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この論文では、結腸直腸癌に対する根治手術後の手術部位感染(以下:SSI)発生は再発高危険因子の一つであると報告されており、腹腔鏡下手術はSSI発生減少に有用である可能性が指摘されております。今回はSSI対策とSSI発生と大腸癌術後再発の関係、SSI減少に有用とされる腹腔鏡下手術が予後改善に寄与するのかについて検討した報告です。以下、詳細を御高覧頂ければ幸いです。 |
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結腸直腸癌における手術部位感染と予後の関係と腹腔鏡下手術の優位性についての検討 |
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小池卓也1), 向井正哉1), 木島享子1), 横山大樹1), 宇田周司1), 長谷川小百合1), 田島隆行2), 和泉秀樹1),野村栄治1), 杉山朋子3), 田尻琢磨3)
東海大学医学部付属八王子病院 消化器外科1)
東海大学医学部付属東京病院 外科2)
東海大学医学部付属八王子病院 病理診断科3)
【要旨】
結腸直腸癌に対する根治手術後の手術部位感染(以下:SSI)発生は、再発高危険因子の一つであると報告されている。また、腹腔鏡下手術はSSI発生減少に有用である可能性が指摘されている。今回、自施設のSSI対策を報告するとともに、SSI発生と大腸癌術後再発の関係、SSI減少に有用とされる腹腔鏡下手術が予後改善に寄与する可能性を検討した。2015年1月から2017年12月までに当院で根治手術を受けた大腸癌症例のうち、手術時に遠隔転移を認めないStageⅠ~Ⅲ症例197例を対象に検討した。電子カルテ上で後方視的に症例を分析し、SSIを認めない群(非SSI群)と認めた群(SSI群)の2群に分類し、5
year-relapse free survival (RFS)・5 year-overall survival (OS)を算出し比較検討した。また、非SSI群と創部SSI群、臓器/体腔内SSI群の3群による予後との関係性や、SSI発生率低下に有用とされる腹腔鏡下手術の有用性についても検討した。非SSI群は159例、SSI群は38例に分類された。5Y-RFSは80.5
% vs 63.2 %(P=0.024;ハザード比2.065 [95%信頼区間 1.099-3.883])、5Y-OSは88.7 % vs 84.2
%(P=0.443;ハザード比1.436 [95%信頼区間 0.570-3.617])とSSI群は5YRFSで有意差をもって予後不良であった。腹腔鏡下手術との関係では、SSI発生率は開腹手術
45.0 %(9/20例)、腹腔鏡下手術 16.4 %(29例/177例)と腹腔鏡下手術では優位にSSI発生が減少していた(P=0.005)。SSI発生は結腸直腸癌再発の高危険群であり、腹腔鏡下手術はSSI減少に有用である可能性が示唆された。
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The association between surgical site infection and postoperative colorectal
cancer recurrence and the effect of laparoscopic surgery on prognosis. |
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Abstract. |
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Purpose : Studies have shown that surgical site infection (SSI) incidence
is lower in patients undergoing laparoscopic surgery. Therefore, we reported
the SSI countermeasures adopted by our institution and aimed to evaluate
the association between SSI occurrence and postoperative colorectal cancer
recurrence and the usefulness of laparoscopic surgery for prognosis.
Methods : Among the patients with colorectal cancer who underwent radical
surgery at our hospital between January 2015 and December 2017, 197 with
stage I–III cancer without distant metastases were included. We retrospectively
analyzed patients’ electronic medical records and classified them into
the non-SSI (without SSI, n = 159) and SSI (with SSI, n = 38) groups. We
calculated and compared the 5-year relapse-free survival (RFS) and overall
survival (OS) rates. Additionally, we assessed the relationship between
prognosis in the non-SSI, incisional SSI, and organ/space SSI groups and
the usefulness of laparoscopic surgery.
Results : The 5-year RFS and OS were 80.5% versus 63.2% (P = 0.024; hazard
ratio [HR], 2.065; 95% confidence interval [CI], 1.099–3.883) and 88.7%
versus 84.2% (P = 0.443; HR, 1.436; 95% CI, 0.570–3.617), respectively.
The SSI group had a significantly worse 5-year RFS prognosis. Regarding
the relationship with laparoscopic surgery, the SSI incidence was 45.0%
(9/20 cases) and 16.4% (29/177 cases) with laparotomy and laparoscopic
surgery, respectively, indicating a significantly reduced SSI occurrence
with laparoscopic surgery (P = 0.005).
Conclusion : Patients with SSI were at high risk for colorectal cancer
recurrence, and laparoscopic surgery may be useful for reducing SSI.
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Langenbeck's Archives of Surgery (2024) 409:40 |
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https://link.springer.com/journal/423/volumes-and-issues |
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この論文は切除不能・進行再発大腸癌stage IV症例に対し、当科で行っている統一1次治療(1st line)後の2次化学療法(2nd line)による生存成績と安全性/有効性について検討した報告です。本邦で考案・開発され
2010年に発表されたIRISレジメンは、その後種々の報告がされておりますが、最新の分子標的薬+IRISレジメンに対する単一施設での3年OS/MST等を含めた解析結果です。以下、詳細を御高覧頂ければ幸いです。 |
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進行/再発大腸癌stage IV症例に対する2nd line IRISの有用性; 統一1次治療後の単一施設報告 |
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日上滋雄1)、向井正哉1)、横山大樹1)、宇田周司1)、阿部 凛1)、間室奈々1)、木島享子1)、長谷川小百合1)、田島隆行2)、野村栄治1)、幕内博康1)
1) 東海大学医学部付属八王子病院消化器外科
2) 東海大学医学部付属東京病院外科
【要旨】 2012年10月からstage IV大腸癌の2nd line chemotherapyをEpidermal growth factor receptor (EGFR) inhibitor or Vascular endothelial growth factor (VEGF) inhibitor + IRIS(CPT-11+S-1)に統一/変更した。現在までに計3コース以上施行した原発巣切除後の進行再発症例17例と遠隔転移巣を含む切除不能症例24例;計41例(延べ299コース)を対象として、12ヶ月progression-free survival rate (12M-PFS; median survival time, MST)/12ヶ月overall survival rate (12M-OS; MST), 24M-PFS(MST)/24M-OS (MST); 36M-PFS/36M-OSおよび投与コース数(median)を算出し、objective response rate (ORR)/clinical benefit rate (CBR)とAdverse eventsを検討した。12M-PFS; 31.7% (MST 7.6 M)/12M-OS; 70.6%(MST Not reached)、24M-PFS; 12.3% (MST 7.6 M)/24M-OS; 49.4% (MST 22.1 M), 36M-PFS; 6.2%/36M-OS; 32.1%で、投与コース数は中央値6.0コース(3-20コース)であった。ORRは28.6%/CBRは73.2%で、Adverse eventsは、ほとんどの症例でgrade 1, 2が認められたが保存的に軽快し、grade 3のleukopenia 2 cases (4.9%), neutropenia 5 cases (12.2%)の他, malaise/nausea/perforation等が各1例(2.4%)だけ認められた。以上より、この2nd line modified-IRIS regimenは日本人に安全・確実・有効で、high-quality of life (QOL)/high-quality adjusted life year (QALY)でありlong PFS/long OSと考えられた。
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A single-center retrospective analysis of the efficacy and safety of a
modified regimen of irinotecan plus S-1 (IRIS) with molecular targeting
agents as second-line chemotherapy in Japanese patients with recurrent
or nonresectable colorectal cancer. |
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Abstract. |
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As the second-line chemotherapy for stage IV recurrent or nonresectable
colorectal cancer, our hospital started a modified treatment regimen comprising
of IRIS (irinotecan + tegafur/gimeracil/oteracil [S-1]) plus molecular
targeting agents (MTAs), i.e., an epidermal growth factor receptor (EGFR)
inhibitor such as panitumumab (P-mab) or cetuximab (C-mab) or vascular
endothelial growth factor (VEGF) inhibitor such as bevacizumab (B-mab)
since October 2012. The purpose of this study is to evaluate the efficacy
and safety of this modified regimen. This retrospective study included
41 patients with advanced recurrent colorectal cancer at our hospital whom
at least 3 courses of chemotherapy were conducted from January 2015 to
December 2021. Based on the location of the primary tumor, patients were
classified into two group (right-sided group, proximal to the splenic curve,
and left-sided, distal to the splenic curve). We assessed archived data
on RAS and BRAF status and UGT1A1 polymorphisms and use of the VEGF inhibitor
bevacizumab (B-mab) and the EGFR inhibitors panitumumab (P-mab) and cetuximab
(C-mab). In addition, progression-free survival rate (36M-PFS) and the
overall survival rate (36M-OS) were calculated. Furthermore, the respective
median survival time (MST), the median number of treatment courses; the
objective response rate (ORR) and clinical benefit rate (CBR) and the incidence
of adverse events (AEs) were assessed as well. There were 11 patients (26.8%)
in the right-sided group, and 30 patients (73.2%) in the left-sided group.
There were 19 patients with RAS wild type (46.3%) (1 in the right sided
group and 18 in the left sided group). P-mab was used for 16 of these patients
(84.2%), C-mab for 2 (10.5%), and B-mab for 1 (5.3%); the remaining 22
patients (53.7%). Ten (10 patients) in the right group and 12 patients
in the left group were a mutated type and received B-mab. BRAF testing
was performed in 17 patients (41.5%); as more than 50% of patients (58.5%)
were included before the assay's introduction. 5 patients in the right-sided
group and 12 patients in the left-sided group had wild type. There was
no mutated type. UGT1A1 polymorphism was tested in 16/41 patients: Eight
were wild type (8/41 patients, 19.5%) and 8, mutated type. Regarding the
*6/*28 double heterozygous type, there was only 1 patient in the right-sided
group and the remaining 7 patients were in the left-sided group. The total
number of chemotherapy courses was 299, and the median number, 6.0 (range,
3-20). PFS, OS, and MST were as follows: 36M-PFS(Total / Rt / Lt), 6.2%
/ 0.0% / 8.5% (MST; 7.6 months/ 6.3 months/ 8.9 months); and 36M-OS (Total/
Rt / Lt), 32.1% / 0.0% / 44.0% (MST; 22.1 months / 18.8 months / 28.6 months).
The ORR and CBR were 24.4% and 75.6%, respectively. The majority of AEs
were grades 1 or 2 and were improved with conservative treatment. Grade
3 leukopenia was observed in 2 cases (4.9%), neutropenia in 4 cases (9.8%),
and malaise/nausea/diarrhea/perforation in 1 case each (2.4%). Grade 3
leukopenia (2 patients) and neutropenia (3 patients) were more commonly
observed in the left-sided group. Diarrhea and perforation were also common
in the left-sided group. Conclusions: This second-line modified IRIS regimen
with MTAs is safe and effective and results in good PFS and OS. |
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JOURNAL OF GASTROINTESTINAL ONCOLOGY |
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https://jgo.amegroups.com/article/view/74199 |
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この論文は進行大腸癌stage III/N2症例に対し、当科単一施設で行っている統一した手術/術後補助化学療法による臨床成績を比較検討した報告です。リンパ節転移4個以上の広範な転移巣を有する症例でも、5年無再発で経過する予後良好症例を選別するための解析結果です。以下、詳細を御高覧頂ければ幸いです。
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大腸癌Stage Ⅲ/N2症例における新しい予後指標としての転移リンパ節内の散乱パターンに関する臨床病理学的検討 |
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小池卓也1), 向井正哉1), 平岩信一郎2), 木島享子1), 横山大樹1), 宇田周司1), 長谷川小百合1), 田島隆行3), 野村栄治1),
杉山朋子2), 田尻琢磨2)
東海大学医学部付属八王子病院 消化器外科1)
東海大学医学部付属八王子病院 病理診断科2)
東海大学医学部付属東京病院 外科3)
【要旨】 大腸癌stage III/N2症例の再発高危険群/低危険群を選別するためにリンパ節転移巣の免疫組織化学染色を行い、臨床病理学的に比較検討を行った。2014年12月までの約9年間に根治的治癒切除を施行したstage
III/N2症例計53例/668例(7.9%)を対象とした。リンパ節内の癌細胞の散らばりを形態学的に検討してCircumferential localization
patterns like a cystic mass (CLP) groupとScatter patterns like fireworks
(SPF) groupに分類し、原発巣の組織型(分化度)との関連を含めて5 year-relapse free survival (5Y-RFS)/5
year-overall survival (5Y-OS)を算出し比較検討を行った。CLP群は16例(30.2%)でSPF群は37例(69.8%)であった。5Y-RFSは各々75.0%
vs 37.8% (P=0.021)で、5Y-OSは81.3% vs 48.6% (P=0.033)であった(背景検定; 各群not significant)。原発巣の分化度では高分化腺癌(Well;
14例/26.4%)、中分化(Mod; 37例)~低分化腺癌(Por 1; 2例)を含めた(Mod+Por group)が39例(73.6%)であった。これらをWell/CLP
(6 cases)、Well/SPF (8 cases)、Mod+Por/CLP (10 cases)、Mod+Por/SPF (29 cases)の4
groupsに細分類され、5Y-RFSは各々66.7% / 25.0% (P=0.293)、80.0% / 41.4% (P=0.052)で、5Y-OSは66.7%
/ 50.0% (P=0.552)、90.0% / 48.3% (P=0.059)であった。以上より、CLP群は比較的予後良好な再発低危険群と考えられたが、SPF群は再発高危険群として予後不良で、術後早期から分子標的薬等を含むより強力なmulti-combination
chemo.を施行する必要性が示唆された。
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Scatter patterns in lymph node metastases as a novel prognostic indicator
in patients with stage III/N2 colorectal cancer |
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Abstract. |
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To classify patients with stage III/N2 colorectal cancer into high- and
low-risk groups for recurrence, we compared clinicopathological features
by immunohistochemical staining. The single-center analysis included 53/668
patients (7.9%) with stage III/N2 colorectal cancer who underwent radical
resection during the approximately 9 years until December 2014. We examined
cancer cell distribution in metastatic lymph nodes and classified patients
into a group with circumferential localization patterns like a cystic mass
(CLP) and a group with scatter patterns like fireworks (SPF). Then, we
compared 5-year relapse-free survival (5Y-RFS) and 5-year overall survival
(5Y-OS) rates and included the histological type (differentiation degree)
of the primary adenocarcinoma. The CLP group included 16 patients (30.2%)
and the SPF group included 37 (69.8%). The 5Y-RFS rates in these groups
were 75.0% vs 37.8%, respectively (P = 0.021); and the 5Y-OS rates, 81.3%
vs 48.6% (P = 0.033). Patient clinicopathological characteristics showed
no significant differences between groups. The adenocarcinoma was well
differentiated in 14 patients (Well; 26.4%) and moderately (Mod; n=37)
or poorly (Por; n=2) differentiated in 39 (Mod+Por; 73.6%). Patients were
further classified into 4 groups: Well/CLP (n=6), Well/SPF (n=8), Mod+Por/CLP
(n=10), and Mod+Por/SPF (n=29). In Well/CLP vs Well/SPF, 5Y-RFS rates were
66.7% vs 25.0%, respectively (P = 0.293); and in Mod+Por/CLP vs Mod+Por/SPF,
80.0% vs 41.4% (P = 0.052); the respective values for 5Y-OS were 66.7%
vs 50.0% (P = 0.552) and 90.0% vs 48.3% (P = 0.059). Based on the above,
the CLP group was considered a low-risk group for recurrence with a relatively
good prognosis; however, the SPF group was considered a high-risk group
for recurrence with a poor prognosis, suggesting a need for more potent
multi-combination chemotherapy in these patients from the early postoperative
period.
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MOLECULAR and CLINICAL ONCOLOGY |
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Published online on: September 21, 2021 |
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https://doi.org/10.3892/mco.2021.2402
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この論文は進行大腸癌stage IV症例に対し、当科単一施設で行っている統一した1st line化学療法レジメンによる臨床成績を比較検討した報告です。原発巣切除後の進行再発症例27例と来院時遠隔転移巣を含む切除不能症例43例の計70例(施行した化学療法延べ920コース)を対象とし、主として生存成績/有効性や副作用/安全性等についての解析結果です(追跡率74.3%)。以下、詳細を御高覧いただければ幸いです。
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切除不能/進行再発大腸癌Stage IV症例に対するmodified B-mab XELOXの有用性 |
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横山大樹1), 向井正哉1), 宇田周二1), 木島享子1), 小池卓也1), 長谷川小百合1), 和泉秀樹1),
山本壮一郎1), 田島隆行2), 野村栄治1), 幕内博康1).
東海大学医学部付属八王子病院消化器外科1)
東海大学医学部付属東京病院外科2)
【要旨】 2014年4月からstage IV大腸癌の化学療法をB-mab XELOXに統一/変更し、現在までに計3コース以上施行した原発巣切除後の進行再発症例27例と遠隔転移巣を含む切除不能症例43例;計70例(延べ920コース)を対象として、1年無増悪生存期間
(1Y-PFS)/1年全生存期間 (1Y-OS); 3Y-PFS/3Y-OSおよび投与コース数を算出し、objective response
rate/clinical benefit rateとadverse effectを検討した。また、Conversion surgery (CS)-R0手術を施行した症例の術前投与コース数、生存期間、Conversion
R0率を算出した。1Y-PFS; 28.5%(MST 7.4M)/1Y-OS; 76.6%(MST Not reached)、3Y-PFS;
5.5%(MST 7.4M)/3Y-OS; 26.4%(MST 25.2M)で、投与コース数は平均値13.1コース/中央値10.5コースであった。objective
response rate28.6%, clinical benefit rate58.6%で、adverse effectは、grade 1,
2が計60例/70例 (85.7%)に認められたが保存的に軽快し、grade 4の原発巣perforationを1例/70例(1.4%)だけ認めた。Conversion率は7例(10.0%;
原発+肝2例/原発+肺1例/肝3例/原発1例)で、術前の投与コース数は3-10コース; 平均7.3コース/中央値6.5コース、CS-R0率は5/7例
(71.4%)で、術後生存期間は1-26ヵ月(MST8ヵ月)であった。現状は症例集積中でconversion率は低いが、このmodified
regimenは日本人に対して安全・確実・有効で、high QOL/QALYでlong PFS/OSと考えられた。
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Efficacy of modified bevacizumab-XELOX therapy in Japanese patients with
stage IV recurrent or non-resectable colorectal cancer. |
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Abstract. |
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At our hospital, bevacizumab with capecitabine and oxaliplatin (B-mab XELOX)
has been used as 1st line chemotherapy for Stage IV colorectal cancer since
2014. We treated 70 patients received at least 3 cycles of B-mab XELOX
(total: 920 cycles), and also determined the 1-year progression-free survival
(1Y-PFS), 1-year overall survival (1Y-OS), 3Y-PFS, 3Y-OS, and number of
treatment cycles. The objective response rate, clinical benefit rate, and
adverse events were also assessed. Moreover, the number of chemotherapy
cycles, survival time, and R0 surgery rate were determined for patients
who underwent RO conversion surgery. The 1Y-PFS was 28.5% (median survival
time [MST]: 7.4 months), 1Y-OS was 76.6% (MST not reached), 3Y-PFS was
5.5% (MST: 7.4 months), and 3Y-OS was 26.4% (MST: 25.2 months). The mean
and median number of cycles of B-mab XELOX was 13.1 and 10.5, respectively,
while the objective response rate was 28.6% and the clinical benefit rate
was 58.6%. Grade 1 or Grade 2 adverse events were observed in 60 patients
(85.7%), but all of these events resolved without intervention. RO conversion
surgery was performed in 7 patients (10.0%). These patients received from
3 to 10 cycles preoperatively (mean: 7.3; median: 6.5) and R0 surgery was
achieved in 5/7 patients (71.4%). Postoperative survival ranged from 1
to 26 months (MST: 8 months). This modified regimen was safe and effective
in Japanese patients and high quality of life/quality-adjusted life-year
was achieved. To further evaluate PFS and OS, more patients are being investigated.
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JOURNAL OF GASTROINTESTINAL ONCOLOGY |
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https://jgo.amegroups.com/article/view/50687 |
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この論文は進行下部直腸癌に対し、当科単一施設での臨床成績を比較検討した報告です。過去10年間に経験したstage II/III下部直腸癌123例を抜粋し、主として再発様式と生存成績について5年間追跡した解析結果です(追跡率94.3%)。以下、詳細を御高覧頂ければ幸いです。
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Stage II/III下部直腸癌に対する初回骨盤内局所再発と予後に関する臨床病理学的検討 |
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宇田周二1), 向井正哉1), 木島享子1), 横山大樹1), 長谷川小百合1), 小池卓也1), 田島隆行2), 野村栄治1), 富田康介3),
松本知博3), 長谷部光泉3) 幕内博康1)
東海大学医学部付属八王子病院消化器外科(*1)
東海大学医学部付属東京病院外科(*2)
東海大学医学部付属八王子病院画像診断科(*3)
【要旨】進行直腸癌(ARC)に対する再発様式と生命予後に関する比較検討を行った。過去10年間で肉眼的癌遺残の無い根治治癒切除術(TME/TSME;
R0)に術後全身化学療法を施行したclinical-stage II/IIIで, location/RS及びT4+CRT/側方郭清症例を除く全123症例において,
5年無再発生存率(5Y-RFS)と5年全生存率(5Y-OS)を算出した. さらに術後早期合併症, 再発様式と生命予後を比較検討し, これら再発群の5Y-OSを算出した.
5Y-RFSは71.4%, 5Y-OSは83.5%で, 全再発率は28/123例(22.8%)であった. これらの再発様式では遠隔転移が17/123例(13.8%)で,
各々肺8例(6.5%), 肝5例(4.1 %), others 4例(3.3%)であった. 第1再発が骨盤内局所再発(PLR)率は11/123例
(8.9%)で, 各々正中仙骨前面7例(5.7%), 吻合部2例(1.6%), 骨盤内側方2例(1.6%)であった. これら再発群の5Y-OSは各々遠隔転移群69.3%,
骨盤内局所再発群27.3%で, 2群間に有意差が認められた(p=0.02; 背景検定N.S). 以上の結果より, ARC/骨盤内局所制御は治癒切除R0+術後化療で可能と考えられたが,
初回再発がPLRでは肺/肝等全身へのNew metastatic cascadeとなり生命予後に深く関与するものと考えられた.
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Pelvic local recurrence as first relapse predicts prognosis for clinical
stage II/III lower rectal cancer: A clinicopathological investigation. |
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Abstract. |
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We investigated the correlation between the mode of tumor recurrence and
prognosis in 123 patients with clinical stage II/III rectal cancer. In
the past 10 years, patients had received systemic chemotherapy following
radical (R0, with no macroscopic residual tumor lesions) resection using
total or tumor-specific mesorectal excision. Patients with rectosigmoid
cancers and T4 + chemoradiation therapy were excluded. We calculated 5-year
relapse-free survival rate (5Y-RFS), 5-year overall survival rate (5Y-OS),
and correlations between early post-operative complications, recurrence
mode and prognosis, as well as 5Y-OS for patients with relapsed cancer.
Overall 5Y-RFS and 5Y-OS were 71.4% and 83.5%, respectively, and overall
recurrence rate was 28/123 patients (22.8%). Among relapses, remote metastases
were observed in 17/123 patients (13.8%): the lung in 8 patients (6.5%),
the liver in 5 patients (4.1%), and elsewhere in 4 patients (3.3%). Eleven
patients (8.9%) had pelvic local recurrence as the first relapse, located
anterior to the sacrum in seven patients (5.7%), at the anastomosis site
in two patients (1.6%), and in the inner pelvis in two patients (1.6%).
Among relapsed patients, 5Y-OS was 69.3% in those with distant metastases
and 27.3% in those with local relapse (p = 0.02; no significant differences
in patient demographics). The results indicate that advanced rectal cancer
and control of pelvic local recurrence are manageable by R0 resection and
postoperative chemotherapy. However, for patients whose initial relapse
is pelvic local recurrence, the relapsed tumor initiated a new metastatic
cascade to organs such as the lung and liver, and significantly affected
prognosis.
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MOLECULAR and CLINICAL ONCOLOGY Published online on: December 18, 2020 |
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https://doi.org/10.3892/mco.2020.2195 |
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I、II期非小細胞肺癌における郭清リンパ節類洞内遊離癌細胞の
発現と再発/予後に関する検討 (Fast Red染色法を用いた検討) |
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中村雄介(*1)、向井正哉(*2)、平岩真一郎(*3)、木島享子(*2)、杉山朋子(*3)、田尻琢磨(*3)、
山田俊介(*1)、岩崎正之(*4)
東海大学医学部付属八王子病院呼吸器外科(*1)
東海大学医学部付属八王子病院消化器外科(*2)
東海大学医学部付属八王子病院病理診断科(*3)
東海大学医学部外科学系呼吸器外科学(*4)
【要旨】リンパ節の類洞内における遊離癌細胞の発現が、大腸癌、胃癌の予後と深くかかわっていることが多数報告されている。本研究では、根治術を受けた病理病期I/II期非小細胞肺癌および肺門リンパ節転移陽性非小細胞肺癌においても、遊離癌細胞の発現が、再発、予後と深くかかわっているか、その臨床的意義を調査した。遊離癌細胞の検出に用いる、サイトケラチン免疫染色には、Fast
Red染色法を用いた。2002年から2011年に根治術を受けた全164例(22例が肺門リンパ節転移陽性)を調査した。郭清リンパ節に抗サイトケラチン抗体を用いて免疫染色した。炭粉との区別をつきやすくするために、二次抗体にはFast
Red染色法を用いた。この染色法は、抗体に結合したアルカリフォスファターゼが、基質のFast Redとナフトールを反応させ、赤色を呈するようになる染色法である。郭清リンパ節の類洞内にヘマトキシリン、エオジン染色(HE染色)で検出できず、Fast
Red染色法で検出できる遊離癌細胞が1個でも認められたら、その症例は、遊離癌細胞陽性と定義した。全164例中、遊離癌細胞陽性群と陰性群の5年無再発生存率、5年全生存率を比較したところ、遊離癌細胞陽性群の5年無再発生存率は33.3%、陰性群は76.9%と有意に遊離癌細胞陽性群で低かった(P<0.001)。また、遊離癌細胞陽性群の5年全生存率は65.8%、陰性群は86.6%とこちらも陽性群で有意に低かった(P=0.014)。22例の肺門リンパ節転移陽性症例に対象を絞ると、遊離癌細胞陽性群の5年無再発生存率は0.0%、陰性群は53.8%と陽性群で有意に低く(P=0.006)、遊離癌細胞陽性群の5年全生存率は53.3%、陰性群は69.2%と陽性群で低い傾向にあった(P=0.463)。本研究より、病理病期I/II期非小細胞肺癌症例において、遊離癌細胞の発現は、予後不良と関連があることが分かった。また、肺門リンパ節転移症例においては、遊離癌細胞の発現は、癌再発の有用なマーカーになる可能性があることが示唆された。
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Freely floating cancer cells in lymph node sinuses of hilar lymph node
positive non-small cell lung cancer patients.
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Abstract. |
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Previous studies demonstrated that freely floating cancer cells (FFCCs)
in the lymph node sinuses were of prognostic significance for colorectal
and gastric cancers. We investigated the clinical significance of detecting
FFCCs using Fast Red staining for cytokeratin in both stage I/II non-small
cell lung cancer (NSCLC) patients and hilar lymph node positive NSCLC patients
who underwent curative resection. Between 2002 and 2011, a total of 164
patients ( including 22 hilar lymph node positive patients) were investegated.
Resected lymph nodes were stained for cytokeratin using an anti-cytokeratin
antibody. In order to achieve a clear distinction from coal dust, an anti-cytokeratin
antibody was labeled with a secondary antibody conjugated with alkaline
phosphatase, which was detected by a reaction with Fast Red/naphthol that
produced a red color. Patients were considered to be positive for FFCCs
(FFCCs+) if one or more than one freely floating cytokeratin-positive cells
were detected in the lymph node sinuses which could not be detected by
hematoxylin and eosin stainig. Among all 164 patients, a significant difference
was observed in five-year relapse-free survival rates (5Y-RFS), with 76.9%
and 33.3% being achieved by FFCCs- and FFCCs+ patients, respectively (P<0.001).
Similarly, the 5-year overall survival rate (5Y-OS) was significantly lower
in FFCCs+ patients, with 86.6% being achieved by FFCCs- and 65.8% by FFCCs+
patients, respectively (P=0.014). Among 22 hilar lymph node positive patients,
a significant difference was also observed in 5Y-RFS, with 53.8% and 0.0%
being achieved by FFCCs- and FFCCs+ patients, respectively (P=0.006). The
5Y-OS tended to be lower in FFCCs+ patients, with 69.2% and 53.3% being
achieved by FFCCs- and FFCCs+ patients, respectively (P=0.463). The presence
of FFCCs in stage I/II NSCLC patients was associated with a poor prognosis.
In addition, FFCCs in hilar lymph node positive patients also have potential
as a useful marker foreseeing the recurrence.
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MOLECULAR MEDICINE REPORTS 18: 1081-1087, 2018
https://www.spandidos-publications.com/mmr/18/1/1081/abstract |
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東海大学医学部 “学生が選ぶ Best teacher賞” (2002年/2003年、計2回受賞) |
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東海大学総合研究機構/2007年度優秀研究ユニット賞受賞
消化器癌の転移・再発高危険群における抗癌剤(CPT-11/白金製剤)感受性に関する
臨床病理学的検討 |
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1) |
東海大学総合研究機構/1998年度研究奨励補助金
原発性大腸癌の転移・再発に対するMMP-2/TIMP-2の役割 |
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研究代表者:向井正哉 |
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The expression of MMP-2 and TIMP-2 in patients with colorectal adenocarcinoma
invaded to the submucosal and proper muscle layer.
Masaya Mukai他. Oncol Rep. 1998; 5: 335-340. |
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The expression of MMP-2 and TIMP-2 in patients with colorectal adenocarcinoma:
correlation with liver metastasis.
Masaya Mukai他. Oncol Rep. 6: 969-973, 1999. |
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東海大学総合研究機構/2003年度研究奨励補助金
原発性大腸癌の転移・再発高危険群に対するランダマイズド・プロスペクティブスタディ |
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研究代表者:向井正哉 |
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Occult neoplastic cells and malignant micro-aggregates in lymph node sinuses:
Review and hypothesis.
Masaya Mukai他. Oncol Rep. 14: 173-175, 2005. |
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Prospective study on the recurrence/metastasis of stage II/III colorectal
cancer and gastric cancer associated with occult neoplastic cells in lymph
node sinuses: Three-year interim results. Masaya Mukai他.
Oncol Rep. 16: 405-410, 2006. |
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3) |
東海大学総合研究機構/2005年度研究奨励補助金
消化器癌の転移・再発高危険群における抗癌剤(5-FU/LV)感受性に関する
臨床病理学的検討
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研究代表者:向井正哉 |
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Recurrence and 5-FU sensitivity of stage III/Dukes’ C colorectal cancer
with occult neoplastic cells in lymph node sinuses.
Masaya Mukai他. Oncol Rep. 14: 1165-1169, 2005. |
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Recurrence and 5-FU sensitivity of stage II/Dukes’ B colorectal cancer
with occult neoplastic cells in lymph node sinuses.
Masaya Mukai他. Oncol Rep. 14: 1171-1176, 2005. |
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東海大学総合研究機構/2007年度優秀研究ユニット賞
消化器癌の転移・再発高危険群における抗癌剤(CPT-11/白金製剤)感受性に関する
臨床病理学的検討 |
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研究代表者:向井正哉 |
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Sensitivity to CPT-11 and platinum derivatives of stage III/Dukes’ C colorectal
cancer with occult neoplastic cells in lymph node sinuses.
Masaya Mukai他. Oncol Rep. 17: 1027-1032, 2007. |
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Local recurrence and occult neoplastic cells in the extranodal fat of dissected
lymph nodes in patients with curatively resected primary colorectal cancer.
Masaya Mukai他. Oncol Rep. 17: 1365-1369, 2007. |
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5) |
その他・民間企業等からの特別委託研究費 2007-2011年度.
大腸癌/胃癌の転移・再発に関する臨床病理学的研究 |
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研究代表者:向井正哉 |
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