Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407213835

CiNii Research

Language：Japanese  

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

Actomyosin contractility regulates various cellular processes including proliferation and differentiation while dysregulation of actomyosin activity contributes to cancer development and progression. Previously, we have reported that actomyosin-generated tension at adherens junctions is required for cell density-dependent inhibition of proliferation of normal skin keratinocytes. However, it remains unclear how actomyosin contractility affects the hyperproliferation ability of cutaneous squamous cell carcinoma (cSCC) cells. In this study, we find that actomyosin activity is impaired in cSCC cells both in vitro and in vivo. External application of tensile loads to adherens junctions by sustained mechanical stretch attenuates the proliferation of cSCC cells, which depends on intact adherens junctions. Forced activation of actomyosin of cSCC cells also inhibits their proliferation in a cell-cell contact-dependent manner. Furthermore, the cell cycle arrest induced by tensile loading to adherens junctions is accompanied by epidermal differentiation in cSCC cells. Our results show that the degree of malignant properties of cSCC cells can be reduced by applying tensile loads to adherens junctions, which implies that the mechanical status of adherens junctions may serve as a novel therapeutic target for cSCC.

DOI： 10.3389/fcell.2021.728383

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Long-standing chronic pancreatitis is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Interleukin-1β (IL-1β) has been associated in PDAC with shorter survival. We employed murine models to investigate the mechanisms by which IL-1β and chronic pancreatitis might contribute to PDAC progression. DESIGN: We crossed LSL-Kras +/G12D;Pdx1-Cre (KC) mice with transgenic mice overexpressing IL-1β to generate KC-IL1β mice, and followed them longitudinally. We used pancreatic 3D in vitro culture to assess acinar-to-ductal metaplasia formation. Immune cells were analysed by flow cytometry and immunohistochemical staining. B lymphocytes were adoptively transferred or depleted in Kras-mutant mice. B-cell infiltration was analysed in human PDAC samples. RESULTS: KC-IL1β mice developed PDAC with liver metastases. IL-1β treatment increased Kras+/G12D pancreatic spheroid formation. CXCL13 expression and B lymphocyte infiltration were increased in KC-IL1β pancreata. Adoptive transfer of B lymphocytes from KC-IL1β mice promoted tumour formation, while depletion of B cells prevented tumour progression in KC-IL1β mice. B cells isolated from KC-IL1β mice had much higher expression of PD-L1, more regulatory B cells, impaired CD8+ T cell activity and promoted tumorigenesis. IL-35 was increased in the KC-IL1β pancreata, and depletion of IL-35 decreased the number of PD-L1+ B cells. Finally, in human PDAC samples, patients with PDAC with higher B-cell infiltration within tumours showed significantly shorter survival. CONCLUSION: We show here that IL-1β promotes tumorigenesis in part by inducing an expansion of immune-suppressive B cells. These findings point to the growing significance of B suppressor cells in pancreatic tumorigenesis.

DOI： 10.1136/gutjnl-2019-319912

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: This study sought to investigate the utility of constant negative pressure for external drainage of the main pancreatic duct in preventing postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. METHODS: Only patients with soft pancreas were included. In the former period (July 2013 to May 2015), gravity dependent drainage was applied (gravity dependent drainage group), and in the latter period (June 2015 to November 2016), constant negative pressure drainage (negative pressure drainage group) was applied to the main pancreatic duct stent. RESULTS: There were 37 patients in the gravity dependent drainage group and 39 patients in the negative pressure drainage group. Clinically relevant POPF occurred in 21 patients (56.8%) in the gravity dependent drainage group and 13 patients (33.3%) in the negative pressure drainage group (p = 0.040). The incidence rate of major complications (Clavien-Dindo grade > III) was significantly lower in the negative pressure drainage group (13.2%) compared to the gravity dependent drainage group (48.7%) (p = 0.001). In-hospital stay was also significantly shorter in the negative pressure drainage group compared to the gravity dependent drainage group (median 25 vs. 33 days, p = 0.024). Multivariate analysis demonstrated that the gravity dependent drainage was one of the independent risk factors for the incidence of POPF (odds ratio, 3.33; p = 0.032). CONCLUSIONS: In patients with soft pancreas, the incidence rate of clinically relevant POPF may be reduced by applying constant negative pressure to the pancreatic duct stent. It also has a potential to reduce overall incidence of major complications and shorten in-hospital stay after pancreatoduodenectomy.

DOI： 10.1016/j.pan.2019.04.002

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

In many solid tumors, parasympathetic input is provided by the vagus nerve, which has been shown to modulate tumor growth. However, whether cholinergic signaling directly regulates progression of pancreatic ductal adenocarcinoma (PDAC) has not been defined. Here, we found that subdiaphragmatic vagotomy in LSL-Kras +/G12D;Pdx1-Cre (KC) mice accelerated PDAC development, whereas treatment with the systemic muscarinic agonist bethanechol restored the normal KC phenotype, thereby suppressing the accelerated tumorigenesis caused by vagotomy. In LSL-Kras +/G12D;LSL-Trp53 +/R172H;Pdx1-Cre mice with established PDAC, bethanechol significantly extended survival. These effects were mediated in part through CHRM1, which inhibited downstream MAPK/EGFR and PI3K/AKT pathways in PDAC cells. Enhanced cholinergic signaling led to a suppression of the cancer stem cell (CSC) compartment, CD11b+ myeloid cells, TNFα levels, and metastatic growth in the liver. Therefore, these data suggest that cholinergic signaling directly and indirectly suppresses growth of PDAC cells, and therapies that stimulate muscarinic receptors may be useful in the treatment of PDAC.Significance: Subdiaphragmatic vagotomy or Chrm1 knockout accelerates pancreatic tumorigenesis, in part via expansion of the CSC compartment. Systemic administration of a muscarinic agonist suppresses tumorigenesis through MAPK and PI3K/AKT signaling, in early stages of tumor growth and in more advanced, metastatic disease. Therefore, CHRM1 may represent a potentially attractive therapeutic target. Cancer Discov; 8(11); 1458-73. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1333.

DOI： 10.1158/2159-8290.CD-18-0046

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed in several types of human cancers, particularly squamous cell carcinomas. We previously reported that CD109-deficient mice exhibit epidermal hyperplasia and chronic skin inflammation. Although we found that CD109 regulates differentiation of keratinocytes in vivo, the function of CD109 in tumorigenesis remains unknown. In this study, we investigated the role of CD109 in skin tumorigenesis using a two-stage carcinogenesis model in CD109-deficient mice with chronic skin inflammation. Immunohistochemical analysis revealed a higher level of TGF-β protein expression in the dermis of CD109-deficient mice than in that of wild-type mice. Additionally, immunofluorescence analysis showed that Smad2 phosphorylation and Nrf2 expression were enhanced in primary keratinocytes from CD109-deficient mice compared with in those from wild-type mice. Although no significant difference was found in conversion rates from papilloma to carcinoma between wild-type and CD109-deficient mice in the carcinogenesis model, we observed fewer and smaller papillomas in CD109-deficient mice than in wild-type mice. Apoptosis and DNA damage marker levels were significantly reduced in CD109-deficient skin compared with in wild-type skin at 24 h after 7, 12-dimethylbenz (α) anthracene treatment. Furthermore, mutation-specific PCR revealed that the mutation frequency of the H-ras gene was less in CD109-deficient skin than in wild-type skin in this model. These results suggest that CD109 deficiency suppresses skin tumorigenesis by enhancing TGF-β/Smad/Nrf2 pathway activity and decreasing the mutation frequency of the H-ras gene.

DOI： 10.18632/oncotarget.12653

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PubMed

Language：Japanese  

Web of Science

Language：English   Publisher：Surgery Today  

Purposes: We performed a conversation analysis of the speech conducted among the surgical team during three-dimensional (3D)-printed liver model navigation for thrice or more repeated hepatectomy (TMRH). Methods: Seventeen patients underwent 3D-printed liver navigation surgery for TMRH. After transcription of the utterances recorded during surgery, the transcribed utterances were coded by the utterer, utterance object, utterance content, sensor, and surgical process during conversation. We then analyzed the utterances and clarified the association between the surgical process and conversation through the intraoperative reference of the 3D-printed liver. Results: In total, 130 conversations including 1648 segments were recorded. Utterance coding showed that the operator/assistant, 3D-printed liver/real liver, fact check (F)/plan check (Pc), visual check/tactile check, and confirmation of planned resection or preservation target (T)/confirmation of planned or ongoing resection line (L) accounted for 791/857, 885/763, 1148/500, 1208/440, and 1304/344 segments, respectively. The utterance’s proportions of assistants, F, F of T on 3D-printed liver, F of T on real liver, and Pc of L on 3D-printed liver were significantly higher during non-expert surgeries than during expert surgeries. Confirming the surgical process with both 3D-printed liver and real liver and performing planning using a 3D-printed liver facilitates the safe implementation of TMRH, regardless of the surgeon’s experience. Conclusions: The present study, using a unique conversation analysis, provided the first evidence for the clinical value of 3D-printed liver for TMRH for anatomical guidance of non-expert surgeons.

DOI： 10.1007/s00595-024-02835-9

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Language：English   Publisher：Surgery Today  

Purposes: The purpose of this study was to compare the financial burden of surgery for retroperitoneal sarcoma (RPS) and gastric cancer (GC). Methods: All patients who underwent surgery for GC or RPS between 2020 and 2021 at Nagoya University Hospital were included. The clinical characteristics, surgical fees per surgeon, and surgical fees per hour were compared between the two groups. Results: The GC and RPS groups included 35 and 63 patients, respectively. In the latter group, 37 patients (59%) underwent tumor resection combined with organ resection; the most common organ was the intestine (n = 23, 37%), followed by the kidney (n = 16, 25%). The mean operative time (248 vs. 417 min, p < 0.001) and intraoperative blood loss (423 vs. 1123 ml, p < 0.001) were significantly greater in the RPS group than in the GC group. The mean surgical fee per surgeon was USD 1667 in the GC group and USD 1022 in the RPS group (p < 0.001) and USD 1388 and USD 777 per hour, respectively (p < 0.001). Conclusions: The financial burden of surgical treatment for RPS is unexpectedly higher than that for GC.

DOI： 10.1007/s00595-024-02831-z

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PubMed

Language：English  

DOI： 10.1097/SLA.0000000000006547

PubMed

Language：English   Publisher：Anticancer Research  

Background/Aim: Recent studies suggest that PD-L1 expression in immune cells, rather than tumor cells, plays a key role in tumor immunity. Trefoil factor family 1 (TFF1) is a secreted protein expressed mainly by the gastrointestinal epithelium and is related to the development of malignant disease. This study investigated the effects of TFF1 on tumor immunity in a xenograft mouse model of colorectal cancer (CRC). Materials and Methods: MC38 cells were implanted in wild-type (WT) and TFF1KO mice, and the tumor microenvironment was investigated using immunohistochemistry. The circulating immune cells were analyzed using flow cytometry. Results: Tumor growth was suppressed in TFF1KO mice. In the tumor microenvironment, CD8- and CD4-positive T cells and CD11c-positive dendritic cells (DCs) were frequently found in TFF1KO mice. When an immune checkpoint inhibitor was administered to these mice, almost half of the tumors in TFF1KO mice showed a complete response. The number of circulating PD-L1/DCs was markedly associated with tumor volume, with TFF1 deletion accelerating this effect and its injection decreasing it. These findings indicate that loss of TFF1 activates tumor immunity via frequent T-cell priming by DCs, and eventually suppresses tumor growth in CRC. In addition, the number of circulating PD-L1/DCs was identified as a predictive marker of checkpoint-inhibiting therapy efficacy. Conclusion: Loss of TFF1 resulted in accelerated immune response to colorectal cancer. Further studies are needed to investigate the precise mechanisms of TFF1 in immunotolerance and develop a novel TFF1-inhibiting immunotherapeutic strategy for CRC.

DOI： 10.21873/anticanres.17200

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PubMed

Language：English   Publisher：Anticancer Research  

Background/Aim: A deep ultraviolet (DUV) light-emitting diode (LED) is a device that can irradiate electromagnetic waves from 250 nm to 350 nm. Tousled-like kinase 1 (TLK1) encodes a nuclear serine/threonine kinase, which is thought to influence the effects of DUV irradiation in cancer. The aim of this study was to clarify the interaction of TLK1 with DUV irradiation-induced DNA damage in cancer cells. Materials and Methods: Pancreatic cancer cell lines were treated with or without DUV. TLK1 expression and phosphorylation in the two groups were examined. Then, these cancer cell lines were treated with thioridazine (THD), DUV or both. Thereafter, cytomorphology and apoptosis were assessed. Several proteins related to DNA damage, were analyzed in cancer cells treated with DUV and THD. Tumors in a subcutaneous xenograft model were treated with THD, DUV, or both for six weeks. Results: DUV irradiation induced the phosphorylation of TLK1 in pancreatic cancer cell lines. Cytomorphology was significantly changed in pancreatic cancer cells treated with DUV and THD. TLK1 inhibition enhanced DUV irradiation-induced apoptosis in cancer cells. Interestingly, CHK1 and pCHK1 expression was suppressed after TLK1 inhibition. In addition, inhibition of MRE11 led to a decrease in the expression of CHK1 and pCHK1, accompanied by a notable increase in apoptosis. In the subcutaneous xenograft models, the tumor volume in the DUV and THD groups was lower than that in the other groups. Conclusion: TLK1 phosphorylation is an important event in DUV irradiation. DUV irradiation combined with TLK1 inhibition has therapeutic potential in pancreatic cancer cells.

DOI： 10.21873/anticanres.17095

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PubMed

Language：English   Publisher：Cancer Medicine  

Background and Aims: Pancreatic cancer is one of the most lethal malignancies, partly due to resistance to conventional chemotherapy. The chemoresistance of malignant tumors is associated with epithelial-mesenchymal transition (EMT) and the stemness of cancer cells. The aim of this study is to investigate the availability and functional mechanisms of trefoil factor family 1 (TFF1), a tumor-suppressive protein in pancreatic carcinogenesis, to treat pancreatic cancer. Methods: To investigate the role of endogenous TFF1 in human and mice, specimens of human pancreatic cancer and genetically engineered mouse model of pancreatic cancer (KPC/TFF1KO; Pdx1-Cre/LSL-KRASG12D/LSL-p53R172H/TFF1−/−) were analyzed by immunohistochemistry (IHC). To explore the efficacy of extracellular administration of TFF1, recombinant and chemically synthesized TFF1 were administered to pancreatic cancer cell lines, a xenograft mouse model and a transgenic mouse model. Results: The deficiency of TFF1 was associated with increased EMT of cancer cells in mouse models of pancreatic cancer, KPC. The expression of TFF1 in cancer cells was associated with better survival rate of the patients who underwent chemotherapy, and loss of TFF1 deteriorated the benefit of gemcitabine in KPC mice. Extracellular administration of TFF1 inhibited gemcitabine-induced EMT, Wnt pathway activation and cancer stemness, eventually increased apoptosis of pancreatic cancer cells in vitro. In vivo, combined treatment of gemcitabine and subcutaneous administration of TFF1 arrested tumor growth in xenograft mouse model and resulted in the better survival of KPC mice by inhibiting EMT and cancer stemness. Conclusion: These results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity.

DOI： 10.1002/cam4.7395

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PubMed

Language：English   Publisher：HPB  

Background: The standard procedure for middle-third cholangiocarcinoma (MCC) is pancreaticoduodenectomy (PD); hepatopancreaticoduodenectomy (HPD) is often performed despite its high risk. There is no clear selection guidance for these procedures. Methods: Patients with MCC who underwent HPD or PD were retrospectively evaluated. The conventional PD was modified (mPD) to transect the bile duct beyond or close to the cranial level of the portal bifurcation. Results: The mPD group (n = 55) was characterized by older age, shorter operation time, less blood loss, and less frequent complications than were observed in the HPD group (n = 34). The median grossly tumor-free margin of the proximal bile duct (GM) was 13 mm vs 20 mm (P = 0.006). Overall survival did not differ significantly between groups (48% vs 53% at 5 years, P = 0.399). Multivariate analysis identified positive surgical margin as a sole independent prognostic factor (hazard ratio, 1.89; P = 0.043), which was statistically associated with GM length. Five-year survival for mPD patients with GM ≥15 mm was significantly better than that for those who had GM <15 mm (69% vs 33%, P = 0.011) and comparable to that of HPD patients (53%, P = 0.450). Conclusion: The mPD may be recommended in patients with MCC, provided that GM ≥15 mm is expected from the preoperative radiological imaging. Otherwise, HPD should be considered.

DOI： 10.1016/j.hpb.2023.12.008

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PubMed

Language：English   Publisher：Surgery (United States)  

Background: Previous studies have suggested the utility of an indocyanine green plasma clearance rate of the future liver remnant (FLR) (ICGK-F) ≥0.05 in hepatobiliary resection to reduce the surgical risk. The present study aimed to verify whether future liver remnant size rather than ICGK-F matters in extended hepatobiliary resection. Methods: Between 2004 and 2021, patients who underwent right hepatic trisectionectomy with bile duct resection were included. The effect of the FLR volume-to-body weight ratio (FLR/BW) and ICGK-F on posthepatectomy liver failure was evaluated along with other parameters. Results: Among 91 study patients, the median ICGK-F, FLR, and FLR/BW were 0.057 (range, 0.027–0.099), 392 mL (145–705), and 0.78% (0.40–1.37), respectively. Posthepatectomy liver failure occurred in 23 patients. The incidence was 10 (40%) in 25 patients with an ICGK-F <0.05 and 12 (18%) in 65 patients with an ICGK-F ≥0.05 (P = .053); 13 (52%) in 25 patients with a FLR/BW <0.65% and 10 (15%) in 66 patients with a FLR/BW ≥0.65% (P = .001). Multivariate analysis showed that a FLR/BW <0.65% (odds ratio, 11.7; P = .005), age ≥65 years (odds ratio, 31.7; P < .001), and blood loss ≥25 mL/kg (odds ratio, 22.1; P = .004) were independent predictors of posthepatectomy liver failure, but ICGK-F <0.05 was not (P = .499). According to the meeting number of 3 factors, posthepatectomy liver failure incidence was 0 of 22 (0%) in patients with 0 factors, 6 of 43 (14%) in patients with 1, and 17 of 26 (65%) in patients with 2 or 3 (P < .001). Conclusion: A FLR/BW ≥0.65% may serve as a volumetric basis to reduce posthepatectomy liver failure after extended hepatobiliary resection.

DOI： 10.1016/j.surg.2023.09.037

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PubMed

Language：English   Publisher：Annals of Surgery  

Objective: To determine the goal of intraoperative blood loss in hepatectomy for perihilar cholangiocarcinoma. Background: Although massive bleeding can negatively affect the postoperative course, the target value of intraoperative bleeding to reduce its adverse impact is unknown. Methods: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were included. Intraoperative blood loss was adjusted for body weight [adjusted blood loss (aBL)], and the overall postoperative complications were evaluated by the comprehensive complication index (CCI). The impact of aBL on CCI was assessed by the restricted cubic spline regression. Results: A total of 425 patients were included. The median aBL was 17.8 (interquartile range, 11.8-26.3) mL/kg, and the CCI was 40.6 (33.7-49.5). Sixty-three (14.8%) patients had an aBL<10 mL/kg, nearly half (45.4%) of the patients were in the range of 10 ≤aBL<20 mL/kg, and 37 (8.7%) patients had an aBL >40 mL/kg. The spline regression analysis showed a nonlinear incremental association between aBL and CCI; CCI remained flat with an aBL under 10 mL/kg; increased significantly with an aBL ranging from 10 to 20 mL/kg; grew gradually with an aBL over 20 mL/kg. These inflection points of 10 and 20 mL/kg were almost consistent with the cutoff values identified by the recursive partitioning technique. After adjusting for other risk factors for the postoperative course, the spline regression identified a similar model. Conclusions: aBL had a nonlinear aggravating effect on CCI after hepatectomy for perihilar cholangiocarcinoma. The primary goal of aBL should be <10 mL/kg to minimize CCI.

DOI： 10.1097/SLA.0000000000005869

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PubMed

Language：English   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Background: The necessity of a specific T classification for extrahepatic intraductal papillary neoplasm of the bile duct (IPNB) type 2, one of the precursors of cholangiocarcinoma (CC), remains unclear. Methods: Patients who underwent resection for extrahepatic biliary tumors were reviewed. Relapse-free survival (RFS) was compared between IPNB type 2 and CC, stratified by T classification. Results: The cohort involved 443 patients with IPNB type 2 (n = 57) and CC (n = 386). In 342 patients with perihilar tumors, 5-year RFS of IPNB type 2 and CC group was 49.8% versus 34.5% (p =.012), respectively. The RFS was 54.6% versus 47.2% (p =.110) for pT1-2 tumors and 28.6% versus 22.7% (p =.436) for pT3-4 tumors, respectively. In 92 patients with distal tumors, 5-year RFS was 47.4% versus 42.1% (p =.678). The RFS was 68.2% versus 49.6% (p =.422) for pT1 tumors and 18.8% versus 38.3% (p =.626) for pT2-3 tumors, respectively. Multivariate analysis identified that poor histologic grade (HR, 2.105; p <.001), microscopic venous invasion (HR, 1.568; p =.002), and nodal metastasis (HR, 1.547; p <.001) were independent prognostic deteriorators, while tumor type (IPNB type 2 vs. CC) was not. Conclusions: Prognostic impact of IPNB type 2 was limited, suggesting unnecessity of a specific T classification for IPNB type 2 with invasive carcinoma.

DOI： 10.1002/jhbp.1269

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: α-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that α-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of α-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated α-bisabolol (CD-BSB) and the signals pathways associated with α-bisabolol for pancreatic cancer. MATERIALS AND METHODS: Human pancreatic cancer cell lines were treated with or without CD-BSB. Cytomorphology and apoptosis were assessed in these treated groups. In addition, several phosphorylated proteins were analyzed to clarify the signal pathway concerning CD-BSB. In subcutaneous xenograft model, tumor volume and Ki-67 expression were evaluated among Control (untreated), CD-BSB, or Gemcitabine (GEM). RESULTS: CD-BSB significantly changed cytomorphology and induced apoptosis in pancreatic cancer cells. CD-BSB suppressed phosphorylation of focal adhesion kinase (FAK). In addition, pFAK 397 was inhibited by CD-BSB in a concentration-dependent manner in cancer cells. In the subcutaneous xenograft models, the tumor volume in the CD-BSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEM-treated groups. CONCLUSION: We clarified the efficiency of CD-BSB in xenograft tumor using intravenous administration. α-Bisabolol suppresses phosphorylation of FAK 397 and impairs cytoskeletal polymerization in a pancreatic cancer cell line. Further investigations are required to reveal the precise mechanisms of the antitumor effects of solubilized α-bisabolol to facilitate its clinical application. Our data indicate that solubilized α-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.

DOI： 10.21873/anticanres.16245

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Deep ultraviolet (DUV) light spans within the 250 nm to 350 nm invisible wavelength range. Although it strongly damages various cells, the efficacy of DUV irradiation on pancreatic cancer cells has never been clarified. The purpose of this study was to reveal the antitumor effects of DUV irradiation on pancreatic cancer cells. MATERIALS AND METHODS: Human pancreatic cancer cell lines were eradicated with DUV or ultraviolet A (UVA) for 5 s. Several angiogenesis-related proteins were studied in cancer cells after DUV irradiation using a protein antibody array. A subcutaneous xenograft model was established by inoculation of pancreatic cancer cells into mice. Tumors in this model were irradiated with DUV or UVA once or twice for two weeks. Tumor volumes in these groups (DUV×1: one irradiation, DUV×2: two irradiations, and untreated) were analyzed one week after the second irradiation. RESULTS: DUV irradiation significantly changed the cytomorphology of pancreatic cancer cells. In addition, DUV irradiation induced apoptosis on pancreatic cancer cells more strongly than UVA irradiation and no irradiation. Interestingly, lower expression of thrombospondin 1 (TSP1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was identified after DUV treatment. The tumor volume in the DUV-treated groups (DUV×1 and DUV×2) was smaller than that in the untreated group. CONCLUSION: Further investigations are required to reveal the precise mechanisms of the antitumor effects of DUV irradiation and to facilitate its clinical application as a new therapy for pancreatic cancer. Overall, DUV irradiation can be potentially used as a therapeutic option of pancreatic malignancy.

DOI： 10.21873/anticanres.16198

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Web of Science

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407213928

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Standardized criteria for drain removal in hepatobiliary resection are lacking. Here, we evaluated the outcomes of delayed removal policy in this extended surgery. METHODS: Patients undergoing hepatectomy with biliary reconstruction between 2012 and 2018 were retrospectively reviewed. The drains were removed on postoperative day (POD) 7 when the drainage fluid was grossly serous, biochemically normal, and negative for bacterial contamination as assessed by Gram staining; additionally, no abnormal fluid collection was confirmed by computed tomography. Clinically relevant abdominal complications (CRACs), including biliary leakage, pancreatic fistula or intra-abdominal abscess, served as the primary outcome measure. RESULTS: Among 374 study patients, surgical drains were removed in 166 (44.3%) patients who met the criteria. Of these patients, 16 (9.6%) patients subsequently required additional drainage due to CRAC. Drains were retained and exchanged in 208 (55.6%) patients who did not meet the criteria. Of these, exchanged drains were soon removed in 34 patients due to no signs of CRAC. The diagnostic ability of the criteria revealed 0.916 sensitivity, 0.815 specificity, and 0.866 accuracy. CONCLUSION: The four findings on POD 7 worked well as criteria for drain removal, and these criteria may be helpful in drain management after hepatobiliary resection.

DOI： 10.1002/jhbp.1194

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PubMed

Language：Japanese   Publisher：(株)アークメディア  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞ポイント ◆局所進行直腸癌に対し,術前CRTへの分子標的薬併用による局所制御・生存率への上乗せ効果は証明されていない.一方,NACやinduction chemotherapyへの分子標的薬併用による局所制御への上乗せ効果の報告は散見される.◆Stage IV・再発大腸癌では,分子標的薬を併用することで奏効率・腫瘍縮小率が上昇し,原発巣・遠隔転移巣ともR0切除やconversion手術のチャンスが増加する.◆"Cure"をめざした術前治療との併用こそが,分子標的薬の真の使いどころかもしれない.

Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞肝外胆管癌は,非治癒因子が存在しない限り根治切除をめざす.肝外胆管癌は肝門部領域胆管癌と遠位胆管癌に分類され,それぞれ尾状葉を伴う肝葉切除・肝外胆管切除術,膵頭十二指腸切除術(pancreaticoduodenectomy:PD)が標準術式となる.肝門部領域胆管癌に対する肝切除術式を決定する際はBismuth分類が有用である.遠位胆管癌のPDの術式は,胃切除範囲や再建法にバリエーションがあり,上腸間膜動脈周囲リンパ節郭清はリンパ節の適正評価に有用である.これら肝外胆管癌の手術適応は癌遺残度の可能性,血管浸潤,リンパ節転移などの腫瘍因子を考慮したうえで決定する.

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Language：Japanese   Publisher：日本消化器病学会-東海支部  

Language：Japanese   Publisher：(株)アークメディア  

Language：English   Publisher：(一社)日本癌治療学会  

Language：English   Publisher：(一社)日本癌治療学会  

Language：Japanese   Publisher：(株)へるす出版  

Language：Japanese   Publisher：Pancreatology  

Objectives Trefoil Factor Family protein 1 (TFF1) is secreted from mucus-producing cells. The relationship between TFF1 expression and clinical outcome in pancreatic ductal adenocarcinoma (PDAC) remains unknown. We aimed to evaluate the prognostic significance of TFF1 expression in PDAC. Methods TFF1 expression was examined on paraffin-embedded sections from 91 patients with resected PDAC using immunohistochemistry. The relationships between TFF1 expression and clinicopathological features were analyzed. Results Among 91 PDAC patients, 71 patients (79.7%) showed TFF1 expression in cancer cells. In a subgroup of 71 patients, TFF1 expression was predominantly observed in the central part of the tumor, whereas TFF1 expression in the invasion front was reduced in 33 patients (46.4%). A significant correlation between preserved TFF1 expression in the invasion front and lymph node metastasis was observed. Univariate survival analysis revealed that preserved TFF1 expression in the invasion front, positive lymphatic invasion, lymph node metastasis and R1 resection was a significant poor prognostic factor in TFF1-positive PDAC patients. Conclusions TFF1 expression is frequently lost or decreased in the invasion front of human PDAC, and preserved TFF1 expression in the invasion front might predict poor survival in patients with PDAC.

DOI： 10.1016/j.pan.2017.07.188

Web of Science

Scopus

PubMed

Language：English   Publisher：(一社)日本癌学会