ダイチョウ ガン ノ adenoma-carcinoma sequence ニ オケル EZH2 ハツゲン ノ ヘンカ

博士(医学）熊本大

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

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

Extracellular water to total body water ratio, a novel predictor of recurrence in patients with colorectal cancer

Abstract Background Total body water (TBW) fraction, which accounts for 60% of body weight, is an important indicator of body composition, and the extracellular water to TBW ratio (ECW/TBW) is reportedly useful in predicting clinical outcomes of patients with organ disorders. We aimed to clarify the clinical impact of preoperative ECW/TBW status on survival outcomes in cancer patients. Methods We used a database of 320 colorectal cancer (CRC) patients who underwent potentially curative resections. Preoperative ECW/TBW was measured using a bioelectrical impedance analysis (BIA), and its correlation with patient survival outcomes, clinicopathological factors, laboratory data, and comorbidities were analyzed. Results A high preoperative ECW/TBW was significantly associated with poorer relapse‐free survival (RFS; p = 0.001) and overall survival (OS; p = 0.003). A high ECW/TBW ratio was significantly associated with older age (p < 0.001), low BMI (p = 0.009), and right‐sided tumors (p = 0.03). In a multivariate analysis, a high ECW/TBW significantly predicted a higher RFS mortality (HR: 2.07, 95% CI: 1.10–3.88, p = 0.024) and OS mortality (HR: 3.23, 95% CI: 1.25–8.36, p = 0.016). Furthermore, a high ECW/TBW was significantly associated with lower hemoglobin (p < 0.001) and albumin levels (p < 0.001), but not comorbidities. Conclusions A high preoperative ECW/TBW was a predictive factor for recurrence and poorer overall survival independent of the tumor, node, and metastasis (TNM) stage. Our data suggest that preoperative evaluation of ECW/TBW using BIA might serve as a novel tool for developing CRC treatment strategies

Negative Impact of Skeletal Muscle Loss after Systemic Chemotherapy in Patients with Unresectable Colorectal Cancer.

Skeletal muscle depletion (sarcopenia) is closely associated with limited physical ability and high mortality. This study evaluated the prognostic significance of skeletal muscle status before and after chemotherapy in patients with unresectable colorectal cancer (CRC).We conducted a retrospective analysis of 215 consecutive patients with unresectable CRC who underwent systemic chemotherapy. Skeletal muscle cross-sectional area was measured by computed tomography. We evaluated the prognostic value of skeletal muscle mass before chemotherapy and the rate of skeletal muscle change in cross-sectional area after chemotherapy.One-hundred-eighty-two patients met our inclusion criteria. There were no significant differences in progression-free survival (PFS) or overall survival (OS) associated with skeletal muscle mass before chemotherapy. However, 22 patients with skeletal muscle loss (>5%) after chemotherapy showed significantly shorter PFS and OS compared with those without skeletal muscle loss (PFS, log-rank p = 0.029; OS, log-rank p = 0.009). Multivariate Cox regression analysis revealed that skeletal muscle loss after chemotherapy (hazard ratio, 2.079; 95% confidence interval, 1.194-3.619; p = 0.010) was independently associated with OS.Skeletal muscle loss after chemotherapy was an independent, negative prognostic factor in unresectable CRC

Skeletal muscle index and clinical and tumour features in patients with unresectable colorectal cancer.

<p>Abbreviations: CEA, carcinoembryonic antigen; EGFR, epidermal growth factor receptor.</p><p>Values given as mean ± standard deviation or number (%).</p><p>Skeletal muscle index and clinical and tumour features in patients with unresectable colorectal cancer.</p

Kaplan–Meier curves of progression-free survival (A) and overall survival (B) in patients with unresectable colorectal cancer according to quartiles (Q1–Q4) based on skeletal muscle index before chemotherapy.

<p>Kaplan–Meier curves of progression-free survival (A) and overall survival (B) in patients with unresectable colorectal cancer according to quartiles (Q1–Q4) based on skeletal muscle index before chemotherapy.</p

Association between rate of skeletal muscle loss and mortality in patients with colorectal cancer.

<p>Abbreviations: HR, hazard ratio; CI, confidence interval.</p><p>Association between rate of skeletal muscle loss and mortality in patients with colorectal cancer.</p

Univariate and multivariate analyses of factors associated with overall survival in patients with skeletal muscle analysis.

<p>Abbreviations: CEA: carcinoembryonic antigen; HR, hazard ratio; CI, confidence interval.</p><p>Univariate and multivariate analyses of factors associated with overall survival in patients with skeletal muscle analysis.</p

Characteristics of patients with initially unresectable colorectal cancer with or without skeletal muscle loss (>5%) during chemotherapy.

<p>Abbreviations: CEA, carcinoembryonic antigen; EGFR, epidermal growth factor receptor.</p><p>*16 patients did not require 2nd line chemotherapy and 5 patients had missing information.</p><p>^†22 patients did not require 3rd line chemotherapy and 7 patients had missing information.</p><p>Values given as median value (range) for age and BMI, or number (%).</p><p>Characteristics of patients with initially unresectable colorectal cancer with or without skeletal muscle loss (>5%) during chemotherapy.</p