肝胆膵
切除不能大腸癌肝転移に対するmFOLFOX6+セツキシマブ導入化学療法の有効性(NEXTO試験)
- 演 者：
- 宮田 明典1，長谷川 潔2, 斎浦 明夫3, 大場 大2, 山本 順司4, 野村 幸博1, 高山 忠利5,
橋口 陽二郎6, 柴崎 正幸7, 坂本 裕彦8, 三瀬 祥弘3, 篠崎 英司9, 吉田 俊太郎10,
野澤 宏彰11, 國土 典宏2,12 - 所属機関：
- 1総合病院国保旭中央病院・外科, 2東京大学附属病院・肝胆膵外科, 3がん研究会有明病院・肝胆膵外科, 4防衛医科大学校病院・肝胆膵外科, 5日本大学・消化器外科, 6帝京大学・消化器外科, 7東京山手メディカルセンター・消化器外科, 8埼玉県立がんセンター・消化器外科, 9がん研究会有明病院・消化器内科, 10東京大学附属病院・消化器内科, 11東京大学附属病院・腫瘍外科, 12国立国際医療研究センター病院・外科
Background: For colorectal liver metastasis (CRLM), surgical resection is now established as the standard treatment option. The recent advance of chemotherapy enables us to extend the surgical indication and improve prognosis in patients with technically/oncologically unresectable CRLM. Because mFOLFOX with cetuximab has been expected to provide early tumor shrinkage for CRLM with KRAS wild type, we conducted this phase II trial to prospectively evaluate the significance of the treatment strategy.
Methods: Patients having advanced CRLM (tumor number>=5 and/or technically unresectbale) with KRAS wild were included to this study. First, mFOLFOX with cetuximab was induced, and surgical indication was evaluated every 4 cycles (2 months). If all tumors including primary and/or metastatic colorectal carcinoma were regarded as technically resectable, we performed surgical resection after the waiting period of 1 month. If they were unresctable, we repeated the regimen within the upper limit of 12 cycles. The primary endpoint was R0 resection rate. The secondary endpoints included recurrence free survival (RFS), progression free survival (PFS), and overall survival (OS).
Results: Between May 2012 and May 2015, total 50 patients were enrolled to this trial in 14 centers. The induction was not done in 2 patients, who were excluded. The median age of the 48 patients was 62.5 (range: 45 to 79) including 36 men and 12 women. The median tumor number detected by CT before the induction was 12 (1 to 57). R0 and R1 resections were done with no mortality in 26 and 5 patients, respectively (R0 resection rate: 54.2%), whereas surgery was abandoned in 2. Under the median follow-up of 2.5 years, the 3-year RFS was 14.4%, 3-year PFS was 8.2%, 3-year OS was 60.0%, and median survival time was 3.4year.
Conclusions: For advanced CRLM with KRAS wild, mFOLFOX with cetuximab induction therapy provided the sufficient R0 resection rate and favorable OS.
肝門部領域胆管癌において腹腔洗浄細胞診を検討する意義はあるか
- 演 者：
- 中川 圭1，益田 邦洋1, 伊関 雅裕1, 高舘 達之1, 畠 達夫1, 有明 恭平1, 石田 晶玄1,
水間 正道1, 大塚 英郎1, 林 洋毅1, 森川 孝則1, 元井 冬彦1, 海野 倫明1 - 所属機関：
- 1東北大学・消化器外科
[Back ground]
For radical resection of perihilar cholangiocarcinoma, a highly invasive surgical operation is necessary. The 90-day mortality rate of these surgical procedures is reported to be 4.6 to 10.3% form Japanese National Clinical Database (NCD).
-Method-
We examined 296 cases of perihilar cholangiocarcinoma from 2006 to 2015 based on the prognosis including 101 non-resected cases and 195 resected cases undergoing peritoneal lavage cytology (pCY). The median survival time (MST) was calculated from the time of first visit.
-Result-
When examined with pN0, pN1, distant lymph node metastasis (pM1 (LYM)) and non-resected, MST were 71.9, 39.7, 16.6 and 16.7 months, respectively.
Resected cases of pM1(LYM) and non-resected were equivalent. Significant differences were observed in the 3 groups of pN0, pN1, non-resected (p<0.0001). Also, there was a significant difference between the 3 groups of pR0, pR1, and non-resected (p<0.0001).
As a prognostic factor, pM1 (LYM) (odds ratio 3.32, p <0.0001), peritoneal lavage cytology positive (3.99, p=0.0002), cT34/cT12 (2.00, p=0.0003), resection attempt No/Yes (6.93, p=0.0050) were candidates.
pCY positive cases (16 cases) included 12 cases of peritoneal dissemination (p <0.0001).
-Conclusion-
In the perihilar cholangiocarcinoma, it is important to select a scrutiny and a procedure to aim for pR0. Peritoneal lavage cytology (pCY) may detect potential peritoneal dissemination cases. Effective adjuvant chemotherapy does not exist currently. Therefore, in case of pCY positive, surgical operation must be inappropriate. We strongly recommend to confirm pCY0 after chemotherapy and to perform resection.
膵癌術前化学療法による腫瘍関連線維芽細胞と血管外活性化血小板への影響
- 演 者：
- 宮下 知治1，真橋 宏幸1, 岡崎 充善1, 大畠 慶直1, 中沼 伸一1, 牧野 勇1, 田島 秀浩1, 高村 博之1, 伏田 幸夫1, 太田 哲生1
- 所属機関：
- 1金沢大学・消化器・腫瘍・再生外科
Background: Extravasated platelet activation (EPA) associated with cancer-associated fibroblasts (CAFs) as well as pancreatic cancer cells was detected in our previous study. C-type lectin receptor (CLEC-2) has been identified as an endogenous receptor of podoplanin (PDPN) on platelets. The expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer. We investigated the effect of neoadjuvant therapy on EPA and PDPN -expression by CAFs using immunohistochemical analysis.
Materials and Methods: A total of 64 patients were enrolled in this study. We evaluated the expression of platelet specific marker (CD42b) and CAF marker (PDPN) using immunohistochemistry. Cases in which >10% of CD42b positive-CAFs were stained were defined as positive. Density of PDPN positive fibroblasts was determined by hybrid cell counting. This was compared to a group of untreated specimens, a group treated with conventional gemcitabine (GEM) alone, a group of GEM plus S-1 (GS) and a group of GEM plus Nab-paclitaxel (GnP).
Results: By immunohistochemistry CD42b expression was observed in 42 out of 64 (66%) patients surrounding CAFs. The expression of CD42b was observed in 11% of the GnP group. However, CD42b expression was detected in 71%, 63% and 78% in untreated, GEM alone and GS groups. There were significantly fewer CD42b expression in the GnP than in the untreated, GEM alone and GS groups. PDPN expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of PDPN -positive fibroblasts. There were significantly fewer PDPN -positive fibroblasts in the GnP than in the untreated, GEM alone and GS groups, but there was no significant difference between the latter 3 groups.
Conclusion: This data suggests that the GnP regimen decreases EPA in the stroma through PDPN -positive CAF depletion.
肝細胞癌切除患者におけるCONUTscoreの意義 -多施設共同研究の結果から-
- 演 者：
- 播本 憲史1,2，吉住 朋晴2, 足立 英輔3, 池田 泰治4, 内山 秀昭5, 宇都宮 徹6, 梶山 潔7, 木村 光一8, 岸原 文明9, 杉町 圭史10, 二宮 瑞樹11, 福澤 謙吾12, 前田 貴司13, 調 憲1, 前原 喜彦2
- 所属機関：
- 1群馬大学・肝胆膵外科, 2九州大学・消化器・総合外科, 3九州中央病院・外科, 4福岡市民病院・外科, 5福岡総合病院・外科, 6大分県立病院・外科, 7飯塚病院・外科, 8宗像医師会病院・外科, 9新日鐵八幡記念病院・消化器外科, 10九州がんセンター・肝胆膵外科, 11日本赤十字社松山赤十字病院・外科, 12日本赤十字社大分赤十字病院・外科, 13日本赤十字社広島赤十字・原爆病院・外科
Background: The Controlling Nutritional Status (CONUT) score is an objective tool widely used to assess nutritional status in patients with many cancer. The relationship between CONUT score and prognosis in patients who have undergone hepatic resection, however, has not been evaluated in multi-institutional study.
Methods: Data were retrospectively collected for 2461 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent at 13 institutions between January 2004 and December 2015. The patients were assigned to two groups, those with preoperative CONUT scores ≦3 (low CONUT score) and ≧4 (high CONUT score), and their clinicopathological characteristics, surgical outcomes, and long-term survival were compared using propensity score matching analysis.
Results: Of the 2461 patients, 540 (21.9%) had high (≧4) and1921 (78.1%) had low (≦3) preoperative CONUT scores. In the whole study series, high CONUT score was significantly associated with high age, female, low BMI, low serum albumin level, high serum total bilirubin level, low lymphocyte count, low serum cholesterol level, shorter prothrombin time, higher ICGR15, Child-Pugh B (vs. A), liver cirrhosis, non-anatomical resection shorter operation time, massive blood loss, blood transfusion and postoperative complication. After propensity score matching, higher CONUT score is significantly associated with poor overall survival and recurrent-free survival in multivariate analysis.
Conclusions:This retrospective and multi-institutional analysis showed that, in patients who undergo curative hepatectomy for HCC, preoperative CONUT score is predictive of poorer overall survival and recurrence-free survival even in propensity score matching analysis.
MRI拡散強調画像から見た肝内胆管癌の腫瘍悪性度に関する検討
- 演 者：
- 山田 眞一郎1，島田 光生1, 森根 裕二1, 居村 暁1, 池本 哲也1, 岩橋 衆一1, 齋藤 裕1, 和田 佑馬1, 良元 俊昭1, 太田 昇吾1
- 所属機関：
- 1徳島大学・外科学
Background:
Recently it has been reported that tumor malignancy can be estimated by an MRI diffusion weighted image (DWI), but there are no reports about intrahepatic colangiocarcinoma (IHCC). We examined a possibility of the prognostic prediction by signal intensity (SI) in MRI-DWI for IHCC.
Method:
twenty-eight patients who underwent hepatectomy for IHCC from 2004 to 2016 were enrolled in this study. DWI (b value:800mm/s) by MRI (GE Signa Excite™ and 1.5T, GE health care)was taken, and SI was mesured by ROI. Then, patients were divided into 2 groups; low SI group (SI<600,n=14) and high SI group (SI >= 600, n=14). Clinicopathological factors were compared between 2 groups.
Result:
There were no sgnificant difference in age, sex, tumor diameter, tumor occupied lesion, and tumor markers between 2 groups. However, stage was more advanced in high SI group. Overall survival rate and disease free survival rate were sgnificantly worse in high SI group (p<0.05). In univariate analysis for overall survival, hepatic hilar type (p=0.02), Stage III/IV (p=0.02), vp+ (p=0.05) and CA19-9>100U/ml (p=0.03) as well as DWI high SI(p=0.02) were identified as a prognostic factor. Furthermore, DWI high SI was identified as an independent prognostic factor by multivariate analysis (H.R.=5.78, 95% C.I. 1.23-42.2, p=0.03).
Conclusion
high SI in DWI was an independent prognostic factor in IHCC, and MRI may be also useful for prognostic prediction for IHCC, not only for tumor evaluation.
胆道癌術後の大量肝切除状態におけるGEMまたはS-1療法の第I/II相試験(KHBO1003/1208)
- 演 者：
- 小林 省吾1,2，永野 浩昭1,3, 波多野 悦朗4,5, 瀬尾 智4, 寺嶋 宏明6, 味木 徹夫7, 佐竹 悠良8, 亀井 敬子9, 藤山 泰二10, 廣瀬 哲朗11, 猪飼 伊和夫12, 竹村 茂一13, 柳本 泰明14, 森田 智視15, 井岡 達也2
- 所属機関：
- 1大阪大学・消化器外科, 2大阪国際がんセンター, 3山口大学・消化器・乳腺内分泌外科, 4京都大学・肝胆膵・移植外科, 5兵庫医科大学・外科, 6北野病院・消化器外科, 7神戸大学・肝胆膵外科, 8神戸市立医療センター中央市民病院・腫瘍内科, 9近畿大学・外科, 10愛媛大学・肝胆膵乳腺外科, 11日本赤十字社大津赤十字病院・外科, 12京都医療センター・外科, 13大阪市立大学・肝胆膵外科, 14関西医科大学・外科, 15京都大学・医学統計生物情報学
Backgrounds and aim:
Major hepatectomy may affect postoperative liver function and feasibility of adjuvant chemotherapy. We performed feasibility study of adjuvant chemotherapy (gemcitabine or s-1) after major hepatectomy due to biliary tract cancers (KHBO1003) and compared the effect of each chemotherapy (KHBO1208). These studies were performed as multicenter study and KHBO1208 study was supported by JSCO (Japan Society of Clinical Oncology) Clinical Research Grant Program 2012 and 2013; herein we show the results of these studies.
Methods:
We determined each recommended dose by the continual reassessment method in KHBO1003 phase I study and compared the feasibility and efficacy of each procedures with 10% alpha error and 20% beta error in KHBO1208 phase II study, and p values of <0.10 were considered to indicate a statistically significant difference.
Results:
KHBO1003 phase I study showed the following recommended dose: gemcitabine (1000 mg/m2) every 2 weeks or s-1 (80 mg/m2/day) for 28 days every 6 weeks. Seventy patients were enrolled in KHBO1208 phase II study and thirty-five patients were assigned to each arm. There were no statistically significant differences in the patient characteristics of the two arms. There were no statistically significant differences in the treatment completion rate and relative dose intensity of two arms. The comparison of the two arms revealed that overall survival curve of the s-1 arm were superior to gemcitabine (hazard ratio: 0.477).
Conclusion:
We completed Phase I/II study of adjuvant gemcitabine or s-1 therapy after major hepatectomy due to biliary tract cancer in multicenter study and showed the possible superiority of s-1 therapy.
