Selection criteria for high risk and low risk groups of recurrence and metastasis in patients with primary colorectal cancer

Abstract.Lymph nodes from patients with colorectal cancer were immunohistochemically stained for cytokeratin to investigate the relationship between the presence of occult neoplastic cells (ONCs) and recurrence/metastasis. A total of 80 patients with stage III/Dukes' C colorectal cancer were divided into 16 patients who developed recurrence/metastasis (recurrence group) and 64 patients without recurrence (nonrecurrence group). ONCs were compared between the two groups with respect to i) single cells (≥3 floating ONCs), ii) clusters of cells (1 or more floating aggregates of 2-20 ONCs) and iii) single cells + clusters. When single cells were detected, the sensitivity for recurrence was 87.5% (14/16, p=0.002), the positive predictive value (PPV) was 32.6% (14/43), the specificity was 54.7% (35/64) and the negative predictive value (NPV) was 94.6% (35/37). For clusters, the sensitivity was 87.5% (14/16, p<0.001), PPV was 41.2% (14/34), specificity was 68.8% (44/64) and NPV 95.7% (44/46). With single cells + clusters, the values were 87.5% (14/16, p<0.001), 48.3% (14/29), 76.6% (49/64) and 96.1% (49/51), respectively. These results suggest that the detection of single cells + clusters is a sensitive indicator of a high risk of recurrence/metastasis, while ONCs are useful for identifying the low-risk group of patients with stage III colorectal cancer. IntroductionThe 5-year survival rate of Japanese patients who have stage II/ Dukes' B colorectal cancer without lymph node metastasis and receive curative resection is approximately 80% (colon, 84.5±2.8%; rectum, 79.8±4.0%), whereas the 5-year survival rate is considerably lower at approximately 60% (colon, 74.0±3.5%; rectum, 64.7±4.3%) for patients with stage III/ Dukes' C colorectal cancer and lymph node metastasis who undergo curative resection (1-4). Thus, recurrence/metastasis develops in 30-40% of stage III/Dukes' C patients after curative resection and can be fatal (2,4). According to the pathological concept of breast cancer, positive lymph node metastasis indicates systemic disease with the potential for metastasis to other organs and the presence or absence of lymph node metastasis is considered to be one of the most important clinical markers (5,6). Hematogenous metastasis to the liver or the lungs in patients with lymph node metastasis who undergo curative resection is presumed to occur when cancer cells circulating in the blood during the perioperative period, escape the immune system enter the microcirculation of the liver or the lungs, and find appropriate microenvironment for growth and proliferation (7-10). Various reports have been published about the close relationship between recurrence/metastasis of cancer and detection of occult neoplastic cells (ONCs) positive for cytokeratin immunohistochemical staining and floating in the sinuses of lymph nodes distant from the primary tumors (11-15). ONCs can be semiquantified by a relatively simple immunostaining method and represent floating tumor cells target trapped in the microcirculation of the lymph node...

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Occult neoplastic cells in the lymph node sinuses and recurrence/metastasis of stage III/Dukes' C colorectal cancer

Sekido

Mukai²,

Kishima³

et al. 2011

“…Unlike other gastrointestinal malignancies, including gastric cancer, surgery is still indicated for colorectal cancer even when it has metastasized to distant organs such as the liver and lungs (6,7). It is also known that colorectal cancer may cause fatal metastasis/recurrence in the liver or lungs after curative resection of the primary tumor, probably because free cancer cells circulate during the perioperative period and survive to proliferate in a distant organ after escaping from the immune system (8)(9)(10)(11). Many investigators have reported that cytokeratin-positive occult neoplastic cells (ONCs), which represent circulating cancer cells, in lymph node sinuses distant from the primary tumor are closely related to the distant metastasis/recurrence of cancer (12)(13)(14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

“…Many investigators have reported that cytokeratin-positive occult neoplastic cells (ONCs), which represent circulating cancer cells, in lymph node sinuses distant from the primary tumor are closely related to the distant metastasis/recurrence of cancer (12)(13)(14)(15)(16)(17)(18)(19). ONCs can be counted by immunostaining and represent floating malignant cells that have been trapped by the lymph nodes (8)(9)(10)(11). ONC clusters (<10 cells) formed by a number of floating ONCs or malignant micro-aggregates (≥10 cells) can induce the metastasis/recurrence of cancer in distant organs after being released from the primary tumor.…”

Section: Introductionmentioning

confidence: 99%

Alternating hepatic arterial infusion and systemic chemotherapy for stage IV colorectal cancer with synchronous liver metastasis

Mukai

Oida²,

Tajima³

et al. 2006

Self Cite

Abstract. Among 41 patients with synchronous liver metastases of colorectal cancer, 15 patients underwent synchronous resection of their liver metastases and achieved a median survival time (MST) of 1,441 days (versus 748 days for the 26 patients without resection, p=0.038), a median relapse-free survival time of 652 days (MST not reached), and a recurrence rate in the residual liver of 20% (3/15 patients). The alternating hepatic arterial infusion and systemic chemotherapy showed partial response (PR) in 6 cases, stable disease (SD) in 8 cases, and progressive disease (PD) in 1 case (n=15/26). They had an objective response rate of 40% (6/15), tumor control rate (≥ SD) of 93.3% (14/15), one-year progression-free survival rate of 35.7%, 50% time to progression of 270 days, one-year survival rate of 76.2%, and two-year survival rate of 50.8% (MST not reached). Grade 3 leucopenia was observed in 2/15 patients (13.3%). These results suggest that the present alternating therapy may become a standard regimen for patients in whom synchronous resection of liver metastases is impossible and patients who have stage IV colorectal cancer with a risk of recurrence in the remnant liver and/or at extrahepatic sites such as the lungs.

“…The residual cancer cells find a microenvironment in the liver, lungs, and/or peritoneum that is suitable for adhesion, and then proliferate at this site (6). In particular, there have been many studies on the close relationship to tumor metastasis/recurrence of occult neoplastic cells (ONCs), which are positive for cytokeratin on immunostaining and are found floating in lymph node sinuses distant from the primary tumor (7)(8)(9)(10). ONCs are a very small number of malignant cells that can be semiquantitatively assessed by immunostaining and are trapped in the lymph nodes, which are an important part of the body's immune/defense system (7,8).…”

Section: Introductionmentioning

confidence: 99%

Clinical comparison of QOL and adverse events during postoperative adjuvant chemotherapy in outpatients with node-positive colorectal cancer or gastric cancer

Mukai

Kishima²,

Uchiumi³

et al. 2009

Abstract. The aim of this study was to evaluate the quality of life (QOL) from the performance status (PS) and face scale (FS), and to compare adverse events (AEs) during chemotherapy in 28 patients with node-positive colorectal cancer (NP-CRC) and 15 patients with node-positive gastric cancer (NP-GC). The anticancer regimen consisted of 5-FU/ LV+CPT-11 for NP-CRC and 5-FU+low-dose CDDP for NP-GC. Results were evaluated after completion of three courses. QOL evaluation revealed no significant differences between the two groups with respect to PS and FS. Among hematological AEs, grade 1/2 mild leucopenia was significantly more common in NP-CRC than NP-GC patients (p<0.05), while grade 1/2 mild thrombocytopenia was significantly more common in NP-GC than NP-CRC patients (p<0.05). Among non-hematological AEs, grade 1/2 mild neuropathy (olfactory nerve) was significantly more common in NP-CRC than NP-GC patients (p<0.05). The monthly cost for one course was ~€586.8 for NP-CRC patients and ~€181.8 for NP-GC patients. These results suggest that first-line postoperative outpatient adjuvant chemotherapy for NP-CRC and NP-GC shows no significant differences with respect to QOL, but both AEs and the cost are higher for NP-CRC than for NP-GC.