Language：English   Publishing type：Research paper (scientific journal)   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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Language：English   Publishing type：Research paper (scientific journal)   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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Language：English   Publishing type：Research paper (scientific journal)   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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Language：English   Publishing type：Research paper (scientific journal)   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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Language：English   Publisher：Surgery Today  

Retroperitoneal liposarcoma (RPLS) is a rare but challenging neoplasm, which is frequently associated with iliac vessel invasion. We describe how we used a two-step arterial reconstruction technique to perform en bloc resection of a large RPLS involving the iliac arteries in three patients. A temporal long in situ graft bypass was established using a prosthetic vascular graft during dissection of the tumor. This bypass provided an unobscured surgical field, while maintaining blood flow in the lower limb during the operation. After removal of the tumor and washing out the abdominal cavity, the new prosthetic vascular graft of a suitable length was placed. No graft-related complications, including vascular graft infection or graft occlusion, occurred during the follow-up period. This novel technique appears to provide a safe and effective way to remove large RPLSs involving the retroperitoneal major vessels.

DOI： 10.1007/s00595-023-02684-y

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Language：English   Publishing type：Research paper (scientific journal)   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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Minimally Invasive Therapy and Allied Technologies  

Background: The infraportal type of the right posterior bile duct (infraportal RPBD) is a well-known anatomical variation that increases the potential risk of intraoperative biliary injury. The aim of this study is to clarify the clinical value of fluorescent cholangiography during single-incision laparoscopic cholecystectomy (SILC) for patients with infraportal RPBD. Material and methods: Our procedure for SILC utilized the SILS-Port, and another 5-mm forceps was inserted via an umbilical incision. A laparoscopic fluorescence imaging system developed by Karl Storz Endoskope was utilized for fluorescent cholangiography. Between July 2010 and March 2022, 41 patients with infraportal RPBD underwent SILC. We conducted retrospective reviews of patient data, focusing on the clinical value of fluorescent cholangiography. Results: Thirty-one patients underwent fluorescent cholangiography during SILC, but the remaining ten did not. Only one patient who did not undergo fluorescent cholangiography developed an intraoperative biliary injury. The detectability of infraportal RPBD before and during the dissection of Calot’s triangle was 16.1% and 45.2%, respectively. These visible infraportal RPBDs were characterized as connections to the common bile duct. The confluence pattern of infraportal RPBD significantly influenced its detectability during the dissection of Calot’s triangle (p < 0.001). Conclusions: The application of fluorescent cholangiography can lead to safe SILC, even for patients with infraportal RPBD. Its benefit is emphasized when infraportal RPBD is connected to the common bile duct.

DOI： 10.1080/13645706.2023.2217915

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Language：Japanese   Publishing type：Part of collection (book)   Publisher：南江堂  

DOI： 10.15106/j_geka85_1198

CiNii Research

Authorship：Lead author   Language：Japanese   Publishing type：Part of collection (book)   Publisher：南江堂  

DOI： 10.15106/j_geka85_909

CiNii Research

Language：Japanese   Publishing type：Part of collection (book)   Publisher：金原出版  

DOI： 10.18888/op.0000003349

CiNii Research

Language：Japanese   Publisher：Japan Biliary Association  

<p>A 78-year-old man had undergone magnetic compression anastomosis (Yamanouchi method) against iatrogenic hilar bile stricture after partial hepatectomy (segment 4) for liver metastasis from rectal primary neuroendocrine tumor. He was referred to our clinic with relapse of liver tumor and hilar biliary stricture. An abdominal CT and cholangiography showed a new tumor, 13mm in diameter, located between the segment 4 and 1, atrophy of the right anterior sector, and bilateral biliary dilataton. As definitive surgery for the both problems, he underwent hepatic central bisectionectomy plus caudate lobectomy for liver tumor and biliary bypass for biliary stricture. In the latter, two side-to-side bilio-digestive anastomoses were made on the left lateral inferior duct and the right posterior sectoral duct. The stenotic hilar bile duct, which exhibited extensive fibrosis, were left in situ to avoid major vessel injury.</p>

DOI： 10.11210/tando.37.108

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Background/Purpose: Little is known about the features of T1 pancreatic ductal adenocarcinoma (PDAC) and its definition in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system needs validation. The aims were to analyze the clinicopathologic features of T1 PDAC and investigate the validity of its definition. Method: Data from 1506 patients with confirmed T1 PDAC between 2000 and 2019 were collected and analyzed. The results were validated using 3092 T1 PDAC patients from the Surveillance, Epidemiology, and End Results (SEER) database. Results: The median survival duration of patients was 50 months, and the 5-year survival rate was 45.1%. R0 resection was unachievable in 10.0% of patients, the nodal metastasis rate was 40.0%, and recurrence occurred in 55.2%. The current T1 subcategorization was not feasible for PDAC, tumors with extrapancreatic extension (72.8%) had worse outcomes than those without extrapancreatic extension (median survival 107 vs. 39 months, p <.001). Extrapancreatic extension was an independent prognostic factor whereas the current T1 subcategorization was not. The results of this study were reproducible with data from the SEER database. Conclusion: Despite its small size, T1 PDAC displayed aggressive behavior warranting active local and systemic treatment. The subcategorization by the eighth edition of the AJCC staging system was not adequate for PDAC, and better subcategorization methods need to be explored. In addition, the role of extrapancreatic extension in the staging system should be reconsidered.

DOI： 10.1002/jhbp.1316

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Journal of Clinical Oncology  

Background: Neoadjuvant chemotherapy is a common therapeutic procedure for patients with pancreatic cancer. This study aimed to investigate the association between the total psoas area (TPA) and prognosis in patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer. Study design: This retrospective study included patients who underwent neoadjuvant chemotherapy for pancreatic cancer. TPA was measured at the level of the L3 vertebra using computed tomography. The patients were divided into low-TPA and normal-TPA groups. These dichotomizations were separately performed in patients with resectable and those with borderline resectable pancreatic cancer. Results: In total, 44 patients had resectable pancreatic cancer and 71 patients had borderline resectable pancreatic cancer. Overall survival among patients with resectable pancreatic cancer did not differ between the normal- and low-TPA groups (median, 19.8 vs. 21.8 months, p = 0.447), whereas among patients with borderline resectable pancreatic cancer, the low-TPA group had shorter overall survival than the normal-TPA group (median, 21.8 vs. 32.9 months, p = 0.006). Among patients with borderline resectable pancreatic cancer, the low-TPA group was predictive of poor overall survival (adjusted hazard ratio, 2.57, p = 0.037). Conclusion: Low TPA is a risk factor of poor survival in patients undergoing neoadjuvant chemotherapy for borderline resectable pancreatic cancer. TPA evaluation could potentially suggest the treatment strategy in this disease.

DOI： 10.1007/s10147-023-02321-1

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

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 CDBSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEMtreated groups. Conclusion: We clarified the efficiency of CDBSB 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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Language：Japanese   Publisher：南江堂  

DOI： 10.15106/j_geka85_145

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Purposes: This study sought to define the impact of skeletal muscle mass and quality on postoperative outcomes in patients with perihilar cholangiocarcinoma. Methods: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma were included. The normalized total psoas area (TPA) (psoas muscle index [PMI]) and average Hounsfield units of the TPA (psoas muscle density [PMD]) were measured using preoperative computed tomography images. The cohort was dichotomized using the following indices: sex-specific lowest tertile (low PMI and low PMD) and other (normal PMI and normal PMD). Intraoperative and postoperative outcomes were compared, focusing on PMI and PMD. Results: A total of 456 patients were analyzed. The intraoperative blood loss (IBL) was 21.3 ml/kg in the low PMI group and 17.2 ml/kg in the normal PMI group (P =.008). Patients in the low PMI or PMD group experienced postoperative infectious complications more frequently than those in the other groups. The median survival time was 37.8 months in the low PMI group and 54.2 months in the normal PMI group (P =.027). Conclusions: PMI and PMD were closely associated with IBL and postoperative infectious complications. Additionally, PMI impacted long-term survival. These results suggest an importance of improving muscle mass and quality before surgery.

DOI： 10.1002/jhbp.1220

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

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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Language：English   Publishing type：Research paper (scientific journal)   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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Language：Japanese   Publishing type：Part of collection (book)   Publisher：金原出版  

DOI： 10.18888/op.0000003012

CiNii Research

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

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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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407213704

CiNii Research

Publisher：南江堂  

DOI： 10.15106/j_geka84_670

CiNii Research

Publisher：金原出版  

DOI： 10.18888/op.0000002718

CiNii Research

Language：Japanese   Publisher：The Japanese Society of Gastroenterological Surgery  

DOI： 10.5833/jjgs.2021.0083

CiNii Research

Language：Japanese   Publisher：Japan Biliary Association  

DOI： 10.11210/tando.36.66

CiNii Research

Publisher：南江堂  

DOI： 10.15106/j_geka84_136

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nagoya Journal of Medical Science  

Surgical resection is the mainstay of treatment for retroperitoneal liposarcoma (RPLS). Herein, we describe a case of dedifferentiated RPLS successfully treated with an extended surgical approach with adjuvant chemotherapy. A 61-year-old male was referred to our hospital with a chief complaint of chest tightness. Abdominal computed tomography revealed a large retroperitoneal tumor, 11 cm in diameter, extensively invading the surrounding organs: the celiac axis, the splenic artery, the pancreatic body and tail, the lesser curvature of the stomach and the left adrenal gland. Endoscopic ultrasound-guided fine-needle aspiration biopsy confirmed dedifferentiated liposarcoma, suggesting aggressive tumor biology. We performed total gastrectomy combined with distal pancreatectomy with celiac axis and left adrenal gland resection with a curative intent. The postoperative course was almost uneventful. As the pathological findings indicated a positive margin with a well-differentiated liposarcoma component, we added adjuvant chemotherapy with four cycles of doxorubicin and ifosfamide (AI). Five years after primary surgery, regular follow-up CT demonstrated a pulmonary hilar lymph node enlargement and a tumor at paraesophageal locations. After downsizing chemotherapy with eribulin followed by pazopanib, he underwent partial esophagectomy with dissection of the paraesophageal tumor. The pathological findings indicated recurrence of dedifferentiated liposarcoma with a tumor-free surgical margin. He is currently alive without any evidence of recurrence almost 7 years after the first surgery and 15 months after the second surgery. The long-term survival gained in this patient indicates that extended resections and adjuvant chemotherapy could prolong survival in patients even with RPLS with dedifferentiated tumor histology

DOI： 10.18999/nagjms.84.1.200

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Annals of Surgery  

Objective:To evaluate the efficacy and safety of combined vascular resection (VR) in advanced perihilar cholangiocarcinoma (PHC).Summary of Background Data:Hepatectomy combined with portal vein resection (PVR) and/or hepatic artery resection (HAR) is technically demanding but an option only for tumor eradication against PHC involving the hilar hepatic inflow vessels; however, its efficacy and safety have not been well evaluated.Methods:Patients diagnosed with PHC during 2001-2018 were included. Patients who underwent resection were divided according to combined VR. Patients undergoing VR were subdivided according to type of VR. Postoperative outcomes and OS were compared between patient groups.Results:Among the 1055 consecutive patients, 787 (75%) underwent resection (without VR: N = 484, PVR: N = 157, HAR: N = 146). The incidences of postoperative complications and mortality were 49% (without VR vs with VR, 48% vs 50%; P= 0.715) and 2.1% (without VR vs with VR, 1.2% vs 3.6%; P= 0.040), respectively. The OS of patients who underwent resection with VR (median, 30 months) was shorter than that of those who underwent resection without VR (median, 61 months; P < 0.0001); however, it was longer than that of those who did not undergo resection (median, 10 months; P < 0.0001). OS was not significantly different between those who underwent PVR and those who underwent HAR (median, 29 months vs 34 months; P = 0.517).Conclusion:VR salvages a large number of patients from having locally advanced PHC that is otherwise unresectable and is recommended if the hilar hepatic inflow vessels are reconstructable, providing acceptable surgical outcomes and substantial survival benefits.

DOI： 10.1097/SLA.0000000000004322

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Background: Clinical tumor staging is essential information for making a therapeutic decision in cancer. This study aimed to identify the optimal tumor classification system for predicting resectability and survival probability in perihilar cholangiocarcinoma. Methods: Patients who were treated for perihilar cholangiocarcinoma between 2009 and 2018 were enrolled. Local tumor extension was staged radiologically according to a diameter-based classification system in addition to the AJCC, Blumgart, and Bismuth systems. Survival and resectability were compared between T subgroups, and the discriminability of the four systems was assessed with Harrell’s concordance index (C-index). Results: Among 702 study patients, 559 (80.0%) underwent laparotomy, 489 (70.0%) of whom underwent resection. The resectability significantly decreased for more advanced tumors in all systems (P <.001); the AJCC system had the greatest discriminability for resectability (area under the curve 0.721). Overall survival at 5 years was 69.9% for AJCC cT1, 45.8% for cT2, 31.8% for cT3, and 15.3% for cT4 tumors (cT1 vs cT2; P =.002, cT2 vs cT3; P =.008 and cT3 vs cT4; P <.001). The AJCC system had the largest C-index of 0.627. Conclusions: The AJCC T system was the optimal classification system for predicting resectability and survival in perihilar cholangiocarcinoma.

DOI： 10.1002/jhbp.1066

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407213500

CiNii Research

Language：English  

DOI： 10.1097/SLA.0000000000005248

PubMed

Authorship：Lead author   Language：Japanese   Publishing type：Part of collection (book)   Publisher：Gan to kagaku ryoho. Cancer &amp; chemotherapy  

Scopus

Authorship：Lead author   Language：Japanese   Publishing type：Part of collection (book)  

PubMed

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

Background: Intraductal papillary neoplasm of the bile-duct (IPNB) has recently been further subclassified into “so-called IPNBs” (Type-1) and “narrow-sense papillary cholangiocarcinomas” (Type-2), but their differential diagnosis is challenging. This study aimed to reevaluate Type-1 and Type-2 IPNBs. Methods: Consecutive patients who underwent papillary bile-duct tumor resection were included. Using six pathological features (location, mucin secretion, histological architecture, histological type, presence of a low/intermediate-dysplasia component, and proportion of the invasive component), all papillary tumors were scored. Tumors scoring 5–6 were classified as Type-1, 0–1 as Type-2, and 2–4 as Type-Unclassifiable. Results: The 181 papillary bile-duct tumor patients were divided into three groups, consisting of 12 Type-1, 46 Type-2, and 123 Type-Unclassifiable—gray-zone lesions between Type-1 and Type-2 that constituted the largest proportion of papillary tumors. Type-1 tumors were pathologically the least advanced, while the other types showed gradual advancement. The 5-year survival rate was better for patients with Type-1 tumors than for those with Type-Unclassifiable or Type-2 tumors. Conclusion: The scoring system worked well to delineate a continuous spectrum of pathologic features ranging from Type-1, through Type-Unclassifiable, to Type-2, the latter two being challenging to differentially diagnose. Type-1 is regarded as an early neoplasm of Type-Unclassifiable and Type-2.

DOI： 10.1016/j.hpb.2021.03.004

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Background: The efficacy of adjuvant chemotherapy for biliary cancers remains controversial because of conflicting results from previous phase 3 studies that used different key drugs and enrolled patients with heterogeneous tumor sites and disease stages. Fluoropyrimidine seems more beneficial than gemcitabine (GEM) combination regimens in the adjuvant setting; however, data comparing the survival benefit between GEM- and fluoropyrimidine-based regimens are lacking. Methods: Patients who underwent resection for node-positive perihilar cholangiocarcinoma were included. The patients who underwent adjuvant chemotherapy were divided into the S-1 and GEM groups according to the regimen. The recurrence-free survival (RFS) and the overall survival (OS) were compared between the groups and adjusted with propensity scores generated from 14 potentially confounding clinicopathological factors. Results: In total, 186 patients (Surgery alone, n = 71; S-1, n = 60; GEM, n = 55) were included. The S-1 and GEM completion rates were 75% and 65%, respectively. Among the patients who underwent adjuvant therapy, the RFS was longer in the S-1 group patients than the GEM group patients (median, 24.4 months vs 14.9 months; P =.044) whereas the OS was not significantly different between the groups (median, 48.5 months vs 35.0 months; P =.324). After propensity score adjustment, the differences in RFS and OS between the groups were more evident (HR: 2.696, 95% CI: 1.739-4.180 P <.001; HR: 1.988, 95% CI: 1.221-3.238, P <.001, respectively). Conclusions: Compared with adjuvant GEM monotherapy, adjuvant S-1 monotherapy may improve survival in node-positive perihilar cholangiocarcinoma patients.

DOI： 10.1002/jhbp.1005

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Scopus

PubMed

Language：English  

DOI： 10.1097/SLA.0000000000005162

PubMed

DOI： 10.11477/mf.1407213349

CiNii Research

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

Background: Only a few authors have reported negative results for hepatopancreatoduodenectomy (HPD) with simultaneous resection of the portal vein and hepatic artery in a limited number of patients. The aim of the current study was to outline our experience with this superextended surgery and to discuss its clinical value. Methods: Medical records of consecutive patients who underwent resection of perihilar cholangiocarcinoma between 2007 and 2020 were retrospectively reviewed. Results: During the study interval, 650 patients with perihilar cholangiocarcinoma underwent resection. The superextended surgery was performed in only nine (1.4%) patients. Left or right trisectionectomy was primarily performed. For portal vein reconstruction, external iliac vein graft was required in seven patients. For hepatic artery reconstruction, rotating left gastric artery was often used. The median operative time was 870 minutes and blood loss was 2,598 mL. Postoperatively, pancreatic fistula and liver failure occurred in all patients, followed by intraabdominal abscess (n = 8), and bacteremia (n = 4). One patient died on day 86 due to multiple organ failure. Two patients survived for more than 7 years. Conclusions: HPD with simultaneous resection of the portal vein and hepatic artery is demanding but worth performing as the last option, with careful patient selection in experienced centers.

DOI： 10.1002/jhbp.914

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PubMed

Authorship：Lead author   Publisher：金原出版  

DOI： 10.18888/op.0000002097

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANZ Journal of Surgery  

DOI： 10.1111/ans.16162

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Scopus

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：HPB  

DOI： 10.1016/j.hpb.2020.03.016

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Language：Japanese   Publisher：Japan Biliary Association  

<p>Hepatectomy for biliary tract cancer is well-known as a high-risk surgical procedure potentially yielding a high morbidity and mortality. Preoperative biliary drainage (PBD) has been routinely used in Japan, which totally conflicts to the indication in the West. However, recent studies demonstrated that PBD reduced the incidence of liver failure and mortality after right or more extended hepatectomy. Percutaneous transhepatic biliary drainage (PTBD) increased the incidences of catheter tract seeding and disseminated disease, thereby reducing postsurgical survival. This observation revises a PBD-strategy from percutaneous approach to endoscopic one, particularly in Japan. In addition, because preoperative cholangitis is highly associated with postoperative mortality, PBD should be chosen on the basis of the potential risk of procedure-related cholangitis. The first-line PBD is endoscopic naso-biliary drainage in Japan; endoscopic biliary stent or percutaneous biliary drainage in the overseas. Thus, the strategy of PBD still differ among regions or hospitals due to lack in scientific evidence.</p>

DOI： 10.11210/tando.34.781

CiNii Research

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

DOI： 10.1097/SLA.0000000000004465

PubMed

Publisher：南江堂  

DOI： 10.15106/j_geka82_742

CiNii Research

DOI： 10.11477/mf.1407212912

CiNii Research

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

DOI： 10.1186/s40792-019-0745-z

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PubMed

Language：English  

DOI： 10.1186/s40792-018-0547-8

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：HPB  

DOI： 10.1016/j.hpb.2017.07.002

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Scopus

Authorship：Lead author   Language：English   Publisher：Surgery (United States)  

DOI： 10.1016/j.surg.2016.08.024

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Scopus