Pathologic complete response of hepatoid adenocarcinoma of the stomach after chemo-immunotherapy: A rare case report and literature review
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Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant subtype of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. We present an exceedingly rare case of complete response after chemo-immunotherapy.A 48-year-old woman with highly elevated serum alpha-fetoprotein (AFP) level was found to have HAS verified by pathological examination based on gastroscopy. Computed tomography scan was done and TNM staging of the tumor was T4aN3aMx. Programmed cell death ligand-1 (PD-L1) immunohistochemistry was performed, revealing a negative PD-L1 expression. Chemo-immunotherapy including oxaliplatin plus S-1 and PD-1 inhibitor terelizumab was given to this patient for 2 months until the serum AFP level decreased from 748.5 to 12.9 ng/mL and the tumor shrank. D2 radical gastrectomy was then performed and histopathology of the resected specimen revealed that the cancerous cells had disappeared. Pathologic complete response (pCR) was achieved and no evidence of recurrence has been found after 1 year of follow-up.We, for the first time, reported an HAS patient with negative PD-L1 expression who achieved pCR from the combined chemotherapy and immunotherapy. Although no consensus has been reached regarding the therapy, it might provide a potential effective management strategy for HAS patient.Keywords:
Histopathology
Abstract Background: The use of oxaliplatin is increasing in colorectal cancer both in the metastatic and adjuvant setting. There is an increased recognition of hypersensitivity reactions (HSR) to oxaliplatin which is a potential barrier to the continued use of this drug in patients in whom benefits are observed. The aim of this retrospective review is to identify the incidence of HSR and the results of rechallenging patients with oxaliplatin. Methods and results: In 97 patients, we identified six patients with HSR (an incidence of 6.2%) There was a spectrum of reported symptoms with most occurring within minutes of infusion after a median of six doses of oxaliplatin. All these patients were rechallenged with oxaliplatin. Success was noted when oxaliplatin was administered over a prolonged rate of 6 h. The use of maximal premedications did not influence the outcome. Conclusions: Our experience confirms the need to be vigilant of HSR to oxaliplatin and to recognize idiosyncratic reactions. A feasible method to prevent the recurrence of HSR is to prolong the infusion rate without delaying or stopping effective treatment with oxaliplatin.
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背景・目的: oxaliplatin base の化学療法が大腸癌腹膜播種症例に与える影響について検討した。対象・方法: 2006 年1月～2012 年11 月の間に，腹膜播種陽性Stage IV 大腸癌と診断され，oxaliplatin base の化学療法を導入した49 例（oxaliplatin施行群）と，それ以前に5─FU 系の全身化学療法を施行した26 例（control 群）を対象。oxaliplatin 導入前後のoverall survival（OS）を比較。また，oxaliplatin 施行群のOS に関して臨床病理学的因子を共変量とし，単変量，多変量解析を行い，予後因子を検討した。結果: oxalplatin 施行群はcontrol 群より有意に生存期間が延長していた（中央値 20.5 か月 vs 11.7 か月，p＝0.04）。oxaliplatin 施行群におけるOS に対するfavorable factor として，70 歳以下（p＝0.03），原発巣切除（p＝0.02）が同定された。結語: oxaliplatin base の化学療法は大腸癌腹膜播種症例においても生存期間を改善させた。腹膜播種の程度に関係なく原発巣切除を70 歳以下の症例に行い，速やかにoxaliplatin base の化学療法を導入することが予後向上につながることが示唆された。
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OBJECTIVE To investigate the efficacy and safity of the domestic vs.imported oxaliplatin applied in advanced colon cancer.METHODS A total of 68 patients with advanced colon cancer were randomly divided into 2 groups : domestic oxaliplatin(50 mg) treatment group(the Ai Heng group,n=35) and imported oxaliplatin(50 mg) treatment group(Eloxatin group,n=33).All patients in both groups was adopted FOLFOX4 program(oxaliplatin combined with 5-fluorouracil and folinic acid).The adverse reactions and recent clinical efficacy were observed and a statistical analysis was conducted.RESULTS There were no significant difference in the recent clinical efficacy and chemotherapy-related adverse reactions between the two groups(P0.05).CONCLUSION Domestic oxaliplatin and the imported oxaliplatin are similar in anti-tumor efficacy and adverse reactions.Domestic oxaliplatin is safe and effective for advanced colon cancer.
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Background: Significant efficacy of oxaliplatin-based chemotherapy has been demonstrated for advanced gastric cancer (AGC). However, the appropriate dose of oxaliplatin, and the efficacy and toxicity of administration of oxaliplatin subsequent to cisplatin therapy still remain unclear. Patients and Methods: In total, 55 patients with AGC that were scheduled to receive oxaliplatin-based chemotherapy were prospectively examined. Results: The median age was 67 years and oxaliplatin was administered to 39 (71%) patients as first-line and in 16 (29%) patients as second-line therapy. An initial dose of 130 or 100 mg/m2 of oxaliplatin was administered to 11 and 36 patients, respectively. The overall response rates (ORR) and median progression free survival (mPFS) were 86 and 33%, and 7.2 and 7.8 months, respectively. Compared to 100 mg/m2, the relative dose intensity was significantly lower and severe toxicity tended to increase with oxaliplatin at 130 mg/m2. A total of 10 patients (18%) had a prior cisplatin-based therapy. The ORR of the patients pretreated with cisplatin was 14% and the mPFS was 6.1 months. Conclusion: An initial oxaliplatin dose of 130 mg/m2 resulted in a good response, but tended to increase the risk of toxicity. Subsequent oxaliplatin-based therapy after cisplatin exhibited modest efficacy, especially in cases with cisplatin intolerance.
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瞄准：在回顾的案例系列分析在变形 colorectal 癌症调查导致 oxaliplatin 的严重过敏反应的反应(SAR ) 并且进行全身的文学评论。方法：在在高雄老手医院将军的从 2006 ～ 2011 的 6 年的经期期间，暴露于 oxaliplatin 相关的化疗的 412 个病人的一个总数回顾地被考察。关于威胁生活的 SAR 后面的 oxaliplatin 的相关英语语言的研究也在 MEDLINE 被考察吗？并且 PubMed？搜索。结果：八个病人(1.9% ， 412 个案例中的 8 个) 被识别。七个病人是成功的没有任何 sequelae，复活了，一个病人到期了。我们在病人 3 在五个病人和重新质问的 oxaliplatin 使用改变了化疗政体。与 66 个病人一起的 23 相关英语语言的研究被报导。接待的病人一 oxaliplatin 的 10 个周期中部(变化， 2 ～ 29 ) 。最普通的症状是呼吸的悲痛(60%) ，发烧(55%) ，和低血压(54%) 。三个致命的事件被报导(4.5%) 。66 个案例的十一个病人(16%) 被 oxaliplatin 重新质问。结论：SAR 必须重重地在收到 oxaliplatin 相关的化疗的病人被考虑，在特别 pretreated 病人。oxaliplatin 相关的 SAR 的机制，预言者，预防方法和管理上的进一步的研究被推荐。
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［背景］Oxaliplatinは，日本で合成された第3 世代の白金錯体系の抗悪性腫瘍剤であり，欧米ではOxaliplatin と持続投与5-FU/LV 併用（FOLFOX 療法）が進行再発大腸癌に対する標準的な化学療法としての地位を確立し広く施行されている。本邦では，2005 年4 月にOxaliplatinが承認され，当院でも切除不能進行・再発大腸癌に対するfirst-lineの化学療法としてFOLFOX 療法を積極的に施行している。［方法］2005 年6 月より2007 年8 月までに切除不能進行・再発大腸癌に対し，first-line としてFOLFOX4 およびmFOLFOX6 を施行した23 例を対象とし，その効果・安全性を検討した。FOLFOX4 は13 例に，mFOLFOX6は10 例に施行された。［結果］奏効率は50.0％であり，全生存期間は17.4 か月であった。投与回数の中央値は8.0，Oxaliplatinのrelative dose intensityは74.5％である。有害事象は，血液毒性ではGrade 3 以上の白血球減少を4 例，好中球減少を12 例に認め，非血液毒性ではGrade 3 の消化器毒性を1 例，Grade 3 の末梢神経障害を1例に認めたのみであった。［結語］FOLFOX 療法は，日本人においても進行再発大腸癌に対するfirst-lineの化学療法として比較的高い奏効性と安全性をもつ治療法であることが確認された。
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oxaliplatin を含む化学療法により肝類洞障害が生じ，その結果，門脈圧が亢進し脾腫が生じる例があることが知られている。今回われわれは，oxaliplatin を含む化学療法により脾臓が増大し，oxaliplatin の休薬により縮小した大腸癌の2 例を報告する。なお脾臓体積の測定には医用画像処理ワークステーションZIOSTATION を用いた。ZIOSTATION 上で脾臓の3D 画像を作成し，その体積を測定した。症例1: 治療開始前137.82 mL であった脾臓はmFOLFOX6/bevacizumab による治療開始2 か月後160.96 mL に増大した。6 コース終了後神経障害のためoxaliplatin のみを休薬したところ151.58 mLに縮小した。神経障害改善後にoxaliplatin を再導入したところ脾臓は177.48 mL に増大したものの，再びoxaliplatin のみを休薬したところ158.52 mLに縮小した。症例2: 治療開始前105.84 mL であった脾臓はmFOLFOX6/bevacizumabによる治療開始10 か月後に228.54 mL に増大した。その後sLV5FU2/bevacizumab，さらにirinotecan 単剤へと移行したところ197.06 mL に縮小した。oxaliplatin 投与によって脾臓は増大するものの，oxaliplatin を休薬すれば脾臓の増大は可逆的である可能性がある。
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Aim: Cisplatin plus 5-fluorouracil (5-FU) or S-1 is a standard therapy for gastric cancer (GC). However, cisplatin is emetic and potentially nephrotoxic. Oxaliplatin may be less toxic, but few basic data are available for this setting. Here, we evaluated oxaliplatin for GC, by testing surgical specimens. Materials and Methods: We evaluated effects of oxaliplatin and 5-FU, alone and in combination, on surgical specimens from 11 patients with GC, using collagen gel droplet embedded culture drug tests. Results: Oxaliplatin was less efficacious than 5-FU, and its synergistic effect was less in tumors highly sensitive to 5-FU than in those with low sensitivity. Tumor differentiation and drug sensitivity were not correlated. Conclusion: Although oxaliplatin monotherapy had little effect on GC, we saw a limited synergistic effect of oxaliplatin with 5-FU in 5-FU-sensitive patients. Collagen gel droplet embedded culture drug tests may predict this synergistic effect, and help select candidates for this or other regimens.
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