Publications by authors named "Masafumi Nakamura"

354 Publications

Contribution of pre-existing neoantigen-specific T cells to a durable complete response after tumor-pulsed dendritic cell vaccine plus nivolumab therapy in a patient with metastatic salivary duct carcinoma.

Immunol Invest 2021 Sep 5:1-17. Epub 2021 Sep 5.

Department of Cancer Immunotherapy, Fukuoka General Cancer Clinic, Fukuoka, Japan.

Although immune checkpoint inhibitors (ICIs) have emerged as new therapeutic options for refractory cancer, they are only effective in select patients. Tumor antigen-pulsed dendritic cell (DC) vaccine therapy activates tumor-specific cytotoxic T lymphocytes, making it an important immunotherapeutic strategy. Salivary ductal carcinoma (SDC) carries a poor prognosis, including poor long-term survival after metastasis or recurrence. In this study, we reported a case of refractory metastatic SDC that was treated with a tumor lysate-pulsed DC vaccine followed by a single injection of low-dose nivolumab, and a durable complete response was achieved. We retrospectively analyzed the immunological factors that contributed to these long-lasting clinical effects. First, we performed neoantigen analysis using resected metastatic tumor specimens obtained before treatment. We found that the tumor had 256 non-synonymous mutations and 669 class I high-affinity binding neoantigen peptides. Using synthetic neoantigen peptides and ELISpot analysis, we found that peripheral blood mononuclear leukocytes cryopreserved before treatment contained pre-existing neoantigen-specific T cells, and the cells obtained after treatment exhibited greater reactivity to neoantigens than those obtained before treatment. Our results collectively suggest that the rapid and long-lasting effect of this combination therapy in our patient may have resulted from the presence of pre-existing neoantigen-specific T cells and stimulation and expansion of those cells following tumor lysate-pulsed DC vaccine and ICI therapy.
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http://dx.doi.org/10.1080/08820139.2021.1973491DOI Listing
September 2021

Repositioning of duloxetine to target pancreatic stellate cells.

Oncol Lett 2021 Oct 20;22(4):744. Epub 2021 Aug 20.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Pancreatic cancer cells (PCCs) are surrounded by an abundant stroma, which is produced by pancreatic stellate cells (PSCs). PSCs promote tumor cell proliferation and invasion. The objective of the current study was to identify compounds that suppress PSC activation. Gene expression profiles of cancer-derived fibroblasts and normal fibroblasts were used, and the pathway analysis suggested altered pathways that were chosen for validation. It was found that the 'neuroactive ligand-receptor interaction' pathway from the Kyoto Encyclopedia of Genes and Genomes pathway analysis was one of the altered pathways. Several compounds related with this pathway were chosen, and changes in PSC activity were investigated using fluorescence staining of lipid droplets, reverse transcription-quantitative PCR, western blotting, and invasion and migration assays. Among these candidates, duloxetine, a serotonin-noradrenaline reuptake inhibitor, was found to suppress PSC activation and disrupt tumor-stromal interaction. Thus, duloxetine may be a potential drug for suppressing PSC activation and pancreatic cancer growth.
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http://dx.doi.org/10.3892/ol.2021.13005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387862PMC
October 2021

Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy.

Cell 2021 Sep 12;184(18):4753-4771.e27. Epub 2021 Aug 12.

Division of Translational Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Chemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is characterized by notorious resistance to current therapies attributed to inherent tumor heterogeneity and highly desmoplastic and immunosuppressive tumor microenvironment (TME). Unique proline isomerase Pin1 regulates multiple cancer pathways, but its role in the TME and cancer immunotherapy is unknown. Here, we find that Pin1 is overexpressed both in cancer cells and cancer-associated fibroblasts (CAFs) and correlates with poor survival in PDAC patients. Targeting Pin1 using clinically available drugs induces complete elimination or sustained remissions of aggressive PDAC by synergizing with anti-PD-1 and gemcitabine in diverse model systems. Mechanistically, Pin1 drives the desmoplastic and immunosuppressive TME by acting on CAFs and induces lysosomal degradation of the PD-1 ligand PD-L1 and the gemcitabine transporter ENT1 in cancer cells, besides activating multiple cancer pathways. Thus, Pin1 inhibition simultaneously blocks multiple cancer pathways, disrupts the desmoplastic and immunosuppressive TME, and upregulates PD-L1 and ENT1, rendering PDAC eradicable by immunochemotherapy.
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http://dx.doi.org/10.1016/j.cell.2021.07.020DOI Listing
September 2021

The current status and future directions of robotic pancreatectomy.

Ann Gastroenterol Surg 2021 Jul 4;5(4):467-476. Epub 2021 Mar 4.

Department of Surgery and Oncology Graduate School of Medical Sciences Kyushu University Fukuoka Japan.

Robotic surgery has emerged as an alternative to laparoscopic surgery and it has also been applied to pancreatectomy. With the increase in the number of robotic pancreatectomies, several studies comparing robotic pancreatectomy and conventional open or laparoscopic pancreatectomy have been published. However, the use of robotic pancreatectomy remains controversial. In this review, we aimed to provide a comprehensive overview of the current status of robotic pancreatectomy. Various aspects of robotic pancreatectomy and conventional open or laparoscopic pancreatectomy are compared, including the benefits, limitations, oncological efficacy, learning curves, and costs. Both robotic pancreatoduodenectomy and distal pancreatectomy have favorable or comparable outcomes to conventional procedures, and robotic pancreatectomy has the potential to be an alternative to open or laparoscopic procedures. However, there are still several disadvantages to robotic platforms, such as prolonged operative duration and the high cost of the procedure. These disadvantages will be improved by developing instruments, overcoming the learning curve, and increasing the number of robotic pancreatectomies. In addition, robotic pancreatectomy is still in the introductory period in most centers and should only be used in accordance with strict indications.
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http://dx.doi.org/10.1002/ags3.12446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316739PMC
July 2021

Impact of the Mayo Adhesive Probability Score on Donor and Recipient Outcomes After Living-donor Kidney Transplantation: A Retrospective, Single-center Study of 782 Transplants.

Transplant Direct 2021 Aug 16;7(8):e728. Epub 2021 Jul 16.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: This study was performed to assess the impact of the Mayo Adhesive Probability (MAP) score on donor and recipient outcomes after living-donor kidney transplantation (LDKT).

Methods: We retrospectively analyzed 782 transplants involving LDKT between February 2008 and October 2019 to assess the correlation between the MAP score and outcome after LDKT. We divided the transplants into 2 groups according to the donor MAP score: 0 (MAP) and 1-5 (MAP).

Results: Compared with the MAP group, donors in the MAP group were significantly older, had higher body mass index, and were more likely to be men. The prevalences of hypertension, hyperlipidemia, and diabetes were also higher among donors in the MAP group than among donors in the MAP group. Operative time, estimated blood loss during donor nephrectomy, and percentage of glomerular sclerosis were significantly greater in the MAP group than in the MAP group. Donor and recipient perioperative complications were comparable between the 2 groups; death-censored graft survival rates also did not significantly differ between groups. Although the recipient mean estimated glomerular filtration rate (eGFR) from postoperative d 1 to 7 was significantly higher in the MAP group than in the MAP group ( = 0.007), eGFR reductions within 5 y after transplantation were similar between groups. There were no significant differences between groups in recipient mortality and biopsy-proven acute rejection episodes within 1 y after transplantation. Additionally, multivariate analysis showed that the only factors affecting recipient eGFR at postoperative d 7 were donor age, recipient age, and female sex ( < 0.001, <0.001, and =0.004, respectively).

Conclusions: The MAP score did not influence surgical complications or graft survival; therefore, it should not affect donor selection.
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http://dx.doi.org/10.1097/TXD.0000000000001185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288887PMC
August 2021

Effect of the 2013 ASCO-CAP HER2 Testing Guideline on the Management of IHC/HER2 2+ Invasive Breast Cancer.

Anticancer Res 2021 Aug;41(8):4143-4149

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background/aim: With advances in anti-HER2 treatment and improved prognoses of HER2-positive breast cancer, the American Society of Clinical Oncology and the American Society of Pathologists (ASCO/CAP) have revised the HER2 diagnostic guidelines several times. We examined how to respond clinically to the revisions of the interpretation of the immunohistochemistry (IHC) method.

Patients And Methods: We re-evaluated 254 patients diagnosed as HER2 IHC equivocal, who underwent fluorescence in situ hybridization (FISH) before and after the IHC diagnostic criteria update in 2013.

Results: Twenty of 131 (15.3%) IHC equivocal cases by the ASCO/CAP 2007 guideline were IHC score 3+ and one of 20 (0.76%) was negative for FISH. Five of 123 (4.1%) IHC equivocal cases by the ASCO/CAP 2013 guideline were negative for IHC as per the 2007 guideline and four were positive for FISH.

Conclusion: After revision of the ASCO/CAP 2013 guideline, 3.3% of HER2-negative cases before the revision should have received anti-HER2 treatment.
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http://dx.doi.org/10.21873/anticanres.15217DOI Listing
August 2021

Efficient pre-treatment for pancreatic cancer using chloroquine-loaded nanoparticles targeting pancreatic stellate cells.

Oncol Lett 2021 Aug 1;22(2):633. Epub 2021 Jul 1.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.

Pancreatic stellate cells (PSCs) play a key role in desmoplastic stroma, which is a characteristic of pancreatic ductal adenocarcinoma (PDAC), and they also enhance the malignancy of pancreatic cancer cells. Our previous study reported chloroquine's mitigating effects on PSC activation; however, the drug is known to induce adverse effects in clinical practice. The present study aimed to reduce chloroquine doses and develop a useful pre-treatment that targets PSCs using nanoparticles. Poly lactic-co-glycolic acid (PLGA) nanoparticles were used as carriers and loaded with indocyanine green (Nano-ICG) or chloroquine (Nano-CQ). Tumor accumulation of Nano-ICG was evaluated using an imaging system. The effects of chloroquine, Nano-CQ and/or chemotherapy drug gemcitabine were investigated in an orthotopic xenograft mouse model. Nano-ICG selectively accumulated in pancreatic tumors and persisted therein for over 7 days after administration. Additionally, Nano-ICG accumulated in the peritoneal metastasized regions, but not in the liver, kidney and normal pancreatic tissues. Nano-CQ reduced the density of activated PSCs at lower chloroquine doses and significantly restrained tumor progression in combination with gemcitabine. In conclusion, the PLGA nanosystem successfully delivered the drug to pancreatic tumors. Nano-CQ efficiently reduced PSC activation and may be a promising novel pre-treatment strategy for PDAC.
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http://dx.doi.org/10.3892/ol.2021.12894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258615PMC
August 2021

Neoantigens elicit T cell responses in breast cancer.

Sci Rep 2021 Jun 30;11(1):13590. Epub 2021 Jun 30.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Neoantigens are tumour-specific antigens that arise from non-synonymous mutations in tumour cells. However, their effect on immune responses in the tumour microenvironment remains unclear in breast cancer. We performed whole exome and RNA sequencing of 31 fresh breast cancer tissues and neoantigen prediction from non-synonymous single nucleotide variants (nsSNVs) among exonic mutations. Neoantigen profiles were determined by predictive HLA binding affinity (IC < 500 nM) and mRNA expression with a read count of ≥ 1. We evaluated the association between neoantigen load and expression levels of immune-related genes. Moreover, using primary tumour cells established from pleural fluid of a breast cancer patient with carcinomatous pleurisy, we induced cytotoxic T lymphocytes (CTLs) by coculturing neoantigen peptide-pulsed dendritic cells (DCs) with autologous peripheral lymphocytes. The functions of CTLs were examined by cytotoxicity and IFN-γ ELISpot assays. Neoantigen load ranged from 6 to 440 (mean, 95) and was positively correlated to the total number of nsSNVs. Although no associations between neoantigen load and mRNA expression of T cell markers were observed, the coculture of neoantigen-pulsed DCs and lymphocytes successfully induced CTLs ex vivo. These results suggest that neoantigen analysis may have utility in developing strategies to elicit T cell responses.
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http://dx.doi.org/10.1038/s41598-021-91358-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245657PMC
June 2021

PTPN3 is a potential target for a new cancer immunotherapy that has a dual effect of T cell activation and direct cancer inhibition in lung neuroendocrine tumor.

Transl Oncol 2021 Sep 13;14(9):101152. Epub 2021 Jun 13.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

In our previous study, we found that inhibition of protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is expressed in lymphocytes, enhances lymphocyte activation, suggesting PTPN3 may act as an immune checkpoint molecule. However, PTPN3 is also expressed in various cancers, and the biological significance of PTPN3 in cancer cells is still not well understood, especially for lung neuroendocrine tumor (NET).Therefore, we analyzed the biological significance of PTPN3 in small cell lung cancer and examined the potential for PTPN3 inhibitory treatment as a cancer treatment approach in lung NET including small cell lung cancer (SCLC) and large cell neuroendocrine cancer (LCNEC). Experiments in a mouse xenograft model using allo lymphocytes showed that PTPN3 inhibition in SCLC cells enhanced the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In addition, PTPN3 was associated with increased vascularization, decreased CD8/FOXP3 ratio and cellular immunosuppression in SCLC clinical specimens. Experiments in a mouse xenograft model using autocrine lymphocytes also showed that PTPN3 inhibition in LCNEC cells augmented the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In vitro experiments showed that PTPN3 is involved in the induction of malignant traits such as proliferation, invasion and migration. Signaling from PTPN3 is mediated by MAPK and PI3K signals via tyrosine kinase phosphorylation through CACNA1G calcium channel. Our results show that PTPN3 suppression is associated with lymphocyte activation and cancer suppression in lung NET. These results suggest that PTPN3 suppression could be a new method of cancer treatment and a major step in the development of new cancer immunotherapies.
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http://dx.doi.org/10.1016/j.tranon.2021.101152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208899PMC
September 2021

High frequency of bone recurrence as an initial recurrence site after radical surgery in T1N3 gastric cancer: a propensity score matching analysis.

Langenbecks Arch Surg 2021 Jun 11. Epub 2021 Jun 11.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Purpose: T1 gastric cancer (GC) with seven or more metastatic lymph nodes is extremely rare, and very few clinical studies have been conducted to evaluate the clinicopathological features of their recurrence.

Methods: We retrospectively analyzed the outcomes of T1 GC and T2-4 GC patients who had multiple nodal metastases after radical surgery from 2006 to 2020. Propensity score matching was performed to compare the two groups of patients.

Results: After propensity score matching, 18 of 22 patients in the T1 group and 36 of 144 patients in the T2-4 group were selected. Recurrence occurred in six patients (33.3%) in the T1 group. In the T1 group, the most common site of initial recurrence was bone (15.0%). The prevalence of bone recurrence was significantly higher in the T1 group than in the T2-4 group (P = 0.02). The median interval time between radical surgery and bone recurrence was 24 months, and the median survival time after bone recurrence was 14 months.

Conclusion: Bone recurrence was more frequently identified as an initial recurrence site in T1 GC cases with multiple metastases after radical surgery compared with that in T2-4 GC cases. Careful attention should be paid to postoperative bone recurrence in the long-term postoperative course of these patients.
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http://dx.doi.org/10.1007/s00423-021-02231-8DOI Listing
June 2021

Passive Air Sampling of PCDD/Fs, PCBs, PAEs, DEHA, and PAHs from Informal Electronic Waste Recycling and Allied Sectors in Indian Megacities.

Environ Sci Technol 2021 07 24;55(14):9469-9478. Epub 2021 May 24.

School of Planning and Public Affairs, University of Iowa, Iowa City, Iowa 52242, United States.

Xenobiotic chemical emissions from the informal electronic waste recycling (EW) sector are emerging problem for developing countries, with scale and impacts that are yet to be evaluated. We report an intensive polyurethane foam disk passive air sampling study in four megacities in India to investigate atmospheric organic pollutants along five transects viz., EW, information technology (IT), industrial, residential, and dumpsites. Intraurban emission sources were estimated and attributed by trajectory modeling and positive matrix factorization (PMF). ∑PCDD/Fs, ∑PCBs, ∑plasticizers, and ∑PAHs concentrations ranged from 3.1 to 26 pg/m (14 ± 7; Avg ± SD), 0.5-52 ng/m (9 ± 12); 7.5-520 ng/m, (63 ± 107) and 6-33 ng/m (17 ± 6), respectively. EW contributed 45% of total PCB concentrations in this study and was evidenced as a major factor by PMF. The dominance of dioxin-like PCBs (dl-PCBs), particularly PCB-126, reflects combustion as the possible primary emission source. PCDD/Fs, PCBs and plasticizers were consistently highest at EW transect, while PAHs were maximum in industrial transect followed by EW. Concentrations of marker plasticizers (DnBP and DEHP) released during EW activities were significantly higher ( < 0.05) in Bangalore than in other cities. Toxic equivalents (TEQs) due to dl-PCBs was maximum in the EW transect and PCB-126 was the major contributor. For both youth and adult, the highest estimated inhalation risks for dl-PCBs and plasticizers were seen at the EW transect in Bangalore, followed by Chennai and New Delhi.
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http://dx.doi.org/10.1021/acs.est.1c01460DOI Listing
July 2021

Impact of Recipient Age on Outcomes After Pancreas Transplantation.

Transplant Proc 2021 Jul-Aug;53(6):2046-2051. Epub 2021 May 18.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. Electronic address:

Background: Few reports have provided the ages of pancreas transplant recipients. The aim of this study was to determine whether recipient age affects survival of pancreatic grafts after transplantation.

Methods: We analyzed 73 patients who had undergone pancreas transplantation at our institution from August 2001 to March 2020 and assessed the effects of recipient age on pancreas graft survival within 5 years after pancreas transplantation.

Results: The cutoff value for recipient age established by receiver operating characteristic curve was 35 years. The pancreas graft survival rate of recipients aged 35 years or younger (1, 3, and 5 years: 72.9%, 41.7%, and 41.7%, respectively) was significantly lower than that of recipients aged over 35 years (1, 3, and 5 years: 93.2%, 88.4%, and 88.4%, respectively). Multivariate Cox hazard regression analysis showed that recipient age 35 years or younger (hazard ratio = 3.60; 95% confidence interval, 1.04-12.50; P = .044) and solitary pancreas transplantation (hazard ratio = 10.72; 95% confidence interval, 2.72-42.28; P < .001) were significant risk factors for pancreas graft loss within 5 years.

Conclusion: Our data suggest that younger recipient age is a risk factor for pancreas graft loss after transplantation.
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http://dx.doi.org/10.1016/j.transproceed.2021.04.013DOI Listing
May 2021

Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel Regimen for Borderline Resectable Pancreatic Cancer with Arterial Involvement: A Prospective Multicenter Single-Arm Phase II Study Protocol.

Int J Surg Protoc 2021 Apr 26;25(1):55-60. Epub 2021 Apr 26.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Japan.

Introduction: Although neoadjuvant treatment is recommended for patients with borderline resectable pancreatic cancer (BRPC), no standard neoadjuvant regimen has been established for BRPC with arterial involvement (BRPC-A), which is associated with a higher risk of margin-positive resection and poorer prognosis than BRPC with only venous involvement. Gemcitabine plus nab-paclitaxel (GnP) has been reported to significantly reduce tumor size in metastatic pancreatic cancer, and some retrospective studies suggested that neoadjuvant GnP for BRPC improved resectability and survival.

Methods And Analysis: A prospective multicenter single-arm phase II study is conducted to evaluate the safety and efficacy of GnP as neoadjuvant chemotherapy for BRPC-A. The primary endpoint is the R0 resection rate. The secondary endpoints are the neoadjuvant chemotherapy response rate, resection rate, pathological response rate, incidence rate of adverse events, and quality of life.

Ethics And Dissemination: This study protocol was approved by the institutional review board of Kyushu University (no. 181). The results will be published in a peer-reviewed journal and will be presented at medical meetings.

Highlights: Strategy for borderline resectable pancreatic cancer involving arteries (BRPC-A).There is no standard regimen for neoadjuvant chemotherapy for BRPC-A.Gemcitabine plus nab-paclitaxel (GnP) shows significant tumor shrinkage.Neoadjuvant GnP for BRPC-A increases resectability and margin-negative resection.
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http://dx.doi.org/10.29337/ijsp.142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114838PMC
April 2021

Comparison of outcomes between laparoscopic and open pancreaticoduodenectomy without radical lymphadenectomy: Results of coarsened exact matching analysis using national database systems.

Asian J Endosc Surg 2021 May 16. Epub 2021 May 16.

Japanese Society of Hepato-Biliary-Pancreatic Surgery, Tokyo, Japan.

Introduction: Laparoscopic pancreaticoduodenectomy has recently been covered under Japan's insurance system for patients not requiring lymph node dissection. Only high-volume hospitals that meet specific criteria are permitted to perform laparoscopic pancreaticoduodenectomy. Although open and laparoscopic pancreaticoduodenectomy outcomes with lymph node dissection have been described previously, procedures performed without lymph node dissection have not been compared using a nationwide database. This study aimed to review the results of laparoscopic pancreaticoduodenectomy and compare them to those of open pancreaticoduodenectomy (OPD) using records from a nationwide database.

Methods: We collected patient demographic and medical data of 2900 patients who underwent pancreaticoduodenectomy (laparoscopic, n = 162; open, n = 2738) without lymph node dissection between 2016 and 2018 from the National Clinical Database in Japan. Coarsened exact matching was used to match patients in the laparoscopic and open pancreaticoduodenectomy groups.

Results: In-hospital mortality was not observed in the laparoscopic pancreaticoduodenectomy group. The rate of conversion to an open procedure was 6.8% (11 cases). After 1:1 matching, we obtained 141 pairs of patients for comparison. The mortality rate was comparable in the laparoscopic and open pancreaticoduodenectomy groups (0.0% vs 0.7%, respectively; P = 1.00). The laparoscopic approach showed more favorable results in terms of median blood loss. Postoperative pancreatic fistula formation and complications were comparable between the two groups.

Conclusions: Our results indicate that laparoscopic pancreaticoduodenectomy could be introduced successfully, and the outcomes achieved by the institutions included in our study were comparable to those of open pancreaticoduodenectomy.
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http://dx.doi.org/10.1111/ases.12948DOI Listing
May 2021

Prognostic implications of the coexisting precursor lesion types in invasive gallbladder cancer.

Hum Pathol 2021 Aug 11;114:44-53. Epub 2021 May 11.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. Electronic address:

Invasive gallbladder carcinoma (GBC) is preceded by two main types of precursor lesions: intracholecystic papillary-tubular neoplasms (ICPNs) and biliary intraepithelial neoplasias (BilINs). Invasive GBCs with an ICPN component have more favorable prognoses than those without an ICPN component. Some BilINs show a relatively exophytic papillary pattern but do not meet the ICPN criteria; at our institution, we call these papillary neoplasias. To clarify the clinical significance of papillary neoplasia, we herein examined 80 invasive GBCs and classified them into three groups based on the type of preinvasive lesions: those with ICPN (ICPN group, n = 35), those with papillary neoplasia (pap-neoplasia group, n = 13), and those without ICPN/papillary neoplasia (group without ICPN/pap-neoplasia, n = 32). We then compared the prognostic differences and characterized the tumors of each group by determining the immunohistochemical expressions of various biomarkers. The overall survival periods of the ICPN and pap-neoplasia groups were significantly longer than that of the group without ICPN/pap-neoplasia (P < 0.0001, P = 0.0036, respectively). Multivariate analysis revealed that lacking ICPN/papillary neoplasia was independently associated with poor prognosis (P = 0.0007), as were poor differentiation (P = 0.0395), presence of preoperative symptoms (P = 0.0488), and advanced stage (P = 0.0234). Invasive components of the ICPN and pap-neoplasia groups were characterized by higher expressions of p16 and p53 compared with those of the group without ICPN/pap-neoplasia. The prognoses of the invasive GBCs with either papillary neoplasia or ICPN were thus more favorable than those of the invasive GBCs without ICPN/pap-neoplasia. Invasive GBCs with exophytic papillary preinvasive lesions (ICPN and papillary neoplasia) may be biologically different from those without such lesions.
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http://dx.doi.org/10.1016/j.humpath.2021.05.001DOI Listing
August 2021

New high-throughput screening detects compounds that suppress pancreatic stellate cell activation and attenuate pancreatic cancer growth.

Pancreatology 2021 Apr 20. Epub 2021 Apr 20.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. Electronic address:

Background/objectives: Pancreatic stellate cells (PSCs) are involved in abundant desmoplasia, which promotes cancer cell aggressiveness and resistance to anti-cancer drugs. Therefore, PSCs are suggested to be a promising therapeutic target by attenuating PSC activation to inhibit tumor-stromal interactions with pancreatic cancer cells. Here, we developed a screen to identify compounds that reduce the activity of PSCs and investigated the effect of candidates on pancreatic cancer.

Methods: Lipid droplet accumulation in PSCs was used to observe differences in PSC activity and a new high-throughput screening platform that quantified lipid droplets in PSCs was established. A library of 3398 Food and Drug Administration-approved drugs was screened by this platform. Validation assays were performed in vitro and in vivo.

Results: Thirty-two compounds were finally selected as candidate compounds by screening. These compounds decreased α-smooth muscle actin expression and inhibited autophagic flux in PSCs in vitro. Among the candidates, three drugs selected for validation assays inhibited the proliferation and migration of PSCs and invasion of cancer cells by disrupting tumor-stromal interactions. Production of extracellular matrix molecules was also decreased significantly by this treatment. In vivo testing in xenograft models showed that dopamine antagonist zuclopenthixol suppressed tumor growth; this suppression was significantly increased when combined with gemcitabine.

Conclusions: A new screening platform that focused on the morphological features of PSCs was developed. Candidate drugs from this screening suppressed PSC activation and tumor growth. This screening system may be useful to discover new compounds that attenuate PSC activation.
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http://dx.doi.org/10.1016/j.pan.2021.04.002DOI Listing
April 2021

Bone marrow-derived macrophages converted into cancer-associated fibroblast-like cells promote pancreatic cancer progression.

Cancer Lett 2021 Aug 5;512:15-27. Epub 2021 May 5.

Department of Surgery and Oncology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a desmoplastic reaction caused by cancer-associated fibroblasts (CAFs), which provokes treatment resistance. CAFs are newly proposed to be heterogeneous populations with different functions within the PDAC microenvironment. The most direct sources of CAFs are resident tissue fibroblasts and mesenchymal stem cells, however, the origins and functions of CAF subtypes remain unclear. Here, we established allogeneic bone marrow (BM) transplantation models using spontaneous PDAC mice, and then investigated what subtype cells derived from BM modulate the tumor microenvironment and affect the behavior of pancreatic cancer cells (PCCs). BM-derived multilineage hematopoietic cells were engrafted in recipient pancreas, and accumulated at the invasive front and central lesion of PDAC. We identified BM macrophages-derived CAFs in tumors. BM-derived macrophages treated with PCC-conditioned media expressed CAF markers. BM-derived macrophages led the local invasion of PCCs in vitro and enhanced the tumor invasive growth in vivo. Our data suggest that BM-derived cells are recruited to the pancreas during carcinogenesis and that the specific subpopulation of BM-derived macrophages partially converted into CAF-like cells, acted as leading cells, and facilitated pancreatic cancer progression. The control of the conversion of BM-derived macrophages into CAF-like cells may be a novel therapeutic strategy to suppress tumor growth.
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http://dx.doi.org/10.1016/j.canlet.2021.04.013DOI Listing
August 2021

Predictive factors associated with relapse of stage II/III colon cancer treated with peroral anti-cancer agents in the adjuvant setting.

Mol Clin Oncol 2021 Jun 15;14(6):122. Epub 2021 Apr 15.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Higashi, Fukuoka 812-8582, Japan.

Postoperative adjuvant chemotherapy for patients with stage III colon cancer (CC) is regarded as the standard treatment worldwide for outcome improvement and relapse prevention. Similarly, high-risk stage II CC requires adjuvant chemotherapy because of its high recurrence rate. Previous randomized controlled trials showed that oxaliplatin (OX), in addition to fluorinated pyrimidine-based therapy for patients with stage II/III CC, significantly improves cancer survival but it remains controversial as to which patient groups should receive OX-containing regimens. Among 1,150 consecutive patients who underwent curative resection for stage II/III CC between 2009 and 2016 at two tertiary hospitals, 349 patients treated with only peroral (PO) fluorinated pyrimidine-based chemotherapy and 149 patients who received fluorinated pyrimidine-based chemotherapy with OX as adjuvant chemotherapy were retrospectively reviewed. The primary outcome was recurrence-free survival (RFS). Clinicopathological factors were more advanced in patients treated with OX than in patients treated only with PO fluorinated pyrimidine agents. Multivariate analysis for 5-year RFS showed that T4 [hazard ratio (HR), 2.947; P=0.0001], N2 (HR, 2.704; P=0.0075), vessel or lymphatic invasion (HR, 1.675; P=0.0437) and high cancer antigen (CA)19-9 (HR 3.367, P=0.0002) levels were independent risk factors of cancer relapse. Propensity score matching analysis was performed to match clinicopathological differences between the PO and OX groups. After matching, subgroup analysis of the patients showed that greater effects of OX on cancer survival were observed in patients in the OX group with high CA19-9 levels and tended to be associated with T4 and N2 compared with the PO group. Thus, OX-containing regimens should be recommended for patients with CC with these factors in an adjuvant setting.
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http://dx.doi.org/10.3892/mco.2021.2284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082226PMC
June 2021

Predicting operation time and creating a difficulty scoring system in donor nephrectomy.

J Endourol 2021 Apr 29. Epub 2021 Apr 29.

Kyushu University, 12923, Department of Surgery and Oncology, Graduate School of Medical Sciences, Fukuoka, Japan;

Background: To determine predictive formulas for operation time and surgical difficulty in laparoscopic living-donor kidney transplantation.

Methods: We retrospectively analyzed data for 222 living donors aged > 20 years and recorded factors affecting operation time from patients' computed tomography images and medical records. We used the factors significantly affecting operation time to create a formula to predict operation time and designed a model to predict surgical difficulty based on the standardized partial regression coefficient, β. We also analyzed the relationship between surgical difficulty (high vs low) and operation time.

Results: This study involved 111 pure retroperitoneal donor nephrectomies (PRDN) and 111 hand-assisted laparoscopic donor nephrectomies (HALDN). Patients' mean age was 55.7 years, and 59.5% were women; 5.0% underwent right nephrectomy, and 77.0% vs. 23.0% had single- vs. multiple renal arteries. The average estimated kidney graft weight was 160.0 g; actual average graft weight was 155.3 g. The following factors were significantly correlated with operation time in the regression analysis: number of renal arteries, Mayo adhesive probability (MAP) score, estimated kidney graft weight, right nephrectomy, and operation type (PRDN). These five factors were used to create the operation time prediction equation and difficulty scoring system. The multiple r2 value was 0.40 for the operation time prediction equation. Receiver operating characteristic curve analysis of the difficulty scoring system revealed the following: sensitivity: 78.0%, specificity: 64.9%, and c-statistic: 0.76 (95% confidence interval: 0.70-0.83).

Conclusions: The equation to predict operation time and the surgical difficulty prediction model created in this study are easy to calculate and are accurate. Both may help in selecting an appropriately-skilled surgeon and in improving safety in living-donor kidney transplantation.
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http://dx.doi.org/10.1089/end.2020.1181DOI Listing
April 2021

N-acetyl cysteine induces quiescent-like pancreatic stellate cells from an active state and attenuates cancer-stroma interactions.

J Exp Clin Cancer Res 2021 Apr 15;40(1):133. Epub 2021 Apr 15.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Background: Pancreatic stellate cells (PSCs) occupy the majority of the pancreatic cancer microenvironment, contributing to aggressive behavior of pancreatic cancer cells (PCCs). Recently, anti-fibrotic agents have proven to be an effective strategy against cancer, but clinical trials have shown little efficacy, and the driving mechanism remains unknown. N-acetyl-cysteine (NAC) is often used for pulmonary cystic fibrosis. Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, was habitually used for type II diabetes, but recently reported to inhibit metastasis of PCCs. However, few studies have focused on the effects of these two agents on cancer-stromal interactions.

Method: We evaluated the expression of α-smooth muscle actin (α-SMA) and the number of lipid droplets in PSCs cultured with or without NAC. We also evaluated changes in invasiveness, viability, and oxidative level in PSCs and PCCs after NAC treatment. Using an indirect co-culture system, we investigated changes in viability, invasiveness, and migration of PSCs and PCCs. Combined treatment effects of NAC and Pioglitazone were evaluated in PSCs and PCCs. In vivo, we co-transplanted KPC-derived organoids and PSCs to evaluate the effects of NAC and Pioglitazone's combination therapy on subcutaneous tumor formation and splenic xenografted mouse models.

Results: In vitro, NAC inhibited the viability, invasiveness, and migration of PSCs at a low concentration, but not those of PCCs. NAC treatment significantly reduced oxidative stress level and expression of α-SMA, collagen type I in PSCs, which apparently present a quiescent-like state with a high number of lipid droplets. Co-cultured PSCs and PCCs mutually promoted the viability, invasiveness, and migration of each other. However, these promotion effects were attenuated by NAC treatment. Pioglitazone maintained the NAC-induced quiescent-like state of PSCs, which were reactivated by PCC-supernatant, and enhanced chemosensitivity of PCCs. In vivo, NAC and Pioglitazone's combination suppressed tumor growth and liver metastasis with fewer stromal components and oxidative stress level.

Conclusion: NAC suppressed activated PSCs and attenuated cancer-stromal interactions. NAC induces quiescent-like PSCs that were maintained in this state by pioglitazone treatment.
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http://dx.doi.org/10.1186/s13046-021-01939-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050903PMC
April 2021

Evaluation of contrast and denoising effects related to imaging parameters of compressed sensitivity encoding in contrast-enhanced magnetic resonance imaging.

Radiol Phys Technol 2021 Jun 2;14(2):193-202. Epub 2021 Apr 2.

Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, 920-0942, Japan.

To acquire reference data for setting an appropriate compressed sensitivity encoding (CS) for brain lesion detectability, the effects of contrast and noise on contrast-enhanced magnetic resonance imaging (MRI) were evaluated. Gadobutrol at various concentrations and manganese chloride tetrahydrate were used as a phantom. Various CS factors (0-10) and denoising levels (weak, medium, and strong) were assessed. The contrast amount decreased from CS7 in non-denoised images for 0.5-2 mmol/L solutions but slightly decreased from CS7 with denoising. The noise amount significantly increased with an increasing CS factor. Generally, there was a significant difference in the denoising level and rate across all CS factors in the case of the 2 and 0 mmol/L solutions. When the CS factor was increased without denoising, the integrated noise power spectrum (NPS) increased and decreased in the high-frequency and low-frequency areas, respectively. These data can be used to establish settings based on the degree of denoising.
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http://dx.doi.org/10.1007/s12194-021-00617-3DOI Listing
June 2021

Risk Factors and Optimal Methods for Incisional Hernias After Kidney Transplantation: A Single-Center Experience From Asia.

Transplant Proc 2021 Apr 13;53(3):1048-1054. Epub 2021 Mar 13.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:

Background: For kidney transplant patients, incisional hernia (IH) is a major complication resulting from prolonged pretransplant dialysis, immunosuppressive drugs, and the high prevalence of diabetes. However, there have been relatively few studies of IH after kidney transplantation (KT) in Japan and in the greater Asian population. Additionally, operative methods for IH repair have not been established.

Methods: We retrospectively analyzed 465 consecutive patients who underwent KT at our hospital from April 2013 to March 2019. Patients who underwent incisional hernia repair were included in this study, and the follow-up time was extended to September 2020. We defined severe IH as an IH requiring surgical repair. We examine the risk factors for severe IH among KT patients and also discuss the operative methods of IH repair.

Results: During the study period, 7 patients developed severe IH after KT. The cumulative occurrence rate for severe IH was 1.1% 1 year postoperatively. Multivariate logistic regression analyses showed that age at KT and dialysis duration (hazard ratio = 1.112, P = .016; hazard ratio = 1.106, respectively; P = .038) were independent risk factors for severe IH. We used polypropylene mesh for IH repair in all cases, with onlay repair performed in 5 of 7 cases. There was no recurrence or infection after mesh repair during follow-up.

Conclusions: In this study, age at KT and dialysis duration were independent risk factors for severe IH in the Japanese population. Onlay repair with a polypropylene mesh appeared to be a safe and acceptable operation for IH repair after KT.
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http://dx.doi.org/10.1016/j.transproceed.2021.02.012DOI Listing
April 2021

Evaluation of relationship between splenic artery and pancreatic parenchyma using three-dimensional computed tomography for laparoscopic distal pancreatectomy.

Langenbecks Arch Surg 2021 Mar 15. Epub 2021 Mar 15.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Aim: Isolating the root of the splenic artery (SPA) is a challenging procedure in laparoscopic distal pancreatectomy (LDP). We investigated the usefulness of evaluation of the relationship between the SPA and pancreatic parenchyma using three-dimensional computed tomography (3D-CT).

Methods: In total, 104 patients were evaluated. The relationship between the SPA and pancreatic parenchyma was classified into two types: buried and non-buried. Video clips of 50 patients who underwent LDP requiring isolation of the SPA root were reviewed to determine whether the classification is related to difficulty of LDP.

Results: Of the 50 assessed patients who underwent LDP, the relationship between the SPA and pancreatic parenchyma was the buried type in 30 (60.0%) and non-buried type in 20 (40.0%). The buried type was associated with a significantly longer median operative time than the non-buried type (285.0 vs. 235.5 min, respectively; P < 0.01). The median time required to isolate the SPA in the buried type (25.8 min; range, 4.0-101 min) was significantly longer than that in the non-buried type (7.0 min; range, 1.0-27.0 min) (P < 0.001).

Conclusion: Preoperative 3D-CT around the pancreas is practical for predicting the difficulty of SPA isolation and determining the safety of the procedure.
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http://dx.doi.org/10.1007/s00423-021-02101-3DOI Listing
March 2021

GLI2 but not GLI1/GLI3 plays a central role in the induction of malignant phenotype of gallbladder cancer.

Oncol Rep 2021 03 22;45(3):997-1010. Epub 2021 Jan 22.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812‑8582, Japan.

We previously reported that Hedgehog (Hh) signal was enhanced in gallbladder cancer (GBC) and was involved in the induction of malignant phenotype of GBC. In recent years, therapeutics that target Hh signaling have focused on molecules downstream of smoothened (SMO). The three transcription factors in the Hh signal pathway, glioma‑associated oncogene homolog 1 (GLI1), GLI2, and GLI3, function downstream of SMO, but their biological role in GBC remains unclear. In the present study, the biological significance of GLI1, GLI2, and GLI3 were analyzed with the aim of developing novel treatments for GBC. It was revealed that GLI2, but not GLI1 or GLI3, was involved in the cell cycle‑mediated proliferative capacity in GBC and that GLI2, but not GLI1 or GLI3, was involved in the enhanced invasive capacity through epithelial‑mesenchymal transition. Further analyses revealed that GLI2 may function in mediating gemcitabine sensitivity and that GLI2 was involved in the promotion of fibrosis in a mouse xenograft model. Immunohistochemical staining of 66 surgically resected GBC tissues revealed that GLI2‑high expression patients had fewer numbers of CD3+ and CD8+ tumor‑infiltrating lymphocytes (TILs) and increased programmed cell death ligand 1 (PD‑L1) expression in cancer cells. These results suggest that GLI2, but not GLI1 or GLI3, is involved in proliferation, invasion, fibrosis, PD‑L1 expression, and TILs in GBC and could be a novel therapeutic target. The results of this study provide a significant contribution to the development of a new treatment for refractory GBC, which has few therapeutic options.
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http://dx.doi.org/10.3892/or.2021.7947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860001PMC
March 2021

Management of postoperative pancreatic fistula after pancreatoduodenectomy: Analysis of 600 cases of pancreatoduodenectomy patients over a 10-year period at a single institution.

Surgery 2021 06 19;169(6):1446-1453. Epub 2021 Feb 19.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:

Background: Although postoperative pancreatic fistula (POPF) is a common and critical complication of pancreatoduodenectomy (PD), effective strategies to prevent POPF have not yet been completely developed. Because appropriate management of POPF is important to reduce the mortality rate after PD, in this study we aimed to evaluate our approach for the management of POPF after PD, including the postoperative course.

Methods: This retrospective study included 605 consecutive patients who underwent PD at our hospital between 2010 and 2020. All patients who developed POPF were first managed conservatively, with drainage tubes placed during surgery retained to manage POPF. In cases wherein conservative treatment was unsuccessful, open drainage, followed by continuous negative pressure and continuous irrigation, was used. For open drainage, the surgical wound was opened bluntly (approximate length, 5 cm) under local anesthesia, and the fluid was directly and completely drained.

Results: The prevalence of POPF of grades B and C was 15.4% (n = 93) and 0.33% (n = 2), respectively. Of these patients, 1 required reoperation, 43 recovered with conservative management only, 47 required open drainage, and 4 required image-guided percutaneous drainage. Postoperative hemorrhage with a pseudoaneurysm was identified in 3 (0.66%) patients. The postoperative in-hospital mortality rate was low (n = 1, 0.16%). The rate of successful POPF management was 98.9%.

Conclusion: Based on our high success rate in POPF management, we consider open drainage to be a safe primary management method for POPF.
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http://dx.doi.org/10.1016/j.surg.2021.01.010DOI Listing
June 2021

Long-term effects of laparoscopic lateral pelvic lymph node dissection on urinary retention in rectal cancer.

Surg Endosc 2021 Feb 22. Epub 2021 Feb 22.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Background: The addition of lateral pelvic lymph node dissection (LPLND) in rectal cancer surgery has been reported to increase the incidence of post-operative urinary retention. Here, we assessed the predictive factors and long-term outcomes of urinary retention following laparoscopic LPLND (L-LPLND) with total mesorectal excision (TME) for advanced lower rectal cancer.

Methods: This retrospective single-institutional study reviewed post-operative urinary retention in 71 patients with lower rectal cancer who underwent L-LPLND with TME. Patients with preoperative urinary dysfunction or who underwent unilateral LPLND were excluded. Detailed information regarding patient clinicopathologic characteristics, post-void residual urine volume, and the presence or absence of urinary retention over time was collected from clinical and histopathologic reports and telephone surveys. Urinary retention was defined as residual urine > 100 mL and the need for further treatment.

Results: Post-operative urinary retention was observed in 25/71 patients (35.2%). Multivariate analysis revealed that blood loss ≥ 400 mL [odds ratio (OR) 4.52; 95% confidence interval (CI) 1.24-16.43; p = 0.018] and inferior vesical artery (IVA) resection (OR 8.28; 95% CI 2.46-27.81; p < 0.001) were independently correlated with the incidence of urinary retention. Furthermore, bilateral IVA resection caused urinary retention in more patients than unilateral IVA resection (88.9% vs 47.1%, respectively; p = 0.049). Although urinary retention associated with unilateral IVA resection improved relatively quickly, urinary retention associated with bilateral IVA resection tended to persist over 1 year.

Conclusion: We identified the predictive factors of urinary retention following L-LPLND with TME, including increased blood loss (≥ 400 mL) and IVA resection. Urinary retention associated with unilateral IVA resection improved relatively quickly. L-LPLND with unilateral IVA resection is a feasible and safe procedure to improve oncological curability. However, if oncological curability is guaranteed, bilateral IVA resection should be avoided to prevent irreversible urinary retention.
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http://dx.doi.org/10.1007/s00464-021-08364-7DOI Listing
February 2021

The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer.

Cancer Sci 2021 Apr 5;112(4):1655-1668. Epub 2021 Mar 5.

Department of Surgery, Kyushu University Beppu Hospital, Oita, Japan.

Targeting mutated oncogenes is an effective approach for treating cancer. The 4 main driver genes of pancreatic ductal adenocarcinoma (PDAC) are KRAS, TP53, CDKN2A, and SMAD4, collectively called the "big 4" of PDAC, however they remain challenging therapeutic targets. In this study, ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 (ASAP2), one of the ArfGAP family, was identified as a novel driver gene in PDAC. Clinical analysis with PDAC datasets showed that ASAP2 was overexpressed in PDAC cells based on increased DNA copy numbers, and high ASAP2 expression contributed to a poor prognosis in PDAC. The biological roles of ASAP2 were investigated using ASAP2-knockout PDAC cells generated with CRISPR-Cas9 technology or transfected PDAC cells. In vitro and in vivo analyses showed that ASAP2 promoted tumor growth by facilitating cell cycle progression through phosphorylation of epidermal growth factor receptor (EGFR). A repositioned drug targeting the ASAP2 pathway was identified using a bioinformatics approach. The gene perturbation correlation method showed that niclosamide, an antiparasitic drug, suppressed PDAC growth by inhibition of ASAP2 expression. These data show that ASAP2 is a novel druggable driver gene that activates the EGFR signaling pathway. Furthermore, niclosamide was identified as a repositioned therapeutic agent for PDAC possibly targeting ASAP2.
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http://dx.doi.org/10.1111/cas.14858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019229PMC
April 2021

Efficacy of Distal Pancreatectomy Combined With Modified DuVal Procedure in Patients With a High Risk of Postoperative Pancreatic Fistula.

Am Surg 2021 Feb 10:3134821995088. Epub 2021 Feb 10.

Departments of Surgery and Oncology, Graduate School of Medical Sciences, 12923Kyushu University, Fukuoka, Japan.

Background: The incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) remains high. The present study aimed to clarify the efficacy of our modified DuVal (mDuVal) pancreatojejunostomy following DP in patients with a high risk of POPF.

Methods: The medical records of 346 consecutive patients who underwent DP between 2006 and 2016 were retrospectively reviewed. Perioperative features were compared between 24 patients undergoing mDuVal (mDuVal group) and 322 patients undergoing standard DP (standard DP group).

Results: Preoperative American Society of Anesthesiologists physical status 1 was more frequent in the standard group than in the mDuVal group ( = .02). The start of a solid diet after operation was significantly earlier in the mDuVal group than in the standard DP group ( = .01), while there were no significant differences between the groups for clinically relevant POPF, amylase concentration in the drainage fluid on postoperative day 1 and days 3-5, time to drain removal, additional intervention for POPF, overall complications, or postoperative hospital stay.

Discussion: The mDuVal procedure could be an option for patients with a high risk of POPF to improve the outcomes after DP. Further investigation involving large study populations is necessary to clarify the efficacy of this procedure.
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http://dx.doi.org/10.1177/0003134821995088DOI Listing
February 2021

Impact of the introduction of pure retroperitoneoscopic living-donor nephrectomy on perioperative donor outcomes: A propensity score matching comparison with hand-assisted laparoscopic living-donor nephrectomy.

Asian J Endosc Surg 2021 Feb 9. Epub 2021 Feb 9.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Introduction: We previously reported that the outcomes of pure retroperitoneoscopic donor nephrectomy are superior to those of hand-assisted retroperitoneoscopic donor nephrectomy. Consequently, we introduced pure retroperitoneoscopic donor nephrectomy in our hospital. Here, we compared perioperative outcomes between hand-assisted intra-abdominal laparoscopic donor nephrectomy and pure retroperitoneoscopic donor nephrectomy.

Methods: We retrospectively reviewed data from 315 living-donor kidney transplantation procedures performed between October 2015 and December 2020 (213 involving hand-assisted intra-abdominal laparoscopic donor nephrectomy, October 2015 to June 2019; 102 involving pure retroperitoneoscopic donor nephrectomy, May 2019 to December 2020). After propensity score matching, 90 transplantations were included in each group (n = 180 overall).

Results: Donors in the pure retroperitoneoscopic donor nephrectomy group had longer warm ischemia times (P < .001), lower serum C-reactive protein concentrations and white blood cell counts on postoperative day 1 (P < .001 and P < .001, respectively), and shorter postoperative stays (P < .001) than donors in the hand-assisted intra-abdominal laparoscopic donor nephrectomy group. Five (5.6%) modified Clavien-classifiable complications occurred in the hand-assisted intra-abdominal laparoscopic donor nephrectomy group; no complications occurred in the pure retroperitoneoscopic donor nephrectomy group (P = 0.008). One recipient in the hand-assisted intra-abdominal laparoscopic donor nephrectomy group had donor-related delayed graft function. There were no significant differences between groups in recipient estimated glomerular filtration on postoperative day 7.

Conclusion: The introduction of pure retroperitoneoscopic donor nephrectomy was safe and effective. Moreover, it was less invasive and less harmful for donors, compared with hand-assisted intra-abdominal laparoscopic donor nephrectomy; recipient outcomes were equivalent.
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http://dx.doi.org/10.1111/ases.12922DOI Listing
February 2021

Efficacy of Early Endoscopic Ultrasound-Guided Transluminal Drainage for Postoperative Pancreatic Fistula.

Can J Gastroenterol Hepatol 2021 25;2021:6691705. Epub 2021 Jan 25.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Endoscopic ultrasound-guided transluminal drainage (EUS-TD) is generally performed 4 weeks after disease onset for evacuating pancreatic fluid collections. However, the optimal timing for conducting the procedure in those diagnosed with postoperative pancreatic fistula (POPF) has not been established. We aimed to elucidate the efficacy and safety of early EUS-TD procedures for treating POPF.

Methods: We retrospectively reviewed patients diagnosed with POPF who underwent EUS-TD in the Kyushu University Hospital between 2008 and 2019. Clinical features were comparatively analyzed between the two patient groups who underwent either early (≤15 days postoperatively) or late (>15 days postoperatively) EUS-TD. Factors prolonging hospital stay were also analyzed using Cox proportional hazard models.

Results: Thirty patients (median age, 64.5 years) were enrolled. The most common initial operation was distal pancreatectomy with splenectomy (60.0%). Median size of POPF was 69.5 (range, 38-145) mm, and median time interval between surgery and EUS-TD was 17.5 (range, 3-232) days. Totally, 47% patients underwent early EUS-TD. Rates of technical success, clinical success, and complications were 100%, 97%, and 6.9%, respectively. No recurrence of POPF occurred during a median follow-up period of 14 months. Clinical characteristics and outcomes were comparable between the early and late drainage patient groups, except for the rates of infection and nonencapsulation of POPF, which were significantly higher in the early drainage group. Performing simultaneous internal and external drainage (hazard ratio (HR): 0.31; 95% confidence interval (CI): 0.11-0.93, =0.04) and conducting ≥2 treatment sessions (HR: 0.26; 95% CI: 0.08-0.84, =0.02) were significantly associated with prolonged hospitalization after EUS-TD.

Conclusions: EUS-TD is a safe and effective method for managing POPF, regardless of when it is performed in the postoperative period. Once infected POPF occurs, clinicians should not hesitate to perform EUS-TD even within 15 days of the initial operation.
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http://dx.doi.org/10.1155/2021/6691705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850853PMC
August 2021
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