今日の臨床サポート

大腸癌

著者: 猪股雅史 大分大学医学部 消化器・小児外科学講座

監修: 杉原健一 東京医科歯科大学大学院

著者校正/監修レビュー済:2021/11/02
参考ガイドライン:
  1. 大腸癌研究会:大腸癌治療ガイドライン2019年版
患者向け説明資料

概要・推奨   

  1. 内視鏡的摘除をされpSM癌と診断された場合は、垂直断端に癌を認めれば外科手術を、それ以外の場合は病理所見に基づいて、経過観察を行うか、外科的切除を考慮する(推奨度2・エビデンスレベルB)。
  1. 切除不能な遠隔転移例における原発巣切除は、他の療法では制御困難な原発巣による症状があり、過大侵襲とならない切除であれば、原発巣を切除して全身薬物療法を行うことを強く推奨する(推奨度1・エビデンスレベルC)。
  1. 限局性播種(P1、P2)で、過大侵襲とならない切除であれば、原発巣と同時に腹膜転移を切除することを強く推奨する(推奨度1・エビデンスレベルC)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に はご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご 契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
閲覧にはご契
閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧に
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が
  1. 閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
猪股雅史 : 講演料(オリンパス(株),コヴィディエンジャパン(株),ジョンソン・エンド・ジョンソン(株)),研究費・助成金など((株)アデランス,(株)日田天領水)[2021年]
監修:杉原健一 : 講演料(大鵬薬品)[2021年]

改訂のポイント:
  1. 薬剤の適応承認について情報の追加を行った。

病態・疫学・診察

疾患情報  
  1. 大腸癌とは、大腸(盲腸、結腸、直腸)に発生する悪性腫瘍である。日本において、大腸癌の罹患数・死亡数はともに増加しており、2015年の罹患数はワースト1位、死亡数は肺癌に次いでワースト2位である。また2020年の罹患率に関して、男性は肺癌に次いでワースト2位、女性は乳癌に次いでワースト2位になると予想されている。
  1. 50歳過ぎから年齢とともに罹患率が高まる。
  1. 大腸癌の90%以上は腺癌である。大腸癌の発生部位としては、「結腸」と「直腸」の比がおおむね2:1となっている。S状結腸癌と直腸癌だけで全体の半分近くを占める。また大腸癌では同時性多発癌を3~5%に認める。
  1. 大腸癌は、進行度によってStage 0 - Stage Ⅳに分類される(大腸癌取扱い規約[第8版])。
  1. Stage 0に対しては、内視鏡的切除術が行われる場合が多い。Stage Ⅰ~Ⅲに対しては外科的切除が行われ、リンパ節転移を有するStage Ⅲには術後補助化学療法が行われる。Stage Ⅳに対しては、肝転移や肺転移などが切除可能と判断される場合には外科的切除が行われる場合も多い。手術が不可能な場合には全身化学療法が施行される。
 
大腸癌のステージ分類

  1. 大腸癌取扱い規約によるステージ分類は、深達度とリンパ節転移、遠隔転移の状況で決まり、これら3要素を組み合わせて0、Ⅰ、Ⅱ、ⅢA、ⅢB、Ⅳの11段階に分類される。
  1. 大腸癌の肝転移、腹膜転移、肝・腹膜以外への遠隔転移:表<図表>
  1. 大腸癌の病期分類:表<図表>
  1. TX:壁深達度の評価ができない。
  1. T0:癌を認めない。
  1. Tis :癌が粘膜内(M)にとどまり、粘膜下層(SM)に及んでいない。
  1. T1:癌が粘膜下層(SM)までにとどまり、固有筋層(MP)に及んでいない。
  1. T1a:癌が粘膜下層(SM)までにとどまり、浸潤距離が1,000μm未満である。
  1. T1b:癌が粘膜下層(SM)までにとどまり、浸潤距離が1,000μm以上であるが固有筋層(MP)に及んでいない。
  1. T2:癌が固有筋層(MP)まで浸潤し、これを超えていない。
  1. T3:癌が固有筋層を超えて浸潤している。
  1. 漿膜を有する部位では、癌が漿膜下層(SS)までにとどまる。
  1. 漿膜を有しない部位では、癌が外膜(A)までにとどまる。
  1. T4:癌が漿膜表面に接しているかまたは露出(SE)、あるいは直接他臓器に浸潤している(SI/AI)。
  1. T4a:癌が漿膜表面に接しているか、またはこれを破って腹腔に露出している(SE)。
  1. T4b:癌が直接他臓器に浸潤している(SI/AI)。

 
2型進行大腸癌

出典

img1:  金光幸秀先生ご提供
 
 
問診・診察のポイント  
  1. 大腸癌は病期と占拠部位によって症状が異なるため、全身症状を含めた問診が必要となる。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Andrew G Renehan, Matthias Egger, Mark P Saunders, Sarah T O'Dwyer
雑誌名: BMJ. 2002 Apr 6;324(7341):813.
Abstract/Text OBJECTIVE: To review the evidence from clinical trials of follow up of patients after curative resection for colorectal cancer.
DESIGN: Systematic review and meta-analysis of randomised controlled trials of intensive compared with control follow up.
MAIN OUTCOME MEASURES: All cause mortality at five years (primary outcome). Rates of recurrence of intraluminal, local, and metastatic disease and metachronous (second colorectal primary) cancers (secondary outcomes).
RESULTS: Five trials, which included 1342 patients, met the inclusion criteria. Intensive follow up was associated with a reduction in all cause mortality (combined risk ratio 0.81, 95% confidence interval 0.70 to 0.94, P=0.007). The effect was most pronounced in the four extramural detection trials that used computed tomography and frequent measurements of serum carcinoembryonic antigen (risk ratio 0.73, 0.60 to 0.89, P=0.002). Intensive follow up was associated with significantly earlier detection of all recurrences (difference in means 8.5 months, 7.6 to 9.4 months, P<0.001) and an increased detection rate for isolated local recurrences (risk ratio 1.61, 1.12 to 2.32, P=0.011).
CONCLUSIONS: Intensive follow up after curative resection for colorectal cancer improves survival. Large trials are required to identify which components of intensive follow up are most beneficial.

PMID 11934773  BMJ. 2002 Apr 6;324(7341):813.
著者: Alvaro Figueredo, R Bryan Rumble, Jean Maroun, Craig C Earle, Bernard Cummings, Robin McLeod, Lisa Zuraw, Caroline Zwaal, Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care
雑誌名: BMC Cancer. 2003 Oct 6;3:26. doi: 10.1186/1471-2407-3-26. Epub 2003 Oct 6.
Abstract/Text BACKGROUND: A systematic review was conducted to evaluate the literature regarding the impact of follow-up on colorectal cancer patient survival and, in a second phase, recommendations were developed.
METHODS: The MEDLINE, CANCERLIT, and Cochrane Library databases, and abstracts published in the 1997 to 2002 proceedings of the annual meeting of the American Society of Clinical Oncology were systematically searched for evidence. Study selection was limited to randomized trials and meta-analyses that examined different programs of follow-up after curative resection of colorectal cancer where five-year overall survival was reported. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee.
RESULTS: Six randomized trials and two published meta-analyses of follow-up were obtained. Of six randomized trials comparing one follow-up program to a more intense program, only two individual trials detected a statistically significant survival benefit favouring the more intense follow-up program. Pooling of all six randomized trials demonstrated a significant improvement in survival favouring more intense follow-up (Relative Risk Ratio 0.80 (95%CI, 0.70 to 0.91; p = 0.0008). Although the rate of recurrence was similar in both of the follow-up groups compared, asymptomatic recurrences and re-operations for cure of recurrences were more common in patients with more intensive follow-up. Trials including CEA monitoring and liver imaging also had significant results, whereas trials not including these tests did not.
CONCLUSION: Follow-up programs for patients with curatively resected colorectal cancer do improve survival. These follow-up programs include frequent visits and performance of blood CEA, chest x-rays, liver imaging and colonoscopy, however, it is not clear which tests or frequency of visits is optimal. There is a suggestion that improved survival is due to diagnosis of recurrence at an earlier, asymptomatic stage which allows for more curative resection of recurrence. Based on this evidence and consideration of the biology of colorectal cancer and present practices, a guideline was developed. Patients should be made aware of the risk of disease recurrence or second bowel cancer, the potential benefits of follow-up and the uncertainties requiring further clinical trials. For patients at high-risk of recurrence (stages IIb and III) clinical assessment is recommended when symptoms occur or at least every 6 months the first 3 years and yearly for at least 5 years. At the time of those visits, patients may have blood CEA, chest x-ray and liver imaging. For patients at lower risk of recurrence (stages I and Ia) or those with co-morbidities impairing future surgery, only visits yearly or when symptoms occur. All patients should have a colonoscopy before or within 6 months of initial surgery, and repeated yearly if villous or tubular adenomas >1 cm are found; otherwise repeat every 3 to 5 years. All patients having recurrences should be assessed by a multidisciplinary team in a cancer centre.

PMID 14529575  BMC Cancer. 2003 Oct 6;3:26. doi: 10.1186/1471-2407-3-2・・・
著者: Joe J Tjandra, Miranda K Y Chan
雑誌名: Dis Colon Rectum. 2007 Nov;50(11):1783-99. doi: 10.1007/s10350-007-9030-5.
Abstract/Text PURPOSE: This is a systematic review to evaluate the impact of various follow-up intensities and strategies on the outcome of patients after curative surgery for colorectal cancer.
METHODS: All randomized trials up to January 2007, comparing different follow-up intensities and strategies, were retrieved. Meta-analysis was performed by using the Forest plot review.
RESULTS: Eight randomized, clinical trials with 2,923 patients with colorectal cancer undergoing curative resection were reviewed. There was a significant reduction in overall mortality in patients having intensive follow-up (intensive vs. less intensive follow-up: 21.8 vs. 25.7 percent; P = 0.01). Regular surveillance with serum carcinoembryonic antigen (P = 0.0002) and colonoscopy (P = 0.04) demonstrated a significant impact on overall mortality. However, cancer-related mortality did not show any significant difference. There was no significant difference in all-site recurrence and in local or distant metastasis. Detection of isolated local and hepatic recurrences was similar. Intensive follow-up detected asymptomatic recurrence more frequently (18.9 vs. 6.3 percent; P < 0.00001) and 5.91 months earlier than less intensive follow-up protocol; these were demonstrated with all investigation strategies used. Intensive surveillance program detected recurrences that were significantly more amenable to surgical reresection (10.7 vs. 5.7 percent; P = 0.0002). The chance of curative reresection were significantly better with more intensive follow-up (24.3 vs. 9.9 percent; P = 0.0001), independent of the investigation strategies used.
CONCLUSIONS: Intensive follow-up after curative resection of colorectal cancer improved overall survival and reresection rate for recurrent disease. However, the cancer-related mortality was not improved and the survival benefit was not related to earlier detection and treatment of recurrent disease.

PMID 17874269  Dis Colon Rectum. 2007 Nov;50(11):1783-99. doi: 10.1007・・・
著者: M Jeffery, B E Hickey, P N Hider
雑誌名: Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002200. doi: 10.1002/14651858.CD002200.pub2. Epub 2007 Jan 24.
Abstract/Text BACKGROUND: It is common clinical practice to follow patients with colorectal cancer (CRC) for several years following their definitive surgery and/or adjuvant therapy. Despite this widespread practice there is considerable controversy about how often patients should be seen, what tests should be performed and whether these varying strategies have any significant impact on patient outcomes.
OBJECTIVES: To review the available evidence concerning the benefits of intensive follow up of colorectal cancer patients with respect to survival. Secondary endpoints include time to diagnosis of recurrence, quality of life and the harms and costs of surveillance and investigations.
SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, CANCERLIT, Cochrane Controlled Trials Register, Science Citation Index, conference proceedings, trial registers, reference lists and contact with experts in the field.
SELECTION CRITERIA: Only randomised controlled trials comparing different follow-up strategies for patients with non-metastatic CRC treated with curative intent were included.
DATA COLLECTION AND ANALYSIS: Trial eligibility and methodological quality were assessed independently by the three authors.
MAIN RESULTS: Eight studies were included in this update of the review. There was evidence that an overall survival benefit at five years exists for patients undergoing more intensive follow up OR was 0.73 (95% CI 0.59 to 0.91); and RD -0.06 (95% CI -0.11 to -0.02). The absolute number of recurrences was similar; OR was 0.91 (95% CI 0.75 to 1.10); and RD -0.02 (95% CI -0.06 to 0.02) and although the weighted mean difference for the time to recurrence was significantly reduced by -6.75 (95% CI -11.06 to -2.44) there was significant heterogeneity between the studies. Analyses demonstrated a mortality benefit for performing more tests versus fewer tests OR was 0.64 (95% CI 0.49 to 0.85), and RD -0.09 (95%CI -0.14 to -0.03) and liver imaging versus no liver imaging OR was 0.64 (95% CI 0.49 to 0.85), and RD -0.09 (95%CI -0.14 to -0.03). There were significantly more curative surgical procedures attempted in the intensively followed arm: OR 2.41(95% CI 1.63 to 3.54), RD 0.06 (95%CI 0.04 to 0.09). No useful data on quality of life, harms or cost-effectiveness were available for further analysis.
AUTHORS' CONCLUSIONS: The results of our review suggest that there is an overall survival benefit for intensifying the follow up of patients after curative surgery for colorectal cancer. Because of the wide variation in the follow-up programmes used in the included studies it is not possible to infer from the data the best combination and frequency of clinic (or family practice) visits, blood tests, endoscopic procedures and radiological investigations to maximise the outcomes for these patients. Nor is it possible to estimate the potential harms or costs of intensifying follow up for these patients in order to adopt a cost-effective approach in this clinical area. Large clinical trials underway or about to commence are likely to contribute valuable further information to clarify these areas of clinical uncertainty.

PMID 17253476  Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002200. d・・・
著者: Hideki Ueno, Hidetaka Mochizuki, Yojiro Hashiguchi, Hideyuki Shimazaki, Shinsuke Aida, Kazuo Hase, Susumu Matsukuma, Tadao Kanai, Hiroyuki Kurihara, Kotaro Ozawa, Kazuyoshi Yoshimura, Shinya Bekku
雑誌名: Gastroenterology. 2004 Aug;127(2):385-94.
Abstract/Text BACKGROUND & AIMS: Various histologic findings exist for managing patients with malignant polyps. Our goal was to determine the criteria for a conservative approach to patients with locally excised early invasive carcinoma.
METHODS: In 292 early invasive tumors (local resection followed by laparotomy [80 tumors, group A], local resection only [41 tumors, group B], and primarily laparotomy [171 tumors, group C], potential parameters for nodal involvement were analyzed. The status of the endoscopic resection margin also was examined for the risk for intramural residual tumor.
RESULTS: Unfavorable tumor grade, definite vascular invasion, and tumor budding were the combination of qualitative factors that most effectively discriminated the risk for nodal involvement in patients in groups A-C. The nodal involvement rate was 0.7%, 20.7%, and 36.4% in the no-risk, single-risk, and multiple-risks group, respectively. Thirty-two and 9 patients from group B were assigned to the no-risk and one-risk group, respectively; extramural recurrence occurred in 2 patients with risk factors. Considering quantitative risk parameters for submucosal invasion (i.e., width > or =4000 microm or depth > or =2000 microm), nodal involvement (including micrometastases) was not observed in the redefined no-risk group that accounted for about 25% of the patients from groups A and C. An insufficiency of endoscopic resection could be evaluated most precisely based on the coagulation-involving tumor, rather than the 1-mm rule for the resection margin.
CONCLUSIONS: Provided that the criterion of sufficient excision is satisfied, the absence of an unfavorable tumor grade, vascular invasion, tumor budding, and extensive submucosal invasion would be the strict criteria for a wait-and-see policy.

PMID 15300569  Gastroenterology. 2004 Aug;127(2):385-94.
著者: Kazuaki Kitajima, Takahiro Fujimori, Shigehiko Fujii, Jun Takeda, Yasuo Ohkura, Hitoshi Kawamata, Toshihide Kumamoto, Shingo Ishiguro, Yo Kato, Tadakazu Shimoda, Akinori Iwashita, Yoichi Ajioka, Hidenobu Watanabe, Toshiaki Watanabe, Tetsuichiro Muto, Ko Nagasako
雑誌名: J Gastroenterol. 2004 Jun;39(6):534-43. doi: 10.1007/s00535-004-1339-4.
Abstract/Text BACKGROUND: Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC.
METHODS: SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt's classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined.
RESULTS: For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 micro m if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 micro m.
CONCLUSIONS: These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.

PMID 15235870  J Gastroenterol. 2004 Jun;39(6):534-43. doi: 10.1007/s0・・・
著者: Al B Benson, Deborah Schrag, Mark R Somerfield, Alfred M Cohen, Alvaro T Figueredo, Patrick J Flynn, Monika K Krzyzanowska, Jean Maroun, Pamela McAllister, Eric Van Cutsem, Melissa Brouwers, Manya Charette, Daniel G Haller
雑誌名: J Clin Oncol. 2004 Aug 15;22(16):3408-19. doi: 10.1200/JCO.2004.05.063. Epub 2004 Jun 15.
Abstract/Text PURPOSE: To address whether all medically fit patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice, to identify patients with poor prognosis characteristics, and to describe strategies for oncologists to use to discuss adjuvant chemotherapy in practice.
METHODS: An American Society of Clinical Oncology Panel, in collaboration with the Cancer Care Ontario Practice Guideline Initiative, reviewed pertinent information from the literature through May 2003.
RESULTS: A literature-based meta-analysis found no evidence of a statistically significant survival benefit of adjuvant chemotherapy for stage II patients. Recommendations The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology.
CONCLUSION: Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.

PMID 15199089  J Clin Oncol. 2004 Aug 15;22(16):3408-19. doi: 10.1200/・・・
著者: E J D Van Cutsem, J Oliveira, ESMO Guidelines Working Group
雑誌名: Ann Oncol. 2008 May;19 Suppl 2:ii29-30. doi: 10.1093/annonc/mdn077.
Abstract/Text
PMID 18456758  Ann Oncol. 2008 May;19 Suppl 2:ii29-30. doi: 10.1093/an・・・
著者: P H Sugarbaker
雑誌名: Ann Surg. 1995 Jan;221(1):29-42.
Abstract/Text OBJECTIVE: New surgical procedures designed to assist in the treatment of peritoneal surface malignancy were sought.
BACKGROUND: Decisions regarding the treatment of cancer depend on the anatomic location of the malignancy and the biologic aggressiveness of the disease. Some patients may have isolated intra-abdominal seeding of malignancy of limited extent or of low biologic grade. In the past, these clinical situations have been regarded as lethal.
METHODS: The cytoreductive approach may require six peritonectomy procedures to resect or strip cancer from all intra-abdominal surfaces.
RESULTS: These are greater omentectomy-splenectomy; left upper quadrant peritonectomy; right upper quadrant peritonectomy; lesser omentectomy-cholecystectomy with stripping of the omental bursa; pelvic peritonectomy with sleeve resection of the sigmoid colon; and antrectomy.
CONCLUSIONS: Peritonectomy procedures and preparation of the abdomen for early postoperative intraperitoneal chemotherapy were described. The author has used the cytoreductive approach to achieve long-term, disease-free survival in selected patients with peritoneal carcinomatosis, peritoneal sarcomatosis or mesothelioma.

PMID 7826158  Ann Surg. 1995 Jan;221(1):29-42.
著者: S R Pestieau, P H Sugarbaker
雑誌名: Dis Colon Rectum. 2000 Oct;43(10):1341-6; discussion 1347-8.
Abstract/Text PURPOSE: The initial dissemination of colon cancer occurs through three routes: the lymphatics, the portal blood, and the peritoneal surfaces. Although lymphatic and hematogenous metastases indicate an aggressive disease process, it is possible that dissemination to peritoneal surfaces may be only superficial contamination of the parietal and visceral peritoneum that may be treatable for cure. Unfortunately, surgery may have an adverse impact on peritoneal surface dissemination. Surgical interventions may convert a superficial process into an invasive condition with a greatly reduced prognosis. This study was conducted to test this hypothesis by the use of data prospectively recorded from patients treated for peritoneal carcinomatosis concomitant with resection of the primary colon cancer or treated for carcinomatosis after disease recurrence prompted referral.
METHODS: Our first group of patients had definitive treatment of carcinomatosis simultaneous with resection of the primary colon cancer. They had cytoreductive surgery including peritonectomy procedures followed by heated intraoperative intraperitoneal chemotherapy with mitomycin C plus early postoperative intraperitoneal 5-fluorouracil. The comparison group was treated with a colon resection at an outside hospital and then later referred to us with progressive disease for treatment. The major difference between the groups is the timing of the definitive treatment of carcinomatosis. These patients were also studied by use of the completeness of the cytoreduction score and the peritoneal cancer index as prognostic indicators. Survival was the end point for all the analysis.
RESULTS: Of 104 patients with peritoneal carcinomatosis from colon or rectal adenocarcinoma, five patients (4.8 percent) had definitive treatment of the peritoneal surface spread of the cancer concomitant with resection of the primary lesion. Median survival for these patients has not been reached and their five-year survival rate is 100 percent. The remainder of the patients (n = 99) were referred for local and regional recurrence after their primary cancer had been removed and there was progression of carcinomatosis. Forty-four patients (42.3 percent) had a complete cytoreduction resulting in a 24-month median survival and a 30 percent five-year survival (P < 0.0001). The other 55 patients (52.9 percent) had an incomplete cytoreduction resulting in a 12-month median survival and a 0 percent five-year survival (P < 0.0001). Patients with a peritoneal cancer index of 10 or less had a 48-month median survival and a 50 percent five-year survival rate. Patients with a peritoneal cancer index between 11 and 20 had a 24-month median survival and a 20 percent five-year survival rate (P < 0.0001). Patients with a peritoneal cancer index of more than 20 had a 12-month median survival and a 0 percent five-year survival (P < 0.0001).
CONCLUSIONS: In patients with peritoneal seeding occurring at the time of resection of the primary malignancy, peritonectomy procedures and perioperative intraperitoneal chemotherapy should be performed concomitantly. By use of a quantitative scoring system, the mass of cancer present in the abdomen and pelvis at the time of treatment of carcinomatosis correlated directly with survival. Aggressive treatment of patients with peritoneal carcinomatosis requires consideration in the management of colorectal cancer.

PMID 11052509  Dis Colon Rectum. 2000 Oct;43(10):1341-6; discussion 13・・・
著者: Hirotoshi Kobayashi, Kenjiro Kotake, Kenichi Sugihara
雑誌名: Int J Clin Oncol. 2014 Feb;19(1):98-105. doi: 10.1007/s10147-012-0505-6. Epub 2012 Dec 13.
Abstract/Text BACKGROUND: Preoperative detection of small peritoneal metastases is difficult, and a convenient method is required to decide the nature of procedures subsequent to initial exploratory surgery. The aim of this study was to validate the Japanese classification of peritoneal metastasis from colorectal cancer.
METHODS: This retrospective study analyzes data from a multi-center registry. Factors affecting the extent of peritoneal metastasis, macroscopic radical resection and prognosis were analyzed using data from patients with colorectal cancer and synchronous peritoneal metastasis. Peritoneal metastasis was classified depending on extent into three groups (P1-P3).
RESULTS: Among 60,176 patients with colorectal surgery, 3,075 (5.1 %) had synchronous peritoneal metastasis. Tumor location on the right side (P < 0.0001), histological grade (P = 0.0014) and distant metastasis (P < 0.0001) were associated with the extent of peritoneal metastasis. Gender (P = 0.041), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis according to the present classification (P < 0.0001) and the period when the patient underwent the operation (operative period; P < 0.0001) were independently associated with macroscopic radical resection. Cox proportional hazards model disclosed that gender (P = 0.0046), tumor location (P = 0.032), age (P = 0.048), histological grade (P < 0.0001), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis (P < 0.0001), and macroscopic radical resection (P < 0.0001) were independent prognostic factors.
CONCLUSIONS: Macroscopic radical resection was an independent prognostic factor even without hyperthermic intraperitoneal chemotherapy. The referral of patients without distant metastasis to centers with experienced peritoneal surgeons might be a potential option if the peritoneal metastasis is unresectable in general hospitals.

PMID 23239055  Int J Clin Oncol. 2014 Feb;19(1):98-105. doi: 10.1007/s・・・
著者: Hirotoshi Kobayashi, Kenjiro Kotake, Kimihiko Funahashi, Kazuo Hase, Koichi Hirata, Tsuneo Iiai, Shingo Kameoka, Yukihide Kanemitsu, Koutarou Maeda, Akihiko Murata, Masayuki Ohue, Kazuo Shirouzu, Keiichi Takahashi, Toshiaki Watanabe, Hideaki Yano, Toshimasa Yatsuoka, Yojiro Hashiguchi, Kenichi Sugihara, Study Group for Peritoneal Metastasis from Colorectal Cancer by the Japanese Society for Cancer of the Colon and Rectum
雑誌名: J Gastroenterol. 2014 Apr;49(4):646-54. doi: 10.1007/s00535-013-0820-3. Epub 2013 Jun 24.
Abstract/Text BACKGROUND: Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis.
METHODS: We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum.
RESULTS: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1-P2, p = 0.0024) and absence of hematogenous metastases (p < 0.0001) were associated with R0 resection.
CONCLUSIONS: P1-P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.

PMID 23793379  J Gastroenterol. 2014 Apr;49(4):646-54. doi: 10.1007/s0・・・
著者: H J Wanebo, R J Koness, M P Vezeridis, S I Cohen, D E Wrobleski
雑誌名: Ann Surg. 1994 Oct;220(4):586-95; discussion 595-7.
Abstract/Text OBJECTIVE: The authors describe their experience with pelvic resection of recurrent rectal cancer with emphasis on patient selection for curative intent based on known tumor risk factors.
SUMMARY BACKGROUND DATA: Pelvic recurrence is a formidable problem in 30% of patients who have undergone a curative resection of primary rectal cancer. Although radiation can reduce the development of local recurrence and can provide palliation to many patients with localized disease, it is not curative. The authors and others have used the technique of abdominal sacral resection (ABSR) with or without pelvic exenteration to resect pelvic recurrence and its musculoskeletal extensions in selected patients with satisfactory long-term survival.
METHODS: The technique of ABSR with or without pelvic exenteration or resection of pelvic viscera, which the authors have described previously, was used in 53 patients with recurrent rectal cancer--47 patients for curative intent and 6 for palliation. Previous surgeries were abdominal perineal resections (APRs) in 26 patients, anterior resections in 19 patients, and other procedures in 2 patients; original primary Dukes' stage was B in 52% and C in 48%. Almost all patients had been irradiated previously, generally in the 4000 to 5900 cGy range. Preoperative carcinoembryonic antigen (CEA) levels (before ABSR) were elevated (> 5 ng/mL) in 54%.
RESULTS: Postoperative morbidity was encountered in most patients. Mortality was 8.5% in the curative group. Long-term survival for 4 years was achieved in 14 of 43 patients (33%), and 10 patients were alive with an acceptable quality of life after 5 years. Patients who had previous anterior resections or whose preoperative CEA levels were less than 10 ng/mL had a survival rate of approximately 45%, whereas patients with previous APRs and preoperative CEA levels greater than 10 ng/mL had a survival rate of only 15% to 18%. Patients with bone marrow invasion, positive margins, or pelvic node metastases had a median survival of only 10 months.
CONCLUSIONS: Pelvic recurrence of rectal cancer can be resected safely with expectation of long-term survival of 33%. Patient selection based on known risk factors can identify patients most likely to benefit from resection and eliminate those who should be treated for palliation only.

PMID 7524455  Ann Surg. 1994 Oct;220(4):586-95; discussion 595-7.
著者: O A Ogunbiyi, K McKenna, E H Birnbaum, J W Fleshman, I J Kodner
雑誌名: Dis Colon Rectum. 1997 Feb;40(2):150-5.
Abstract/Text OBJECTIVE: The purpose of this study was to determine whether radical surgery in appropriately selected patients who have recurrent rectal cancer can produce significant disease-free survival.
PATIENTS AND METHODS: This is a retrospective review of the management of all patients presenting with recurrent local and metastatic rectal cancer at a single institution during an 11-year period.
RESULTS: Of 489 patients who underwent curative surgery for primary rectal cancer during the period reviewed, 44 (9 percent) developed recurrent disease at a median interval of 18 (range, 3-60) months after curative surgery. Local pelvic recurrence alone was present in 28 (5.7 percent) patients. Overall survival after diagnosis of recurrent disease was 41 percent (18/44) at a median interval of 15 (range, 2-60) months. Curative resection was performed in 14 (32 percent) patients with a disease-free survival of 86 percent (12/14) at a median of 25 (range, 9-60) months after curative surgery. In comparison, survival in patients who underwent palliative treatment was significantly less (25 vs. 12 months; P < 0.05; 95 percent confidence interval, 10, 23 (Mann-Whitney U test)); 20 percent survival at a median of 12 months ranged from 2 to 36 after diagnosis of recurrent disease. Of six patients in the curative group who developed second recurrences, four underwent further curative surgery and are disease-free at a median of 19.5 (range, 12-29) months after surgery. Palliative surgery provided good symptomatic relief and improved quality of life in 11 patients in the palliative group, although there was no survival advantage over those who underwent nonsurgical palliative treatment (n = 19).
CONCLUSION: In appropriately selected cases, aggressive surgical therapy produces significant disease-free survival in patients with recurrent rectal cancer.

PMID 9075748  Dis Colon Rectum. 1997 Feb;40(2):150-5.
著者: Antonio M Lacy, Juan C García-Valdecasas, Salvadora Delgado, Antoni Castells, Pilar Taurá, Josep M Piqué, Josep Visa
雑誌名: Lancet. 2002 Jun 29;359(9325):2224-9. doi: 10.1016/S0140-6736(02)09290-5.
Abstract/Text BACKGROUND: Although early reports on laparoscopy-assisted colectomy (LAC) in patients with colon cancer suggested that it reduces perioperative morbidity, its influence on long-term results is unknown. Our study aimed to compare efficacy of LAC and open colectomy (OC) for treatment of non-metastatic colon cancer in terms of tumour recurrence and survival.
METHODS: From November, 1993, to July, 1998, all patients with adenocarcinoma of the colon were assessed for entry in this randomised trial. Adjuvant therapy and postoperative follow-up were the same in both groups. The main endpoint was cancer-related survival. Data were analysed according to the intention-to-treat principle.
FINDINGS: 219 patients took part in the study (111 LAC group, 108 OC group). Patients in the LAC group recovered faster than those in the OC group, with shorter peristalsis-detection (p=0.001) and oral-intake times (p=0.001), and shorter hospital stays (p=0.005). Morbidity was lower in the LAC group (p=0.001), although LAC did not influence perioperative mortality. Probability of cancer-related survival was higher in the LAC group (p=0.02). The Cox model showed that LAC was independently associated with reduced risk of tumour relapse (hazard ratio 0.39, 95% CI 0.19-0.82), death from any cause (0.48, 0.23-1.01), and death from a cancer-related cause (0.38, 0.16-0.91) compared with OC. This superiority of LAC was due to differences in patients with stage III tumours (p=0.04, p=0.02, and p=0.006, respectively).
INTERPRETATION: LAC is more effective than OC for treatment of colon cancer in terms of morbidity, hospital stay, tumour recurrence, and cancer-related survival.

PMID 12103285  Lancet. 2002 Jun 29;359(9325):2224-9. doi: 10.1016/S014・・・
著者: Christopher M Schlachta, Joseph Mamazza, Eric C Poulin
雑誌名: Surg Endosc. 2007 Mar;21(3):396-9. doi: 10.1007/s00464-006-9042-6. Epub 2006 Nov 14.
Abstract/Text BACKGROUND: The large randomized trials reporting on laparoscopic versus open colon surgery for cancer have all excluded patients with transverse colon cancer lesions. This study was undertaken to review our experience with surgery for curable transverse colon cancer.
METHODS: A database of 938 laparoscopic colon resections performed between April 1991 and September 2004 was reviewed. Of 514 procedures for cancer, stage IV disease, mid to low rectal cancers, and total colectomies were excluded. On an intent-to-treat basis, outcomes of surgery for transverse colon lesions (TC) were compared with outcomes of segmental colon resections for other lesions (OC).
RESULTS: A total of 22 TC were resected compared with 285 OC. Patients with TC were similar to patients with OC in age, gender, weight, and body mass index (BMI). Cancer stage was equivalent between patients with TC (9 Stage I, 7 Stage II, 6 Stage III) and OC (66 Stage I, 126 Stage II, 93 Stage III, p = 0.170) as was tumor size. Patients with TC underwent 9 transverse colectomies, 12 extended right hemicolectomies, and 1 extended left hemicolectomy. Patients with OC underwent 126 right hemicolectomies, 24 left hemicolectomies, and 135 sigmoid colectomies or anterior resections. There were no differences in conversion rate (18.2% vs. 13.3%, p = 0.752) or in intraoperative (9% vs. 8%, p = 0.814) or postoperative (41% vs. 30%, p = 0.418) complications. Operating time was longer with TC (209 +/- 63 min vs. 176 +/- 60 min, p = 0.042) and lymph node harvest was higher (15.3 +/- 11.6 vs. 10.8 +/- 7.6, p = 0.011). At a median followup of 17.2 months and 17.1 months, respectively, there were two (9%) recurrences after resection of TC and 17 (6%) recurrences after resection of OC.
CONCLUSIONS: Laparoscopic resection of transverse colon cancers is technically feasible and not associated with a significantly higher rate of complications or conversions or with impaired oncologic outcomes compared with patients having segmental laparoscopic resections for other colon cancers. Operating time is longer.

PMID 17103274  Surg Endosc. 2007 Mar;21(3):396-9. doi: 10.1007/s00464-・・・
著者: Iván Arteaga González, Antonio Martín Malagón, Eudaldo M López-Tomassetti Fernández, Javier Arranz Durán, Hermógenes Díaz Luis, Angel Carrillo Pallares
雑誌名: Surg Laparosc Endosc Percutan Tech. 2006 Feb;16(1):8-11. doi: 10.1097/01.sle.0000202188.57537.07.
Abstract/Text To assess the results of laparoscopic colorectal surgery in patients who have previously undergone abdominal surgery. Between November 2002 and June 2004, 86 patients underwent laparoscopic surgery for colorectal disease at our hospital. Patients were divided into 2 groups depending on whether they had previously undergone abdominal surgery (previous surgery group, n = 27) or not (nonprevious surgery group, n = 59). Data were prospectively collected for statistical analyses of demographic, clinical, and histologic variables. Groups were comparable in age, body mass index, American Society of Anesthesiologists score, diagnosis, technique performed, and tumor size and distance to anal verge. There was no difference in perioperative complication rates. A higher conversion rate was found in the previous surgery group (26.1% vs. 5.1%, P = 0.02). In patients with tumor diseases, resection evaluations were no different regarding specimen length, distal and radial resection margins, or number of lymph nodes harvested. Laparoscopic colorectal surgery has proved to be a reliable technique for patients who have previously undergone abdominal surgery, its results comparable to those obtained with patients who have not.

PMID 16552371  Surg Laparosc Endosc Percutan Tech. 2006 Feb;16(1):8-11・・・
著者: Pierre J Guillou, Philip Quirke, Helen Thorpe, Joanne Walker, David G Jayne, Adrian M H Smith, Richard M Heath, Julia M Brown, MRC CLASICC trial group
雑誌名: Lancet. 2005 May 14-20;365(9472):1718-26. doi: 10.1016/S0140-6736(05)66545-2.
Abstract/Text BACKGROUND: Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale randomised trials to support its use. We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes.
METHODS: Between July, 1996, and July, 2002, we undertook a multicentre, randomised clinical trial in 794 patients with colorectal cancer from 27 UK centres. Patients were allocated to receive laparoscopic-assisted (n=526) or open surgery (n=268). Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins, proportion of Dukes' C2 tumours, and in-hospital mortality. Analysis was by intention to treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN74883561.
FINDINGS: Six patients (two [open], four [laparoscopic]) had no surgery, and 23 had missing surgical data (nine, 14). 253 and 484 patients actually received open and laparoscopic-assisted treatment, respectively. 143 (29%) patients underwent conversion from laparoscopic to open surgery. Proportion of Dukes' C2 tumours did not differ between treatments (18 [7%] patients, open vs 34 [6%], laparoscopic; difference -0.3%, 95% CI -3.9 to 3.4%, p=0.89), and neither did in-hospital mortality (13 [5%] vs 21 [4%]; -0.9%, -3.9 to 2.2%, p=0.57). Apart from patients undergoing laparoscopic anterior resection for rectal cancer, rates of positive resection margins were similar between treatment groups. Patients with converted treatment had raised complication rates.
INTERPRETATION: Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes. However, impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use.

PMID 15894098  Lancet. 2005 May 14-20;365(9472):1718-26. doi: 10.1016/・・・
著者: A P Stillwell, P G Buettner, Y H Ho
雑誌名: World J Surg. 2010 Apr;34(4):797-807. doi: 10.1007/s00268-009-0366-y.
Abstract/Text BACKGROUND There is no consensus regarding the appropriate management of asymptomatic and minimally symptomatic patients with stage IV colorectal cancer and irresectable metastases. METHODS A literature search was conducted on Medline and Embase. Outcome measures included: survival; postoperative morbidity and mortality; complications from the primary tumor and the need for surgery to manage complications; the likelihood of curative surgery after initial response to primary therapy; and length of hospital stay. Quantitative meta-analysis was performed where appropriate. RESULTS Eight retrospective studies, including 1,062 patients, met the criteria for inclusion in this study. Meta-analysis has shown an improvement in the survival of patients managed with palliative resection of their primary tumor, with an estimated standardized median difference of 6.0 months (standardized difference, 0.55; 95% confidence interval (CI), 0.29, 0.82; p < 0.001). Patients managed with chemotherapy alone were 7.3 times more likely to have a complication from the primary tumor (95% CI, 1.7, 34.4; p = 0.008). There was no difference in the response rates to chemotherapy, making metastatic disease amendable to curative resection (0.85; 95% CI 0.40, 1.8; p = 0.662). CONCLUSIONS To date, only retrospective data are available, showing that palliative resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV colorectal cancer is associated with longer survival. Resection of the primary tumor reduces the likelihood of complications from the primary tumor and avoids the need for emergency procedures.

PMID 20054541  World J Surg. 2010 Apr;34(4):797-807. doi: 10.1007/s002・・・
著者: Sabine Venderbosch, Johannes H de Wilt, Steven Teerenstra, Olaf J Loosveld, Aart van Bochove, Harm A Sinnige, Geert-Jan M Creemers, Margot E Tesselaar, Linda Mol, Cornelis J A Punt, Miriam Koopman
雑誌名: Ann Surg Oncol. 2011 Nov;18(12):3252-60. doi: 10.1245/s10434-011-1951-5. Epub 2011 Aug 6.
Abstract/Text BACKGROUND: In patients with metastatic colorectal cancer (mCRC) with an asymptomatic primary tumor, there is no consensus on the indication for resection of the primary tumor.
METHODS: A retrospective analysis was performed on the outcome of stage IV colorectal cancer (CRC) patients with or without resection of the primary tumor treated in the phase III CAIRO and CAIRO2 studies. A review of the literature was performed.
RESULTS: In the CAIRO and CAIRO2 studies, 258 and 289 patients had undergone a primary tumor resection and 141 and 159 patients had not, respectively. In the CAIRO study, a significantly better median overall survival and progression-free survival was observed for the resection compared to the nonresection group, with 16.7 vs. 11.4 months [P<0.0001, hazard ratio (HR) 0.61], and 6.7 vs. 5.9 months (P=0.004; HR 0.74), respectively. In the CAIRO2 study, median overall survival and progression-free survival were also significantly better for the resection compared to the nonresection group, with 20.7 vs. 13.4 months (P<0.0001; HR 0.65) and 10.5 vs. 7.8 months (P=0.014; HR 0.78), respectively. These differences remained significant in multivariate analyses. Our review identified 22 nonrandomized studies, most of which showed improved survival for mCRC patients who underwent resection of the primary tumor.
CONCLUSIONS: Our results as well as data from literature indicate that resection of the primary tumor is a prognostic factor for survival in stage IV CRC patients. The potential bias of these results warrants prospective studies on the value of resection of primary tumor in this setting; such studies are currently being planned.

PMID 21822557  Ann Surg Oncol. 2011 Nov;18(12):3252-60. doi: 10.1245/s・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから