deficient mismatch repair

  • 文章类型: Journal Article
    背景:由于术后并发症和生活质量(QOL)降低,治疗直肠癌面临挑战。最近的证据支持术前治疗后临床完全缓解(cCR)的患者的观察和等待(WW)方法。在这份报告中,我们讨论了一例使用pembrolizumab成功治疗了错配修复缺陷(dMMR)的转移性直肠癌。
    方法:一名患有dMMR直肠癌和单个肝转移的47岁男性患者接受了pembrolizumab作为新辅助治疗。经过10门课程,直肠病变达到cCR,提示选择WW方法。肝转移显示显著缩小;然而,怀疑存在残留肿瘤,导致转移瘤切除术.通过组织学检查确认病理完全反应(pCR)。在24个月的随访中,没有肿瘤再生长的证据,局部复发,或远处转移。
    结论:术前治疗后获得cCR的患者越来越多地接受WW策略。虽然使用免疫检查点抑制剂(ICIs)治疗的dMMR直肠癌患者的pCR已被证明,从成像中准确预测pCR仍然具有挑战性。这个案例说明了综合ICI治疗,手术干预,在dMMR转移性直肠癌的治疗中,WW方法可以有效地实现肿瘤安全性和QOL的改善。
    BACKGROUND: Treating rectal cancer presents challenges due to postoperative complications and reduced quality of life (QOL). Recent evidence supports the watch-and-wait (WW) approach for patients with a clinical complete response (cCR) following preoperative treatment. In this report, we discuss a case of metastatic rectal cancer with deficient mismatch repair (dMMR) treated successfully with pembrolizumab.
    METHODS: A 47-year-old male with dMMR rectal cancer and a single liver metastasis underwent treatment with pembrolizumab as neoadjuvant therapy. After 10 courses, the rectal lesion achieved cCR, prompting the selection of the WW approach. The liver metastasis showed significant shrinkage; however, the presence of a residual tumor was suspected, leading to a metastasectomy. A pathological complete response (pCR) was confirmed via histological examination. During a 24-month follow-up, there was no evidence of tumor regrowth, local recurrence, or distant metastasis.
    CONCLUSIONS: The WW strategy is increasingly accepted for patients achieving cCR after preoperative treatment. While pCR in dMMR rectal cancer patients treated with immune checkpoint inhibitors (ICIs) has been documented, accurately predicting pCR from imaging remains challenging. This case illustrates that integrating ICI therapy, surgical interventions, and the WW approach can effectively achieve both oncological safety and improved QOL in the treatment of dMMR metastatic rectal cancer.
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  • 文章类型: Case Reports
    不可切除的结肠癌提出了复杂的临床挑战。新辅助免疫疗法已显示出改善可切除性的潜力。此外,手术技术的进步,包括完整的结肠系膜切除术(CME)和中央血管结扎(CVL),有助于改善右侧结肠癌的预后。此病例报告旨在证明腹腔镜成功切除了最初出现的不可切除的结肠癌,怀疑十二指肠受累。
    方法:一名70岁女性患者出现不可切除的升结肠错配修复缺陷(dMMR)腺癌,怀疑十二指肠向内生长。pembrolizumab和ataluren的新辅助治疗产生了显著的反应,允许手术切除.CME腹腔镜右半结肠切除术,包括CVL,通过Pfannenstiel切口进行体内吻合和拔除,已执行。此外,在观察到没有腔内侵入后,十二指肠的浆膜层被剃光。术后,发生一过性胃轻瘫,但总体结果是有利的。
    该病例强调了免疫治疗在改善不可切除的dMMR结肠癌并怀疑累及周围器官的可切除性方面的潜力。新辅助治疗和先进手术技术的结合,例如带有CVL的CME,在实现有利的临床结果方面显示出希望。然而,需要进一步的研究在更大的患者队列中验证这种联合治疗方法的有效性和安全性.
    结论:成功的腹腔镜切除了十二指肠受累的最初不可切除的dMMR结肠癌,在新辅助免疫疗法之后,展示了有希望的结果。本案主张进一步探索新辅助治疗的疗效,加上先进的手术技术,治疗局部晚期右侧结肠癌。
    UNASSIGNED: Irresectable colon cancer presents a complex clinical challenge. Neoadjuvant immunotherapy has shown potential in improving resectability. Additionally, advancements in surgical techniques, including complete mesocolic excision (CME) with central vascular ligation (CVL), have contributed to better outcomes for right-sided colon cancer. This case report aims to demonstrate the successful laparoscopic resection of initial appearing irresectable colon cancer with suspected duodenal involvement.
    METHODS: A 70-year-old female presented with an irresectable mismatch repair deficient (dMMR) adenocarcinoma of the ascending colon with suspected duodenal ingrowth. Neoadjuvant treatment with pembrolizumab and ataluren resulted in a significant response, allowing for surgical resection. A laparoscopic right hemicolectomy with CME, including CVL, intracorporeal anastomosis and extraction through a Pfannenstiel incision, was performed. Additionally, the serosal layer of the duodenum was shaved after observing the absence of intraluminal invasion. Postoperatively, transient gastroparesis occurred, but overall outcomes were favourable.
    UNASSIGNED: This case emphasizes the potential of immunotherapy in improving resectability for irresectable dMMR colon cancer with suspected involvement of surrounding organs. The combination of neoadjuvant therapy and advanced surgical techniques, such as CME with CVL, shows promise in achieving favourable clinical outcomes. However, further studies are needed to validate the effectiveness and safety of this combined approach in a larger cohort of patients.
    CONCLUSIONS: The successful laparoscopic resection of initially irresectable dMMR colon cancer with duodenal involvement, following neoadjuvant immunotherapy, demonstrated promising outcomes. This case advocates for further exploration of neoadjuvant treatments\' efficacy, coupled with advanced surgical techniques, in managing locally advanced right-sided colon cancer.
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  • 文章类型: Journal Article
    Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status has been approved as a tissue-agnostic biomarker for immune checkpoint inhibitor therapy in patients with solid tumors. We report the case of an MSI-H/dMMR diffuse large B-cell lymphoma (DLBCL) identified by targeted gene sequencing (TGS). A 90-year-old female who presented with vaginal bleeding and a large mass in the upper vagina was diagnosed with germinal center-B-cell-like DLBCL, which recurred at the uterine cervix at 9 months after chemotherapy. Based on TGS of 121 lymphoma-related genes and the LymphGen algorithm, the tumor was classified genetically as DLBCL of EZB subtype. Mutations in multiple genes, including frequent frameshift mutations, were detected by TGS and further suggested MSI. The MSI-H/dMMR and loss of MLH1 and PMS2 expression were determined in MSI-fragment analysis, MSI real-time polymerase chain reaction, and immunohistochemical tests. This case demonstrates the potential diagnostic and therapeutic utility of lymphoma panel sequencing for DLBCL with MSI-H/dMMR.
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