artery, which is difficult to dissect without securing an adequate surgical margin [CA/CHA (−)]. Results: DP with celiac axis resection presented longer operative time and greater amount of blood loss than DP. The median survival time was 17.5 months in the DP with celiac axis resection group and 43.1 months in the DP group ( p = 0.040). Among the patients who underwent DP with celiac axis resection, the median survival time was 35.1 months in the CA/CHA (−) group and 13.2 months in the CA/CHA (+) group ( p = 0.001). Comparing the patients undergoing standard DP and DP with celiac axis resection with a CA/CHA (−) status, there were no significant differences in either disease-free or overall survival times. The CA19-9 value, CA/CHA (+) status, and microscopic venous infiltration were revealed independent significant prognostic factors. Conclusions: DP with celiac axis resection should therefore be indicated in patients with a CA/CHA (−) status. However, it is difficult to justify the use of DP with celiac axis resection in patients with CA/CHA (+) status due to the poor survival. [ABSTRACT FROM AUTHOR]

Sirtuins (SIRT1–7 in mammals) are evolutionarily conserved nicotinamide adenine dinucleotide-dependent lysine deacetylases/deacylases that regulate fundamental biological processes including aging. In this study, we reveal that male Sirt7 knockout (KO) mice exhibited an extension of mean and maximum lifespan and a delay in the age-associated mortality rate. In addition, aged male Sirt7 KO mice displayed better glucose tolerance with improved insulin sensitivity compared with wild-type (WT) mice. Fibroblast growth factor 21 (FGF21) enhances insulin sensitivity and extends lifespan when it is overexpressed. Serum levels of FGF21 were markedly decreased with aging in WT mice. In contrast, this decrease was suppressed in Sirt7 KO mice, and the serum FGF21 levels of aged male Sirt7 KO mice were higher than those of WT mice. Activating transcription factor 4 (ATF4) stimulates Fgf21 transcription, and the hepatic levels of Atf4 mRNA were increased in aged male Sirt7 KO mice compared with WT mice. Our findings indicate that the loss of SIRT7 extends lifespan and improves glucose metabolism in male mice. High serum FGF21 levels might be involved in the beneficial effect of SIRT7 deficiency. [ABSTRACT FROM AUTHOR]

Focuses on clinical symptom scales for interstitial cystitis for diagnosis and for following the course of the disease. Quantification of patients; Measurement of treatment outcome.

Background: Multiple mutation (MM) within a single gene has recently been reported as a mechanism involved in carcinogenesis. The present study investigated the clinical significance of MMs in hepatocellular carcinoma (HCC).Methods: Two hundred twenty-three surgically resected HCCs were subjected to gene expression profiling and whole-exome sequencing.Results: MMs in individual genes were detected in 178 samples (MM tumors: 79.8%). The remaining samples all carried a single mutation (SM tumors: 20.2%). Recurrence-free survival in the MM group was significantly worse in comparison to the SM group (P = 0.012). A Cox proportional hazard analysis revealed that MM tumor was an independent predictor for worse a prognosis (hazard ratio, 1.72; 95% confidence interval, 1.01-3.17; P = 0.045). MMs were frequently observed across in various genes, especially MUC16 (15% of samples had at least one mutation in the gene) and CTNNB1 (14%). Although the MUC16 mRNA expression of MUC16 wild-type and MUC16 SM tumors did not differ to a statistically significant extent, the expression in MUC16 MM tumors was significantly enhanced in comparison to MUC16 SM tumors (P < 0.001). In MUC16, MMs were associated with viral hepatitis, higher tumor marker levels and vascular invasion. The MUC16 MMs group showed significantly worse recurrence-free survival in comparison to the MUC16 SM group (P = 0.022), while no significant difference was observed between the MUC16 SM group and the MUC16 wild-type group (P = 0.324).Conclusions: MM was a relatively common event that may occur selectively in specific oncogenes and is involved in aggressive malignant behavior. [ABSTRACT FROM AUTHOR]

Although a soft pancreas is a widely-accepted reliable risk factor for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD), there is no established preoperative evaluation of pancreatic texture. Two hundred thirty-seven patients who underwent PD with histological pancreatic assessment were retrospectively enrolled. The degree of fibrosis and fatty infiltration was scored histologically as seven grades and five grades, respectively. Computed tomography (CT) attenuation of the pancreas was measured on preoperative unenhanced CT images. Correlations between the CT attenuation of the pancreas and the histological pancreatic findings, and the development of POPF were analyzed. The fibrosis grade was significantly higher for hard pancreas than for soft pancreas (p < 0.001), whereas the fatty infiltration grade was similar between the two types (p = 0.161). CT attenuation of the pancreas was inversely correlated with both fibrosis grade (Spearman's rank correlation coefficient ([r] = −0.609, p < 0.001) and fatty infiltration grade (r = −0.382, p < 0.001). Multivariate analysis showed that body mass index ≥25 kg/m2 (odds ratio [OR]: 5.64, p < 0.001) and fibrosis grade ≤2 (OR: 18.0, p < 0.001) were independent risk factors for clinically significant POPF. Histological pancreatic texture can be evaluated with CT attenuation and might be helpful in preoperatively predicting the development of POPF after PD. [ABSTRACT FROM AUTHOR]

Decomposition of [Me 3 PrN][(CF 3 SO 2 ) 2 N], a typical room-temperature ionic liquid used for electrochemical devices, in subcritical and supercritical water was investigated with the aim of developing a technique to recover the fluorine component from ionic liquid wastes. When the reaction was carried out in pure subcritical water at 342 °C for 6 h, 99% of the anionic moiety, [(CF 3 SO 2 ) 2 N] − , remained, and the F − yield was only 1%. In contrast, in the presence of zerovalent iron, the yield of F − increased to 52%. Although the reactivity of FeO toward the anionic moiety in subcritical water was lower than that of zerovalent iron, the reactivity of FeO increased dramatically when the water was heated to the supercritical state, under which conditions FeO underwent in situ disproportionation to form zerovalent iron and Fe 3 O 4 . Specifically, when the reaction was carried out at 376 °C for 18 h, the F − yield reached 90%, which was the highest yield obtained under the tested conditions. In addition, under these conditions, the formation of environmentally undesirable CF 3 H was suppressed. [ABSTRACT FROM AUTHOR]

Purpose: Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are prognostic factors for hepatocellular carcinoma (HCC). The impact of these tumor markers in recurrent HCC on the prognosis remains to be fully elucidated. Methods: Two hundred and seventeen patients whose AFP and DCP levels were measured at recurrence were enrolled in the present study. AFP levels >10 ng/mL and DCP levels ≥40 mAU/mL were defined as AFP positive (AFP+) and DCP positive (DCP+), respectively. The patterns of tumor markers were scored as AFP−/DCP−, 0; AFP+/DCP− or AFP−/DCP+, 1 and AFP+/DCP+, 2. Results: The median survival period after recurrence in patients with a score of 2 (26.6 months) was significantly lower than that in patients with scores of 1 or 0 (43.5 months, P < 0.01; 75.3 months, P < 0.01, respectively). A multivariate analysis showed that a tumor marker score of 2 at recurrence was an independent predictor for poor survival after recurrence (hazard ratio 2.12, P = 0.03). The prognosis after recurrence in the patients with a decreased tumor maker score was significantly better than that in the patients with no change in the tumor marker score compared to the primary surgery ( P = 0.048). Conclusions: The present study shows that measurements of both AFP and DCP are useful for predicting the prognosis of recurrent HCC. [ABSTRACT FROM AUTHOR]

Right hepatectomy occasionally requires portal vein resection (PVR) and causes postoperative portal vein thrombosis (PVT). A total of 247 patients who underwent right hepatectomy were evaluated using a three-dimensional analyzer to identify the morphologic changes in the portal vein (PV). The patients' characteristics were compared between the PVR group (n = 73) and non-PVR group (n = 174), and risk factors for PVT were investigated. The PVR group were subdivided into the wedge resection (WR) group (n = 38) and segmental resection (SR) group (n= 35). Postoperative PVT occurred in 20 patients (8.1%). Multivariate analyses in all patients revealed that postoperative left PV diameter/main PV diameter (L/M ratio) <0.56 (odds ratio [OR] 4.00, p = 0.009) and PVR (OR 3.31, p = 0.031) were significant risk factors for PVT. In 73 patients who underwent PVR, PVT occurred in 14 (19%) and WR (OR 11.5, p = 0.005) and L/M ratio <0.56 (OR 5.51, p = 0.016) were significant risk factors for PVT. PVR was one of the significant risk factors for PVT after right hepatectomy. SR rather than WR may be recommended for preventing PVT. [ABSTRACT FROM AUTHOR]

Background and aim: Several papers have shown that preoperative inflammation-based prognostic scores and/or immunonutritional status are associated with survival in patients with hepatocellular carcinoma (HCC). However, the validity of prognostic factors of these scores remains controversial. This study aimed to validate the power of prognostic scores based on the preoperative inflammatory and immunonutritional indices of patients who underwent hepatectomy for HCC with curative intent. Methods: Clinicopathological parameters and inflammation-based prognostic scores and immunonutritional status, including the Glasgow Prognostic Score, neutrophil to lymphocyte ratio (NLR), and prognostic nutritional index (PNI), were retrospectively analyzed to identify the predictors of overall and recurrence-free survival in 256 patients. Results: In multivariate analysis, NLR was an independent prognostic factor for overall, and recurrence-free survival (hazard ratio [HR] 2.59, 95 % confidence interval [CI] 1.56-4.31, P < 0.001, and HR 2.11, 95 % CI 1.44-3.11, P < 0.001, respectively). Additionally, PNI was an independent predictor of overall survival (HR 2.01, CI 1.21-3.36, P = 0.007). Conclusions: The present study shows that the NLR and PNI based on preoperative inflammatory and immunonutritional indices are predictors of overall survival in patients who undergo hepatectomy for HCC with curative intent. [ABSTRACT FROM AUTHOR]