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纳武单抗和伊匹单抗治疗抗癌药耐药性微卫星高度不稳定降结肠癌后腹腔镜手术后的病理完全缓解:病例报告及文献综述

Pathologic complete response after laparoscopic surgery following treatment with nivolumab and ipilimumab for anticancer drug-resistant MSI-high descending colon cancer: a case report and literature review.

作者信息

Sawayama Hiroshi, Miyamoto Yuji, Ogawa Katsuhiro, Ohuchi Mayuko, Hisano Yuki, Kato Moeko, Tubakihara Hiroki, Yoshida Naoya, Baba Hideo

机构信息

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan.

Department of Surgery, Kumamoto General Hospital, 10-10, Toricho, Yatushiro, Kumamoto, 866-0856, Japan.

出版信息

Surg Case Rep. 2022 Dec 27;8(1):223. doi: 10.1186/s40792-022-01580-w.

Abstract

BACKGROUND

Preoperative treatment is performed for locally advanced colon cancer with extensive tumor proximity or suspected invasion of skeletal muscles, major organs, and blood vessels. Oxaliplatin-based regimens are often used in preoperative chemotherapy. However, microsatellite instability (MSI)-high colorectal cancer is often resistant to cytotoxic anticancer agents. Herein, we describe a case of treatment of anticancer drug-resistant MSI-high locally advanced colon cancer and review cases of complete response to immune checkpoint inhibitor therapy for colorectal cancer.

CASE PRESENTATION

A 57-year-old woman was referred to our hospital with a large tumor in the descending colon and extensive thoracic and abdominal wall involvement, including the ribs and diaphragm. No distant metastasis was observed. The tumor had perforated the abdominal wall and formed an abscess. Upon visiting our hospital, emergency surgery was performed. An abdominal wall incision was made to drain the abscess and laparoscopic colostomy was performed. Histopathological examination of biopsy specimens revealed an adenocarcinoma with positive immunohistochemical expressions of both CDX2 and CK20. The patient was diagnosed with a descending colon cancer. Genetic examination found MSI-high, Kras mutation (F12G), and wild-type BRAF. After the inflammation improved, chemotherapy with the FOLFIRI regimen was initiated, but the tumor grew rapidly. As a second-line treatment, nivolumab and ipilimumab combination therapy was initiated. After four cycles of these therapies, the patient was administered nivolumab alone for five cycles. Tumor shrinkage was observed and radical surgery was performed. The patient underwent laparoscopic descending colon and partial thoracic and abdominal wall resection. The abdominal wall muscle was dissected from the abdominal cavity, and subcutaneous tissues, diaphragm, ribs were dissected from the body surface. Pathological examination revealed mucus components, fibrous tissues, and no malignant cells, indicating a complete pathological response (pCR). The patient had a good postoperative course and returned to work after being discharged. No recurrence was observed six months postoperatively.

CONCLUSIONS

Herein, we report a case of anticancer drug-resistant MSI-high colon cancer that was resected after treatment with immune checkpoint inhibitors, and a pCR was achieved. This new treatment strategy can be used for the treatment of cases that are not responsive to conventional therapies.

摘要

背景

对于局部晚期结肠癌,若肿瘤广泛贴近或疑似侵犯骨骼肌、主要器官及血管,则需进行术前治疗。基于奥沙利铂的方案常用于术前化疗。然而,微卫星高度不稳定(MSI-H)的结直肠癌通常对细胞毒性抗癌药物耐药。在此,我们描述一例抗癌药耐药的MSI-H局部晚期结肠癌的治疗病例,并回顾结直肠癌对免疫检查点抑制剂治疗完全缓解的病例。

病例介绍

一名57岁女性因降结肠巨大肿瘤并累及胸腹壁(包括肋骨和膈肌)被转诊至我院。未观察到远处转移。肿瘤已穿透腹壁并形成脓肿。来我院就诊时,进行了急诊手术。做腹壁切口引流脓肿并实施了腹腔镜结肠造口术。活检标本的组织病理学检查显示为腺癌,CDX2和CK20免疫组化表达均为阳性。该患者被诊断为降结肠癌。基因检测发现为MSI-H、Kras突变(F12G)且BRAF为野生型。炎症改善后,开始采用FOLFIRI方案化疗,但肿瘤迅速生长。作为二线治疗,开始使用纳武单抗和伊匹单抗联合治疗。经过四个周期的这些治疗后,患者单独使用纳武单抗五个周期。观察到肿瘤缩小,遂进行了根治性手术。患者接受了腹腔镜下降结肠及部分胸腹壁切除术。从腹腔分离腹壁肌肉,从体表分离皮下组织、膈肌和肋骨。病理检查显示有黏液成分、纤维组织,未见恶性细胞,表明达到了完全病理缓解(pCR)。患者术后恢复良好,出院后重返工作岗位。术后六个月未观察到复发。

结论

在此,我们报告一例抗癌药耐药的MSI-H结肠癌病例,经免疫检查点抑制剂治疗后切除,并实现了pCR。这种新的治疗策略可用于治疗对传统疗法无反应的病例。

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