Virchow Lymph Node Metastatic Recurrence of Sigmoid Colon Cancer with Severe Lymph Node Metastases Successfully Treated Using Systemic Chemotherapy Combined with Radiotherapy

Case Report

The case is of a 58-year-old man who presented with the main complaint of defecation trouble, diarrhea and stool pillar narrowness. On physical examination, the performance status (PS) was 0, there was no abdominal pain, and an elastic hard mass was palpable in the left lower quadrant of the abdomen. Colonoscopy showed type 2 advanced colonic cancer in the sigmoidal colon. A barium enema study showed irregular stenosis of approximately 3 cm from the sigmoidal colon (Figure 1). Computed tomography (CT) showed hypertrophy in the sigmoidal wall with a heterogeneous contrast effect and fluffing in the surrounding adipose tissue. The border with the small intestine was indistinct, and permeation was suspected. A small nodular shadow was suspected as being lymph node metastases in the adipose tissue around the tumor. Swelling in the para-aortic lymph nodes in the area of the superior mesenteric artery bifurcation suggested lymph node metastases (Figure 2). No metastasis was seen in the liver and lungs. The preoperative carcinoembryonic antigen level was 0.8 ng/ml. The preoperative diagnosis was sigmoidal colonic cancer, cSI, cN3, cH0, cP0, cM1 (para-aortic lymph node) cStageIV in the Japanese Classification of Colorectal Carcinoma (JCCC) (1).

Treatment strategy. To treat the passage disorder, we resected the primary tumor with palliative intent, and resected the para-aortic lymph node for histological examination. R2 surgery was achieved (para-aortic lymph node remained). We administered bevacizumab at 7.5 mg/kg and oxaliplatin at 130 mg/m² on day 1 plus capecitabine at 1000 mg/m² twice daily on days 1-14, every three weeks from postoperative day 21 as systemic chemotherapy.

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Figure 1.

The barium enema study showed an irregular stenosis image of approximately 3 cm from the sigmoidal colon.

Pathological findings. The pathology results were poorly-differentiated adenocarcinoma, ly2, v2, lymph node metastasis: 3/17 (positive total), para aortic lymph node: 3/17 (positive total), pSS, pN1, cH0, pP0, pM1 (para aortic lymph node) fStage IV by JCCC (1) (Figure 2). Staining for epidermal growth factor receptor (EGFR) was positive on immunohistochemistry. V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) was wild type.

Episode of care. The patient received 11 cycles of capecitabine, oxaliplatin and bevacizumab therapy for para-aortic lymph node metastases. The best overall response was a partial response, and we then changed to FOLFIRI plus bevacizumab (bevacizumab at 5 mg/kg, irinotecan at 180 mg/m², folinic acid at 400 mg/m², fluorouracil (5-FU) bolus at 400 mg/m² on day 1 and 5-FU continuous intravenous infusion at 1200 mg/m² on days 1-2, every two weeks) due to onset of peripheral neuropathy grade 3. Peripheral neuropathy was improved by the four-cycle dosage of FOLFIRI plus bevacizumab to grade 1, and then we changed therapy to modified FOLFOX6 plus bevacizumab (bevacizumab at 5 mg/kg, oxaliplatin at 85 mg/m², intravenous infusion folinic acid at 400 mg/m², bolus 5-FU at 400 mg/m² on day 1 and continuous intravenous infusion of 5-FU at 1200 mg/m² on days 1-2, every two weeks) and FOLFIRI plus bevacizumab every four cycles (2). At 20 months postoperatively, metastasis in the left supraclavicular lymph node was detected on CT (Figure 4), on fluorodeoxyglucose positron-emission tomography (PET) (Figure 5), and on ultrasonograpy after 24 cycles in total. The abdominal para-aortic lymph node metastasis had disappeared. We started modified FOLFOX6 plus cetuximab [(250 mg/m²) on day 1, every week]. For the metastasis to the left supraclavicular lymph node, stable-disease status was achieved, and for other metastases, complete resposnse (CR) was achieved. However, we switched to tegafur, gimeracil, oteracil potassium (TS1) at 80 mg/day (two weeks administration, one week discontinuation) plus cetuximab at 250 mg/m² (weekly) because we noticed protraction in peripheral neuropathy grade 2 and fatigue grade 1. The side-effect was relieved, and compliance was improved. After eight cycles, the metastasis to the left supraclavicular lymph node had increased to approximately 5 cm, with tenderness macroscopically. Surgical treatment was difficult anatomically, and so radiotherapy was performed. At 22 months postoperatively, this site was irradiated with 15 times of 3 Gy a total 45 Gy. Other sites of metastasis were controlled, and systemic chemotherapy was resumed. The symptoms were relieved immediately after radiotherapy, and there was reduction in tumor size. The tumor was gradually reduced and had disappeared macroscopically by day 48 after radiotherapy. We continued TS1 plus cetuximab, and the metastasis of the left supraclavicular lymph node disappeared on CT (Figure 4). No other metastasis was seen. There was no accumulation on PET (Figure 5). CR was maintained by 12 cycles of TS1+cetuximab administration in total. Because dermatopathy, paronychia, fatigue and diarrhea grade 1 appeared, we switched to TS1 alone. However, he was not able to receive it because diarrhea continued. We are following-up with no treatment, and CR has continued for more than 10 months. Figure 6 shows the clinical course.

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Figure 2.

Pathological findings: Macroscopic findings (A) and microscopic findings of poorly differentiated adenocarcinoma (B, ×40; C, ×200).