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Impact of comorbid renal dysfunction in patients with hepatocellular carcinoma on long-term outcomes after curative resection

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World Journal of Gastrointestinal Surgery 2022年第7期14卷 670-684页

作者： Yuzuru Sakamoto Shingo Shimada toshiya kamiyama Ko Sugiyama Yoh Asahi Akihisa Nagatsu Tatsuya Orimo Tatsuhiko Kakisaka Hirofumi Kamachi Yoichi M Ito Akinobu Taketomi Department of Gastroenterological Surgery Hokkaido University Graduate School of MedicineSapporo 060-8638HokkaidoJapan Data Science Center Promotion UnitInstitute of Health Science Innovation for Medical CareHokkaido University HospitalSapporo 060-8648HokkaidoJapan

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignancies ***,the number of patients with chronic kidney disease(CKD)is on the rise because of the increase in lifestyle-related *** To establish a tailored management strategy for HCC patients,we evaluated the impact of comorbid renal dysfunction(RD),as stratified by using the estimated glomerular filtration rate(EGFR),and assessed the oncologic validity of hepatectomy for HCC patients with *** We enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 at our university *** categorized patients into two(RD,EGFR<60 mL/min/1.73 m^(2);non-RD,EGFR≥60 mL/min/1.73 m^(2))and three groups(severe CKD,EGFR<30 mL/min/1.73 m^(2);mild CKD,30≤EGFR<60 mL/min/1.73 m2;control,EGFR≥60 mL/min/1.73 m^(2))according to renal function as defined by the *** survival(OS)and recurrence-free survival(RFS)were compared among these groups with the log-rank test,and we also analyzed survival by using a propensity score matching(PSM)model to exclude the influence of patient *** mean postoperative observation period was 64.7±53.0 *** The RD patients were significantly older and had lower serum total bilirubin,aspartate aminotransferase,and aspartate aminotransferase levels than the non-RD patients(P<0.0001,P<0.001,P<0.05,and P<0.01,respectively).No patient received maintenance hemodialysis after *** the overall postoperative complication rates were similar between the RD and non-RD patients,the proportions of postoperative bleeding and surgical site infection were significantly higher in the RD patients(5.5%vs 1.8%;P<0.05,3.9%vs 1.8%;P<0.05,respectively),and postoperative bleeding was the highest in the severe CKD group(P<0.05).Regardless of the degree of comorbid RD,OS and RFS were comparable,even after PSM between the RD and non-RD groups to exclude the influence of patient characteristics,liver function,and other causes of dea

关键词： Hepatocellular carcinoma Hepatectomy Renal dysfunction Estimated glomerular filtration rate

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α-fetoprotein,vascular endothelial growth factor receptor-1 and early recurrence of hepatoma

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World Journal of Gastroenterology 2012年第4期18卷 340-348页

作者： toshiya kamiyama Masato Takahashi Kazuaki Nakanishi Hideki Yokoo Hirofumi Kamachi Nozomi Kobayashi Michitaka Ozaki Satoru Todo Department of General Surgery Graduate School of MedicineHokkaido University Department of Transplantation Surgery Graduate School of MedicineHokkaido University Department of Molecular Surgery Graduate School of MedicineHokkaido University

AIM:To investigate whether α-fetoprotein (AFP) and vascular endothelial growth factor receptor (VEGFR)-1 correlate with early recurrence of hepatoma/hepatocel-lular carcinoma (HCC).METHODS:From 2000 to 2005,114 consecutive pa-tients with HCC underwent primary curative *** mean age was 60.7 (8.7) years and 94 patients were *** median follow-up period was 71.2 mo (range:43-100 mo).Immediately prior to commencing laparotomy,5 mL bone marrow was aspirated from thesternum and collected in citrate-coated test *** initial 2 mL of bone marrow aspirate was discarded in each *** mRNA and VEGFR-1 mRNA in the bone marrow and peripheral blood (BM-and PH-AFP mRNA and BM-and PH-VEGFR-1 mRNA,respectively) were measured by real-time quantitative reverse transcription polymerase chain *** normal controls,VEGFR-1 mRNA in the bone marrow and peripheral blood was also measured in 11 living liver *** data were evaluated for any correlation with early recurrence,comparing clinical and pathological ***:The cut-off value of the BM-AFP mRNA and PH-AFP mRNA level in patients with HCC was set at 1.92 × 10-7 and zero,respectively,based on data from the controls.A total of 34 (29.8%) and six (5.4%) patients were positive for BM-AFP mRNA and PH-AFP mRNA,*** BM-VEGFR-1 mRNA levels in all HCC patients were higher than those in the normal con-trols,and this was the case also for *** 25-percentile values for the BM-and PH-VEGFR-1 mRNA in HCC patients were used as the cut-off values for assigning the patients into two groups based on these transcript *** High group for BM-VEG-FR-1 mRNA contained 81 (71.1%) HCC cases and the Low group was assigned 33 (28.9%) *** numbers for PH-VEGFR-1mRNA were 78 (75.0%) and 26 (25.0%),*** recurred in 80 patients;in the remnant liver in 48 cases,in the remnant liver and remote tissue in 20,and in the remote tissue alone in ***-AFP mRNA-positive cases

关键词：血管内皮生长因子受体甲胎蛋白肝癌复发早期 mRNA水平逆转录聚合酶链反应 AFP

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High HbA1c is a risk factor for complications after hepatectomy and influences for hepatocellular carcinoma without HBV and HCV infection

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Hepatobiliary Surgery and Nutrition 2021年第4期10卷 454-463页

作者： Shingo Shimada toshiya kamiyama Tatsuya Orimo Akihisa Nagatsu Hirofumi Kamachi Akinobu Taketomi Department of Gastroenterological Surgery I Hokkaido University Graduate School of MedicineSapporoJapan

Background:Currently,the population with type 2 diabetes mellitus(DM)is increasing ***,the influence of DM or hyperglycemia on the outcome of resected hepatocellular carcinoma(HCC)is ***:We analyzed 756 patients with HCC who underwent *** patients were assigned to an HbA1c≥7.0%(H-A1c;n=100)or HbA1c<7.0%(L-A1c;n=656)group depending on their HbA1c level at *** investigated prognoses,clinicopathological characteristics and surgical outcomes including morbidities of HCC patients with high HbA1c,prognoses according to the treatment for DM were also ***:Among all patients and those with hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,overall survival(OS)and relapse-free survival(RFS)did not differ significantly between the H-A1c and L-A1c *** contrast,the 5-year OS rate of the H-A1c group was 55%and that of the L-A1c group 71%among patients without HBV and HCV(NBNC patients)(P=0.03).Among NBNC patients,the median RFS of the H-A1c group was 13 months,and that of the L-A1c group was 26 months(P=0.02).In addition,metformin use was an independent favorable factor for both OS and *** H-A1c group had significantly higher rates of hyperbilirubinemia,wound infection,and ***:HCC patients with high HbA1c might have poor prognoses for both survival and recurrence in *** HbA1c may also be a risk factor for morbidities after *** use may constitute a good option for NBNC patients with HCC.

关键词： Hepatocellular carcinoma(HCC) HbA1c diabetes mellitus(DM) hepatectomy metformin

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Endoscopic naso-pancreatic drainage for the treatment of pancreatic fistula occurring after LDLT

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World Journal of Gastroenterology 2011年第30期17卷 3560-3564页

作者： Akihisa Nagatsu toshiya kamiyama Satoru Todo Masahiko Taniguchi Tomomi Suzuki Hiroyuki Furukawa Tsuyoshi Shimamura Kenichiro Yamashita Hiroshi Kawakami Daisuke Abo Department of General Surgery Graduate School of MedicineHokkaido UniversityN-15W-7Kita-ku060-8638 SapporoJapan Department of Organ Transplantation and Regeneration Graduate School of MedicineHokkaido UniversityN-15W-7Kitaku060-8638 SapporoJapan Division of Organ Transplantation Graduate School of MedicineHokkaido UniversityN-15W-7Kita-ku060-8638 SapporoJapan Department of Molecular Surgery Graduate School of MedicineHokkaido UniversityN-15W-7Kita-ku060-8638 SapporoJapan Department of Gastroenterology Graduate School of MedicineHokkaido UniversityN-15W-7Kita-ku060-8638 SapporoJapan Department of Radiology Graduate School of MedicineHokkaido UniversityN-15W-7Kita-ku060-8638 SapporoJapan

Pancreatic fistula is a quite rare complication in patients who undergo living donor liver transplantation(LDLT).However,in the cases that show pancreatic fistula,the limited volume of the graft and the resultant inadequate liver function may complicate the management of the *** a result,the pancreatic fistula may result in the death of the *** present 2 cases in whichendoscopic treatment was effective against pancreatic fistulas that developed after *** case 1,a 61-yearold woman underwent LDLT for primary biliary *** of a portal venous thrombus caused by a splenorenal shunt,the patient underwent portal vein reconstruction,and a splenorenal shunt was ligated on postoperative day(POD)*** main pancreatic duct was injured during the manipulation to achieve hemostasis,thereby necessitating open ***,discharge of pancreatic fluid continued even after POD *** naso-pancreatic drainage(ENPD)was performed,and this procedure resulted in a remarkable decrease in drain *** refractory pancreatic fistula healed on day 40 after *** case 2,a 58-year-old man underwent LDLT for cirrhosis caused by the hepatitis C *** the portal vein was exposed during thrombectomy,the pancreatic head was injured,which led to the formation of a pancreatic *** therapy was ineffective;therefore,ENPD was *** pancreatic fistula healed on day 38 after *** findings in these 2 cases show that endoscopic drainage of the main pancreatic duct is a less invasive and effective treatment for pancreatic fistulas that develop after LDLT.

关键词：保守治疗肝移植活体引流内镜生后鼻静脉血栓

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Functional transition:Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

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World Journal of Gastrointestinal Surgery 2021年第2期13卷 153-163页

作者： Yosuke Tsuruga toshiya kamiyama Hirofumi Kamachi Tatsuya Orimo Shingo Shimada Akihisa Nagatsu Yoh Asahi Yuzuru Sakamoto Tatsuhiko Kakisaka Akinobu Taketomi Department of Gastroenterological Surgery I Hokkaido University Graduate School of MedicineSapporo 060-8638Japan

BACKGROUND Preoperative portal vein embolization(PVE)is a widely used strategy to enable major hepatectomy in patients with insufficient liver *** induces hypertrophy of the future liver remnant(FLR)and a shift of the functional reserve to the ***,whether the increase of the FLR volume(FLRV)corresponds to the functional transition after PVE remains *** To investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional(3D)computed tomography(CT)and 99mTc-galactosyl-human serum albumin(99mTc-GSA)singlephoton emission computed tomography(SPECT)fusion *** Thirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I,Hokkaido University Hospital between October 2013 and March 2018 were ***-phase dynamic multidetector CT and 99mTc-GSA SPECT scintigraphy were performed at pre-PVE,and at 1 and 2 wk after PVE;3D 99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis *** FLRV(FFLRV)was defined as the total liver volume×(FLR volume counts/total liver volume counts)on the 3D 99m Tc-GSA SPECT CT-fused *** calculated FFLRV was compared with *** FFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE(P<0.01).The increase in FFLRV and FLRV was 55.1%±41.6%and 26.7%±17.8%(P<0.001),respectively,at 1 wk after PVE,and 64.2%±33.3%and 36.8%±18.9%(P<0.001),respectively,at 2 wk after *** 3 of the 33 patients,FFLRV levels decreased below FLRV at 2 *** of the three patients showed rapidly progressive fatty changes in *** biopsy at 4 wk after PVE showed macroand micro-vesicular steatosis of more than 40%,which improved to 10%.Radical resection was performed at 13 wk after *** patient recovered uneventfully without any symptoms of pos-toperative liver *** The

关键词： Preoperative portal vein embolization Hepatectomy 99mTc-galactosyl-human serum albumin single-photon emission computed tomography Future liver remnant volume Functional transition Fatty liver change

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Outcomes of reduction hepatectomy combined with postoperative multidisciplinary therapy for advanced hepatocellular carcinoma

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World Journal of Gastrointestinal Surgery 2021年第10期13卷 1245-1257页

作者： Yoh Asahi toshiya kamiyama Tatsuhiko Kakisaka Tatsuya Orimo Shingo Shimada Akihisa Nagatsu Takeshi Aiyama Yuzuru Sakamoto Hirofumi Kamachi Akinobu Taketomi Department of Gastroenterological Surgery Ⅰ Hokkaido University Graduate School of MedicineSapporo 060-8638HokkaidoJapan

BACKGROUND The prognosis of advanced hepatocellular carcinoma(HCC)that is not indicated for curative hepatectomy remains poor,despite advances in the treatment of HCC,including the development of tyrosine kinase inhibitors(TKIs).The outcomes of reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy,including those of recently treated cases,should be *** To examine the outcomes of combination treatment with reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative *** Thirty cases of advanced HCC that were not indicated for curative hepatectomy,in which reduction hepatectomy was performed between 2000 and 2018 at the Department of Gastroenterological Surgery I,Hokkaido University Graduate School of Medicine,were divided into postoperative complete remission(POCR)(+)and POCR(-)groups,depending on whether POCR of all evaluable lesions was achieved through postoperative *** cases in the POCR(-)group were subdivided into POCR(-)TKI(+)and POCR(-)TKI(-)groups,depending on whether TKIs were administered *** The 5-year overall survival rate and mean survival time(MST)after reduction hepatectomy were 15.7%and 28.40 mo,respectively,for all cases;37.5%and 56.55 mo,respectively,in the POCR(+)group;and 6.3%and 14.84 mo,respectively,in the POCR(-)group(P=0.0041).Tumor size,major vascular invasion,and the number of tumors in the remnant liver after the reduction hepatectomy were also found to be related to survival *** number of tumors in the remnant liver was the only factor that differed significantly between the POCR(+)and POCR(-)groups,and POCR was achieved significantly more frequently when≤3 tumors remained in the remnant liver(P=0.0025).The MST was 33.52 mo in the POCR(-)TKI(+)group,which was superior to the MST of 10.74 mo seen in the POCR(-)TKI(-)group(P=0.0473).CONCLUS

关键词： Hepatocellular carcinoma Reduction hepatectomy Multidisciplinary therapy Tyrosine kinase inhibitors Postoperative complete remission

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Hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus

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World Journal of Hepatology 2017年第36期9卷 1296-1304页

作者： toshiya kamiyama Tatsuhiko Kakisaka Tatsuya Orimo Kenji Wakayama Department of Gastroenterological SurgeryⅠ Graduate School of MedicineHokkaido UniversitySapporo 060-8638Japan

Despite surgical removal of tumors with portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) patients, early recurrence tends to occur, and overall survival(OS) periods remain extremely short. The role that hepatectomy may play in long-term survival for HCC with PVTT has not been established. The operative mortality of hepatectomy for HCC with PVTT has also not been reviewed. Hence, we reviewed recent literature to assess these parameters. The OS of patients who received hepatectomy in conjunction with multidisciplinary treatment tended to be superior to that of patients who did not. Multidisciplinary treatments included the following: preoperative radiotherapy on PVTT; preoperative transarterial chemoembolization(TACE); subcutaneous administration of interferon-alpha(IFN-α) and intra-arterial infusion of 5-fluorouracil(5-FU) with infusion chemotherapy in the affected hepatic artery; cisplatin, doxorubicin and 5-FU locally administered in the portal vein; and subcutaneous injection of IFN-α, adjuvant chemotherapy(5-FU + Adriamycin) administration via the portal vein with postoperative TACE, percutaneous isolated hepatic perfusion and hepatic artery infusion and/or portal vein chemotherapy. The highest reported rate of operative mortality was 9.3%. In conclusion, hepatectomy for patients affected by HCC with PVTT is safe, has low mortality and might prolong survival in conjunction with multidisciplinary treatment.

关键词： Hepatocellular carcinoma Portal vein tumor thrombus Hepatectomy Multidisciplinary treatment Operative mortality

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Portal vein stenosis after pancreatectomy following neoadjuvant chemoradiation therapy for pancreatic cancer

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World Journal of Gastroenterology 2013年第16期19卷 2569-2573页

作者： Yosuke Tsuruga Hirofumi Kamachi Kenji Wakayama Tatsuhiko Kakisaka Hideki Yokoo toshiya kamiyama Akinobu Taketomi Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine

Extrahepatic portal vein (PV) stenosis has various causes, such as tumor encasement, pancreatitis and as a postsurgical complication. With regard to post-pancreaticoduodenectomy, intraoperative radiation therapy with/ without PV resection is reported to be associated with PV stenosis. However, there has been no report of PV stenosis after pancreatectomy following neoadjuvant chemoradiation therapy (NACRT). Here we report the cases of three patients with PV stenosis after pancreatectomy and PV resection following gemcitabine-based NACRT for pancreatic cancer and their successful treatment with stent placement. We have performed NACRT in 18 patients with borderline resectable pancreatic cancer since 2005. Of the 15 patients who completed NACRT, nine had undergone pancreatectomy. Combined portal resection was performed in eight of the nine patients. We report here three patients with PV stenosis, and thus the ratio of post-operative PV stenosis in patients with PV resection following NACRT is 37.5% in this series. We encountered no case of PV stenosis among 22 patients operated with PV resection for pancreatobiliary cancer without NACRT during the same period. A relationship between PV stenosis and NACRT is suspected, but further investigation is required to determine whether NACRT has relevance to PV stenosis.

关键词： Pancreatic cancer Portal vein stenosis Neoadjuvant chemoradiation therapy Pancreatectomy Expandable metallic stent

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Significance of functional hepatic resection rate calculated using 3D CT/^(99m)Tc-galactosyl human serum albumin singlephoton emission computed tomography fusion imaging

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World Journal of Gastroenterology 2016年第17期22卷 4373-4379页

作者： Yosuke Tsuruga toshiya kamiyama Hirofumi Kamachi Shingo Shimada Kenji Wakayama Tatsuya Orimo Tatsuhiko Kakisaka Hideki Yokoo Akinobu Taketomi Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine

AIM: To evaluate the usefulness of the functional hepatic resection rate(FHRR) calculated using 3D computed tomography(CT)/^(99m)Tc-galactosyl-human serum albumin(GSA) single-photon emission computed tomography(SPECT) fusion imaging for surgical decision making. METHODS: We enrolled 57 patients who underwent bi- or trisectionectomy at our institution between October 2013 and March 2015. Of these, 26 patients presented with hepatocellular carcinoma, 12 with hilar cholangiocarcinoma, six with intrahepatic cholangiocarcinoma, four with liver metastasis, and nine with other diseases. All patients preoperatively underwent three-phase dynamic multidetector CT and ^(99m)Tc-GSA scintigraphy. We compared the parenchymal hepatic resection rate(PHRR) with the FHRR, which was defined as the resection volume counts per total liver volume counts on 3D CT/^(99m)Tc-GSA SPECT fusion ***: In total, 50 patients underwent bisectionectomy and seven underwent *** reconstruction was performed in 15 patients, including hepatopancreatoduodenectomy in two. FHRR and PHRR were 38.6 ± 19.9 and 44.5 ± 16.0, respectively; FHRR was strongly correlated with PHRR. The regression coefficient for FHRR on PHRR was 1.16(P 1000 m L, and/or macroscopic vascular invasion was significantly smaller than that for patients without these factors(0.73 ± 0.19 vs 0.82 ± 0.18, P < 0.05). Postoperative hyperbilirubinemia was observed in six patients. Major morbidities(Clavien-Dindo grade ≥ 3) occurred in 17 patients(29.8%). There was no case of surgeryrelated ***: Our results suggest that FHRR is an important deciding factor for major hepatectomy, because FHRR and PHRR may be discrepant owing to insufficient hepatic inflow and congestion in patients with preoperative therapies, ma

关键词： 99mTc-galactosyl human serum albumin Singlephoton emission computed tomography Hepatectomy Functiona

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Clinical impacts of mesothelin expression in gastrointestinal carcinomas

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World Journal of Gastrointestinal Pathophysiology 2016年第2期7卷 218-222页

作者： Takahiro Einama Futoshi Kawamata Hirofumi Kamachi Hiroshi Nishihara Shigenori Homma Fumihiko Matsuzawa Tatsuzo Mizukami Yuji Konishi Munenori Tahara toshiya kamiyama Okio Hino Akinobu Taketomi Satoru Todo Department of General Surgery Hokkaido University Graduate School of Medicine Department of Translational Pathology Hokkaido University Graduate School of Medicine Department of Pathology and Oncology Juntendo University School of Medicine Research institute of St.Mary’s Hospital Kurume

Mesothelin,C-ERC/mesothelin is a 40-kD a cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura,peritoneum,and ***,mesothelin has been shown to be overexpressed in several human cancers,including virtually all mesothelioma and pancreatic cancer approximately 70% of ovarian cancer and extra bile duc cancer,and 50% of lung adenocarcinomas and gastric *** full-length human mesothelin gene encodes the primary product,a 71-k Da precursor ***71-kD a mesothelin precursor is cleaved into two products40-k Da C-terminal fragment that remains membranebound via glycosylphosphatidylinositol anchor,and a31-kD a N-terminal fragment,megakaryocyte potentiating factor,which is secreted into the *** biologica functions of mesothelin remain largely unknown However,results of recent studies have suggested tha the mesothelin may play a role of cell proliferation and *** pancreatic cancer,mesothelin expression was immunohistochemically observed in all cases,bu absent in normal pancreas and in chronic pancreatitis Furthermore,the expression of mesothelin was correlated with an poorer patient outcome in severa human *** limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer *** present review discusses the expression and function o mesothelin in cancer cells and the utility of mesothelin as a target of cancer therapy.

关键词： Mesothelin Luminal membrane expression Cytoplasmic expression Tumor marker Cancer therapy

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