Comparative Outcomes Between Initially Unresectable and Recurrent Cases of Advanced Pancreatic Cancer Following Palliative Chemotherapy
Peng XueMasashi KanaiYukiko MoriTakafumi NishimuraNorimitsu UzaYuzo KodamaYoshiya KawaguchiKyoichi TakaoriShigemi MatsumotoShinji ÜemotoTsutomu Chiba
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Objectives The objective of this study was to compare the clinical outcomes between initially unresectable and recurrent advanced pancreatic cancer (APC) patients after palliative chemotherapy. Methods Data of a total of consecutive 269 patients with pathologically confirmed APC patients who received palliative chemotherapy between January 2006 and April 2012 were reviewed. Patients were classified into initially unresectable and recurrent group, and overall survival (OS) was compared between the 2 groups. Results The median OS was significantly longer in the recurrent group compared with the initially unresectable group (383 vs 308 days; hazard ratio [HR], 0.59; 95% confidence interval, 0.44–0.80; P < 0.01). After adjustment for distant metastasis, performance status, and levels of carbohydrate antigen 19-9, carcinoembryonic antigen, C-reactive protein, and lactate dehydrogenase, the status of recurrent or unresectable disease remained as an independent prognostic factor with a clinically relevant HR value (HR, 0.66; 95% confidence interval, 0.48–0.90; P = 0.01). In addition, the 2-year OS rate of the recurrent group was significantly higher than that of the unresectable group (24.2% vs 9.6%, P = 0.01). Conclusions Our results suggested that the status of recurrent or initially unresectable disease was an independent prognostic factor in APC patients receiving palliative chemotherapy.Keywords:
Carcinoembryonic antigen
Palliative chemotherapy
Carcinoembryonic antigen has been used to monitor colorectal cancer treated patients, elevated carcinoembryonic antigen allows to predict recurrence however some serum levels is not ever a sign of disease. In a last paper 21% of the colorectal cancer patients treated surgically had not recurrent disease. The aim of the study was to follow these patients for at least one year. Thirty two patients with elevated carcinoembryonic antigen serum levels were studied. Five were excluded and 27 were followed with chest RX, computadorized tomography and colonoscopy. Carcinoembryonic antigen serum levels were measured by ELISA using Sorine Biomedica kit (normal value: 5 ng/ml). Eleven patients (41%) developed recurrence, seven had liver metastasis. The mean time among the elevated serum carcinoembryonic antigen and the recurrence was 6.6 months. The recurrence was not observed in 18 patients, the carcinoembryonic antigen serum levels become normal in eight and in the eight others the carcinoembryonic antigen serum levels persisted elevated. Carcinoembryonic antigen serum levels can be elevated before the diagnosis of recurrence, mostly in liver metastasis, however, a number of patients with elevated carcinoembryonic antigen serum levels do not have a known cause.
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Carcinoembryonic antigen rarely exceeds serum levels of 10-12 ng/mL in benign diseases and has never been found above 24 ng/ml. We report a case in which carcinoembryonic antigen serum levels reached the value of 44.9 ng/ml without any overt reason (after 22 months of follow-up). A decline of the carcinoembryonic antigen to normal ranges was noticed after a radiolabeled anti-carcinoembryonic antigen monoclonal antibody scan was performed. The reason for this phenomenon is unclear.
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Serum carcinoembryonic antigen is used mainly for tumor follow-up to detect recurrence of colonic cancer. However, raised preoperative carcinoembryonic antigen levels may be helpful for the identification of understaged cases and of patients meriting more intensive preoperative and postoperative diagnostic workup.From a prospectively collected database, the data on 261 patients who had curative colonic carcinoma with a minimal follow-up of five years and who had preoperative carcinoembryonic antigen levels assessed were retrieved and analyzed. Outcome parameters were local and/or distant recurrence and time to recurrence. These parameters were correlated with Dukes staging and preoperative carcinoembryonic antigen levels.The cumulative disease-free survival of patients with a preoperative carcinoembryonic antigen level within the normal range was significantly better than that of those whose carcinoembryonic antigen was 5 ng/ml or more (P = 0.001). No patient with carcinoembryonic antigen levels less than 1 ng/ml developed metastatic recurrence. Twenty-three percent of all patients with a raised carcinoembryonic antigen above 5 ng/ml compared with 2.1 percent of patients with carcinoembryonic antigen below 5 ng/ml developed a metastasis at two years. At five years, these figures were 37.2 percent and 7.5 percent, respectively. Dukes staging and carcinoembryonic antigen levels were found to be directly correlated (P < 0.001) when all patients were included. Carcinoembryonic antigen of more of 15 ng/ml was found to be a significant adverse prognostic indicator for disease-free survival irrespective of Dukes staging (P < 0.02). Raised carcinoembryonic antigen levels predicted distant metastatic recurrence (P < 0.001) but did not predict local recurrence (P = 0.72).High preoperative carcinoembryonic antigen levels above 15 ng/ml predicted an increased risk of metastatic recurrence in potentially curative colonic cancer and may indicate undetectable disseminated disease. Preoperative carcinoembryonic antigen levels predict understaging and the possibility of distant recurrence. Such patients may therefore be selected for adjuvant therapy where indicated. Therefore, carcinoembryonic antigen is complementary to conventional Dukes staging for the prediction of recurrence and survival.
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We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups. miR-29c suppresses cell migration and invasion by targeting the MMP2 3′UTR. Overexpression of miR-29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic implantation model. miR-29c expression was associated with metastasis and pancreatic cancer patient survival. miR-29c plays an important role in mediating pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c may serve as a novel marker of pancreatic cancer metastasis and possibly as a therapeutic target to treat pancreatic cancer liver metastasis.
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Since it has been suggested that colonic obstruction due to carcinoma may play a role in elevations of circulating carcinoembryonic antigen, serial plasma carcinoembryonic antigen levels were studies in 19 patients with intestinal obstruction due to tumor and nontumor causes. Regardless of cause, eight of ten patients with colonic obstruction did not show decreased carcinoembryonic antigen levels after decompression. Two patients with postoperative carcinoembryonic antigen reductions of greater than 40 per cent had ascite removed at operation. Removal of a large volume of carcinoembryonic antigen-rich ascites was thought to contribute to the fall in circulating carcinoembryonic antigen. Six patients with small intestinal obstruction and one patient with large and small intestinal obstruction did not show a reduction in postdecompression carcinoembryonic antigen levels. One patient with Crohn's disease who underwent ileal resection and one with intestinal obstruction due to carcinoma of the ovary who underwent resection at the time of decompression had a greater than 40 per cent reduction in postoperative carcinoembryonic antigen levels. Inflamed intestinal and carcinoma of the ovary are known sources of carcinoembryonic antigen and their removal could explain the decrease in carcinoembryonic antigen. Rehydration, as monitored by plasma osmolality and protein concentration, did not explain changes in plasma carcinoembryonic antigen. Thus, it appears that carcinoembryonic antigen production may play a more significant role in the regulation of circulating carcinoembryonic antigen than the physiopathologic processes associated with obstruction.
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The aim of this study was to evaluate the serum carcinoembryonic antigen levels in the diagnosis and in monitoring colorectal cancer patients at different Dukes' stage. Carcinoembryonic antigen serum levels were measured by Elisa using Sorine Biomedica kit (normal value: 5 ng/ml) in 240 colorectal adenocarcinoma. In the diagnosis, carcinoembryonic antigen levels were measured in 109 patients, in 42% of them, the carcinoembryonic antigen levels were elevated. The carcinoembryonic antigen levels were also evaluated in 309 serum from treated colorectal cancer patients. Fifty-nine percent of the serum of the patients with recurrence disease had elevated carcinoembryonic antigen levels and 41% of the serum of patients without recurrence also have elevated serum carcinoembryonic antigen levels. Ninety percent of the serum from treated patients without recurrence have normal serum carcinoembryonic antigen levels. We concluded that the sensitivity of carcinoembryonic antigen is lower in the diagnosis as described in others studies, mostly in patients with better prognosis. In the monitoring, patients with normal serum carcinoembryonic antigen levels, probably have no recurrence of the disease. In the other hand, patients with elevated serum carcinoembryonic antigen levels can have or not relapsed disease.
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The CEA-plasma level was determined in 10 patients with malignant obstruction of the large intestine and in 6 patients with benign obstruction of the small intestine. The plasma carcinoembryonic antigen levels were obtained prior to initiating of the treatment and sequentially after treating the complete obstruction. Elevated plasma carcinoembryonic antigen levels are related to the carcinoembryonic antigen production by the primary tumour and not additionally to the obstruction. An elevated plasma CEA level in patients with benign obstruction could not be detected. After relief of obstruction, significant changes in the mean carcinoembryonic antigen values could not be observed.
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Our patients have demonstrated that serial carcinoembryonic antigen determinations contributed to the detection of recurrent tumor and that shortening the delay between carcinoembryonic antigen elevation and reoperation has resulted in an increase from 27 to 78 per cent in instances of resectable recurrent tumor encountered. If these results continue to be substantiated, the carcinoembryonic antigen assay has made a significant contribution in the control of this disease. Serial carcinoembryonic antigen assays should be performed every two months. All benign inflammatory conditions that cause carcinoembryonic antigen elevations must be searched for, and ruled out, before reoperation is decided upon. The physician must be cognizant not only of the significance of the assay but also of the limitations, and he must rely heavily on his clinical judgment.
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A radioimmunoassay for carcinoembryonic antigen with utilization of the so-called sandwich method was established and used for clinical investigation. A collaborative study was made through the cooperation of 34 institutions in Japan, and serum samples from about 400 normal adults, 500 patients with benign diseases, and 1500 cancer patients were assayed. About 90% of the normal adults showed carcinoembryonic antigen levels of under 2.5 ng/ml. The benign disease group showed somewhat higher levels than did the normal group, and the cancer group had levels significantly higher than those of the benign group. The levels were strikingly high in cases of advanced cancer with metastases. The specificity of carcinoembryonic antigen and its antiserum is discussed.
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