A small rise in CEA is sensitive for recurrence after surgery for colorectal cancer

OBJECTIVE: Rise in carcinoembryonic antigen (CEA) above normal limits can indicate recurrent colorectal cancer. The aim of this study was to evaluate whether a small rise in CEA, even within normal limits was a sensitive indicator of recurrence. METHOD: 150 patients aged 22-87 years were followed up for a mean of 27 months after colorectal surgery with CEA 3 and 6 monthly computerized tomography. We analysed whether a rise in CEA > 1 ng/ml correlated with recurrence of metastases. RESULTS: Forty-six of 139 patients in final analysis had recurrent disease. A rise in CEA > 1 had a predictive value of 74% for recurrence or metastases (sensitivity 80%, specificity 86%). These findings were similar whether or not the CEA was normal preoperatively. CONCLUSION: If CEA is measured after surgery for colorectal cancer, a rise of >1 in the patient's postoperative value is predictive for recurrence or metastases with an overall sensitivity of 80% and specificity of 86%. Previous studies have recognized the role of large rises in CEA in predicting recurrence but this study shows that small changes in CEA may be significant even if these levels would be traditionally within 'normal' limits.     

Is carcino-embryonic antigen useful in the follow-up management of patients with colorectal liver metastases?

BACKGROUND: The role of carcino-embryonic antigen (CEA) in monitoring early detection of recurrent or metastatic colorectal cancer, and its impact on resectability rate and patient survival remains controversial. Our objective was to determine any association between the preoperative level of CEA and prognosis, and the resectability and survival by method of diagnosis of colorectal hepatic metastases. METHODS: We analyzed patients who underwent exploration for hepatic resection for metastatic colorectal cancer over a 15-year period. The patient population consisted of those patients who had undergone primary colon or rectal resection and were followed up with serial CEA levels and of patients who were followed up with physical examination, liver function tests (LFTs) or computed tomography (CT) of the abdomen and pelvis that led to the diagnosis of liver metastases. Also included in the study were patients who were diagnosed with liver metastases at the time of the primary colon or rectal resection and underwent planned hepatic resection at a later time. RESULTS: Three hundred and one (301) patients who underwent a total of 345 planned hepatic resections for metastatic colorectal cancer between January 1978 and December 1993 were included in this analysis. The median preoperative CEA level was 24.8 ng/mL in the resected group, 53.0 ng/mL in the incomplete resection group, and 49.1 ng/mL in the nonresected group (P = 0.02). More of the patients who had a preoperative CEA < or =30 ng/mL were in the resected group, while those who had a preoperative CEA >30 ng/mL were likely to be in the nonresected group (P = 0.002). The median survival was 25 months for patients with a preoperative CEA level < or =30 ng/mL and 17 months for patients with a preoperative CEA >30 ng/mL (P = 0.0005). The resectability rate and the survival of patients by method of diagnosing liver metastases-rising CEA versus history and physical, elevated LFTs, CT scan versus diagnosis at the time of primary resection-was not significant (P = 0.06 and P = 0.19, respectively). Given the nonstandardized retrospective nature of the study cohort and relative small groups of patients, the power to detect small differences in survival by method of diagnosis is limited. In the complete resection group of patients with unilobar liver disease (5-year survival of 28.8%) there was no difference in survival between those patients who had normal preoperative CEA and those who had elevated preoperative CEA, and approximately 90% of them had an abnormal preoperative serum CEA level. CONCLUSIONS: CEA is useful in the preoperative evaluation of patients with hepatic colorectal metastases for assessing prognosis and is complimentary to history and physical examination in the diagnosis of liver metastases. Patients with colorectal liver metastases and preoperative CEA < or =30 ng/mL are more likely to be resectable, and they have the longest survival.     

GASTROINTESTINAL CANCER FOLLOW-UP: THE EFFECTIVENESS OF SEQUENTIAL CEA,TPA AND CA 19–9 EVALUATION IN THE EARLY DIAGNOSIS OF RECURRENCES

One-hundred and seventy-four consecutive patients who underwent curative resection for gastric and colorec-tal cancer between 1983 and 1985 were studied prospectively to evaluate the roles of sequential carcino-embryonic antigen (CEA), tissue polypeptide antigen (TPA) and Ca 19–9 determinations and independent clinical examinations, in the early diagnosis of resectable recurrences. Sixty-six recurrences (33 from gastric and 33 from colorectal cancer) were detected between 6 and 42 months after primary surgery. In gastric cancer CEA, TPA and Ca 19–9 showed a sensitivity of 64%. 73% and 60% respectively and a specificity of 67%. 65% and 54% respectively. Nine patients (27%) underwent surgical treatment for recurrent disease, and four of these (44.4%) had resectable recurrence, for a total resectability rate of 12%. Of these four patients, three are still living after 12, 36 and 44 months respectively from re-operation without evidence of neoplastic disease. In one of these patients, re-operation was performed on the basis of the elevation of the three markers, without any other clinical sign of disease. This patient had a resectable solitary hepatic recurrence. In colorectal cancer, CEA, TPA and Ca 19–9 showed a sensitivity of 73%. 73% and 49% respectively, and a specificity of 77%. 87% and 97% respectively. Fourteen patients (42.4%) underwent surgical treatment for recurrent disease and eight of these (57%) showed resectable recurrence, for a total resectability rate of 24.2%. Six patients are still living after 9, 16, 21, 31, 41 and 53 months respectively from re-operation without evidence of neoplastic disease. In four cases the rises of the three marker levels was the one sign of recurrent disease. In one case, the operation revealed a peritoneal carcinomatosis, and in the other three cases resectable hepatic metastases were found. All these three patients are still living and disease-free. In 46 cases, the rise in the value of CEA (35 cases) and/or TPA (34 cases) and/or Ca 19–9 (28 cases) was the first sign of recurrence. and the diagnosis was established later by clinical methods. In this group. the median time for diagnosis of recurrence, based on increase in initial markers comparison with routine clinical and instrumental follow-up (lead time), was 3 months for liver metastases and 4 months for disseminated metastases. The results of our study indicate that a follow-up programme based on CEA, TPA and Ca 19–9 assays is related to an early diagnosis and good resectability rate for recurrent gastric disease.     

The usefulness of CEA as an indicator for early detection and a guide to the treatment of recurrent gastric cancer

The usefulness of carcinoembryonic antigen (CEA) as an indicator for recurrence and a guide to the treatment was evaluated from a retrospective analysis of 88 patients with recurrent gastric cancer. Sixty-two of these patients (70.5 per cent), 25 of whom had a preoperative positive assay, and 37 a negative assay, had elevated levels of CEA after disease progression. Averaged CEA level in patients with liver metastasis was significantly higher (872 ng/ml) than in those with peritoneal metastasis (68 ng/ml), with lymph node metastasis (103 ng/ml) or with local metastasis (93 ng/ml) (p less than 0.01). An elevation of CEA was found prior to the clinical manifestation of recurrence, and the average lead time was 4 months. In 25 patients with a lead time of more than 4 months, survival time after CEA elevation was 13.3 months, which was longer than the 6.5 months of 28 patients with less than 4 months. Thirty-seven of the 88 patients were treated after recurrence. The average survival period after the detection of recurrence was 9.4 months in patients with surgical treatments followed by chemotherapy, 5.9 months in those with chemotherapy alone and 3.8 months in those with surgery alone. The average survival period of 26 patients with positive CEA assays in recurrence was 5.1 months longer than of patients with negative assays. This fact suggested that early detection of recurrence followed by various treatments, in the elevated CEA group, contributes to favorable results.     

The usefulness of CEA as an indicator for early detection and a guide to the treatment of recurrent gastric cancer

The usefulness of carcinoembryonic antigen (CEA) as an indicator for recurrence and a guide to the treatment was evaluated from a retrospective analysis of 88 patients with recurrent gastric cancer. Sixty-two of these patients (70.5 per cent), 25 of whom had a preoperative positive assay, and 37 a negative assay, had elevated levels of CEA after disease progression. Averaged CEA level in patients with liver metastasis was significantly higher (872 ng/ml) than in those with peritoneal metastasis (68 ng/ml), with lymph node metastasis (103 ng/ml) or with local metastasis (93 ng/ml) (p<0.01). An elevation of CEA was found prior to the clinical manifestation of recurrence, and the average lead time was 4 months. In 25 patients with a lead time of more than 4 months, survival time after CEA elevation was 13.3 months, which was longer than the 6.5 months of 28 patients with less than 4 months. Thirty-seven of the 88 patients were treated after recurrence. The average survival period after the detection of recurrence was 9.4 months in patients with surgical treatments followed by chemotherapy, 5.9 months in those with chemotherapy alone and 3.8 months in those with surgery alone. The average survival period of 26 patients with positive CEA assays in recurrence was 5.1 months longer than of patients with negative assays. This fact suggested that early detection of recurrence followed by various treatments, in the elevated CEA group, contributes to favorable results.     

Use of CEA as an Indicator of Early Recurrence and as a Guide to a Selected Second-look Procedure in Patients with Colorectal Cancer

The usefulness of the CEA as an indicator of recurrence and a guide to selected second-look surgery was evaluated from a retrospective analysis of 358 patients with colorectal cancer and from a prospective experience with 16 patients all of whom had been admitted for second-look surgery because of postoperative elevations of CEA only. Our previous experience had shown that after curative resection the CEA usually returned to normal levels (less than 5 ng/ml) within one month, but became elevated at time of clinically obvious recurrence being very high in patients with liver metastases, but only moderately elevated or normal in patients with local recurrence. All 16 patients had previously had curative resection of colorectal cancer; 13 in the rectum or rectosigmoid and three in the right colon. There were 13 Dukes' C and three Dukes' B cancers. All had been followed clinically and by CEA testing at three monthly intervals and were considered free of disease (NED) at time of CEA elevation.

The median disease free interval was 13 months (range 4-57 months) and the median CEA prompting admission for second-look operation was 21 ng/ml (range 10-56 ng/ml). The sites of recurrence were liver in six, lung in two and localized disease in six. Two patients had negative exploration for recurrence and were found to have cholelithiasis only (one of these later died of metastases). Resection for cure was done in seven and palliative resection or biopsy only was done in nine patients. At this time, four patients are NED (12-37 months), five are living with disease (10-16 months) and seven have died of disease (2-12 months). The CEA test provides a method of early detection of recurrence and may permit surgical retrieval in selected patients and earlier initiation of palliation in other patients. The longterm effects in patient salvage remain to be defined.

     

Prognostic value of carcinoembryonic antigen and CYFRA21-1 in patients with pathological stage I non-small cell lung cancer.

BACKGROUND: The aim of this retrospective study was to assess the prognostic value of serum tumor markers (carcinoembryonic antigen (CEA) and CYFRA21-1) in patients with pathologic (p-) stage I non-small cell lung cancer (NSCLC) undergoing complete resection. METHODS: Two hundred and seventy-five patients (163 males, 112 females, mean age 67.1 years) with p-stage I NSCLC who underwent complete resection at our institution between April 1999 and October 2004 were examined. Patients who had received preoperative chemotherapy or radiotherapy were excluded, as were patients who had multiple malignancies including multiple lung cancer. The serum levels of tumor markers were measured using commercially available immunoassays within 1 month before surgical resection. Serum levels of CEA and CYFRA21-1 higher than 5.0 and 2.8 ng/ml, respectively, were considered as positive according to the manufacture's instructions. RESULTS: The histological classification was adenocarcinoma in 193 patients, squamous cell carcinoma in 71, large cell carcinoma in 5, and other histological type in 6. One hundred and fifty-seven patients had T1 disease and 118 patients had T2 disease. The positive ratio of CEA and CYFRA21-1 was 25.7% and 13.7%, respectively, and in relation to histological type was 27.8% and 7.8% in adenocarcinoma, and 20.6% and 28.4% in squamous cell carcinoma. The overall 5-year survival rate was 79.3%. With a median follow-up of 35.5 month for surviving patients, those with initial CYFRA21-1 serum levels higher than 2.8 ng/ml had a significantly worse prognosis (p=0.0041). Patients with an elevated preoperative CEA level exceeding 5.0 ng/ml had a shorter disease-free survival period (p=0.0003). In patients with adenocarcinoma, a CEA level above 5.0 ng/ml was associated with shorter survival and early recurrence, whereas CYFRA21-1 showed no such association. In patients with squamous cell carcinoma, elevated preoperative CEA was not related to survival and recurrence. In these patients, preoperative CYFRA21-1 level exceeding 2.8 ng/ml was associated with a poorer outcome, whereas preoperative CYFRA21-1 level was not associated with cancer recurrence. CONCLUSION: The patients with p-stage I adenocarcinoma whose preoperative CEA level was high might be considered as good candidates for adjuvant chemotherapy. The prognostic value of CYFRA21-1 could not be confirmed for stage I NSCLC, and preoperative CYFRA21-1 level was not useful in selecting the candidates for adjuvant chemotherapy.     

Pelvic resection of recurrent rectal cancer.

OBJECTIVE: The authors describe their experience with pelvic resection of recurrent rectal cancer with emphasis on patient selection for curative intent based on known tumor risk factors. SUMMARY BACKGROUND DATA: Pelvic recurrence is a formidable problem in 30% of patients who have undergone a curative resection of primary rectal cancer. Although radiation can reduce the development of local recurrence and can provide palliation to many patients with localized disease, it is not curative. The authors and others have used the technique of abdominal sacral resection (ABSR) with or without pelvic exenteration to resect pelvic recurrence and its musculoskeletal extensions in selected patients with satisfactory long-term survival. METHODS: The technique of ABSR with or without pelvic exenteration or resection of pelvic viscera, which the authors have described previously, was used in 53 patients with recurrent rectal cancer--47 patients for curative intent and 6 for palliation. Previous surgeries were abdominal perineal resections (APRs) in 26 patients, anterior resections in 19 patients, and other procedures in 2 patients; original primary Dukes' stage was B in 52% and C in 48%. Almost all patients had been irradiated previously, generally in the 4000 to 5900 cGy range. Preoperative carcinoembryonic antigen (CEA) levels (before ABSR) were elevated (> 5 ng/mL) in 54%. RESULTS: Postoperative morbidity was encountered in most patients. Mortality was 8.5% in the curative group. Long-term survival for 4 years was achieved in 14 of 43 patients (33%), and 10 patients were alive with an acceptable quality of life after 5 years. Patients who had previous anterior resections or whose preoperative CEA levels were less than 10 ng/mL had a survival rate of approximately 45%, whereas patients with previous APRs and preoperative CEA levels greater than 10 ng/mL had a survival rate of only 15% to 18%. Patients with bone marrow invasion, positive margins, or pelvic node metastases had a median survival of only 10 months. CONCLUSIONS: Pelvic recurrence of rectal cancer can be resected safely with expectation of long-term survival of 33%. Patient selection based on known risk factors can identify patients most likely to benefit from resection and eliminate those who should be treated for palliation only.     

Carcinoembryonic antigen testing after curative liver resection for synchronous liver metastasis of colorectal cancer: a Japanese multicenter analysis

Purpose

To identify the possible roles of carcinoembryonic antigen (CEA) testing after liver resection for synchronous colorectal liver metastasis (CLM).

Methods

The subjects of this retrospective study were patients who underwent complete resection of primary tumors and synchronous CLM between 1997 and 2007 at 20 institutions in Japan. We studied the associations between perioperative CEA levels and the characteristics of recurrence.

Results

Recurrence was detected during the median follow-up time of 52 months in 445 (73.7%) of the total 604 patients analyzed. A postoperative CEA level >5 ng/ml was an independent predictor, with the highest hazard ratio (2.25, 95% confidence interval 1.29–3.91, P = 0.004). A postoperative CEA level >5 ng/ml had a specificity of 86.2% and a positive predictive value of 84.2% for recurrence. Patients with a high postoperative CEA level had a significantly higher recurrence rate, with a shorter time until recurrence and a higher frequency of multiple metastatic sites than those with a low postoperative CEA level. Among the patients with recurrence, 173 (52.7%) had an elevated CEA level (>5 ng/ml) when recurrence was detected.

Conclusions

A postoperative CEA level >5 ng/ml was an independent predictor of recurrence; however, CEA testing was not a reliable surveillance tool to identity recurrence after liver resection.

     

Patients with high risk of hematogenous metastasis and recurrence in colorectal cancer: correlation with histopathologic variables and tumor markers, CEA and CA19-9, in peripheral and draining venous blood

Correlations of hematogenous metastasis with histopathologic variables, preoperative CEA and CA19-9 levels in peripheral (p) venous blood, and those in draining (d) venous blood were examined in 78 patients with colorectal cancer. Out of 10 histopathologic variables, location of venous invasion was most significantly correlated with hematogenous recurrence: the rate (11%) of v0 and/or sm-pm v(+) in 50 patients without the recurrence was significantly lower than that (89%) in 28 patients with the recurrence. On the other hand, the rate (68%) of ss-extra(+) in the latter was significantly higher than that (32%) of the former. The mean values (6 and 14 ng/ml) and positive rates (22 and 48%) greater than 5 ng/ml of p and d-CEA in 50 patients without the recurrence were significantly lower than those (14 and 189 ng/ml, 48 and 96%) in 28 patients with the recurrence. Patients with d-p CEA gradient greater than 5 ng/ml were found, respectively, in 34% of the former and 82% in the latter. The mean value (982 U/l) and positive rate (94%) greater than 37 U/ml of CA19-9 in peripheral blood of 28 patients with the recurrence were significantly higher than those (25 U/ml and 11%) of 50 patients without the recurrence. These results suggest that colorectal cancer patients with high risk of hematogenous metastasis and recurrence are the patients with ss-extra(+), the values of d-CEA, especially d-p CEA gradient, greater than 5 ng/ml and with p-CA19-9 value greater than 37 U/ml.     

Peritoneal Carcinoembryonic Antigen Level for Predicting Locoregional and Distant Spread of Gastric Cancer

Purpose Peritoneal recurrence is not an uncommon cause of death after surgery for gastric cancer, even after surgery with curative intent. This indicates that there is undetected residual disease in the peritoneal cavity. We conducted this study to determine the value of peritoneal and serum carcinoembryonic antigen (CEA) levels and peritoneal washing cytology in predicting the locoregional and distant spread of gastric cancer. Methods We prospectively evaluated 70 consecutive patients with gastric cancer by measuring peritoneal CEA (pCEA) and serum CEA (sCEA) levels and peritoneal washing cytology results, and studying their effect on the histopathologic properties. The effect of the pCEA level on disease-free survival (DFS) and overall survival (OS) was also evaluated in patients treated with curative intent. Results Twenty-one (30%) patients had sCEA levels >10 ng/ml, whereas 25 patients (35.7%) had pCEA levels >10 ng/g protein and 26 patients (37.1%) had positive cytology. The pCEA levels were significantly higher in patients with hepatic metastases (P = 0.034), or serosal (P = 0.028), and peritoneal (P = 0.026) involvement, whereas the sCEA levels were significantly higher only in patients with hepatic metastases (P = 0.04). Similarly, positive cytology was mainly detected in patients with hepatic metastases (P = 0.004). The pCEA levels significantly affected DFS (P = 0.002) and OS (P = 0.01) in 34 patients treated with curative intent. Conclusion Since pCEA levels are more useful for predicting locoregional recurrence, their measurement during surgery may help plan the most appropriate surgical strategy and adjuvant therapy.     

Multivariate analysis of a personal series of 247 patients with liver metastases from colorectal cancer. II. Treatment by intrahepatic chemotherapy

One hundred and seventeen patients with colorectal hepatic metastases had insertion of catheters for infusional chemotherapy. The two-year survival estimate of patients with less than 50% hepatic replacement and no other adverse factors was 37%. Nine of 39 patients in this group are alive at 24 months. The catheters were placed into the hepatic artery (HA), 23; into the portal venous system (PV), 18; into both HA and PV, 64; or into an accessory HA following ligation, 12. Fifty-nine patients had ligation of the common HA also. The 30-day postoperative mortality rate was 1.7% (2/117) and morbidity was 37.6%. The majority of complications were related to fever (61%, 27/44). Over the past 2 years, 87% of patients have been discharged within 10 days following surgery. Preoperative CEA ranged from 0.5-12,150 ng/ml (median 165 ng/ml); 93% (78/84) had plasma CEA levels exceeding 5 ng/ml. All patients had careful intraoperative staging: per cent hepatic replacement (PHR) ranged from 5-95% (median 60%); portal, celiac, or periaortic lymph node metastases were observed in 31% (36/117). Initial intrahepatic chemotherapy programs consisted of either CAMF (9 patients), MAFL (60 patients), BFS (22 patients), continuous infusion FUDR (14 patients), or miscellaneous drugs (4 patients). Median survival time of 109 evaluable patients was 11.5 months. The effect of 20 variables on the observed survival time was analyzed using a multivariate proportional hazard model. Three variables were found to have influenced survival: PHR emerged as the most significant, p = 0.000001. Increased PHR was associated with decreased survival time. Lymph node metastases and prior chemotherapy were prognostic factors also, p = 0.0006 and p = 0.03, respectively. No patient with PHR greater than 80% lived more than 8 months. Utilization of these variables would appear to be necessary for accurate stratification and evaluation of future chemotherapy trials in patients with colorectal hepatic metastases.     

Value of Carcinoembryonic Antigen Assay in Predicting Hepatic Metastases, Local Recurrence, and Survival After Curative Resection of Colorectal Cancer

Purpose We measured carcinoembryonic antigen (CEA) levels in peripheral and portal venous blood, and bile from patients with colorectal cancer, to determine its role in predicting hepatic metastases, local recurrence, and survival. Methods The subjects were 73 patients who underwent curative surgery for colorectal cancer. Results The median serum, bile, and portal CEA levels were significantly lower in 5-year survivors than in patients in whom hepatic metastases or recurrent disease subsequently developed. The CEA level in portal blood and bile was a good indicator of hepatic metastases, with sensitivity of 92% and 100%, respectively. However, the accuracy of any CEA measurement for predicting hepatic metastases, local recurrence, or 5-year survival did not exceed 70%. Conclusions None of these CEA measurements is accurate enough to be the basis of a management decision. Thus, we suggest that CEA measurement be used to assist in the prediction of a high risk of the development of hepatic secondaries and that these patients are followed up closely after curative resection.     

Plasma DNA is more reliable than carcinoembryonic antigen for diagnosis of recurrent esophageal cancer

BACKGROUND: Carcinoembryonic antigen (CEA) and plasma DNA are known to be elevated in patients with esophageal cancer and are higher in patients with disseminated disease. The sensitivity and specificity of these markers in the diagnosis of recurrent esophageal cancer have not been compared. STUDY DESIGN: Plasma DNA was measured using polymerase chain reaction in 45 patients with esophageal cancer and 44 asymptomatic volunteers. The 95(th) percentile (19 ng /mL) in the volunteers was used to define normal. Thirty-nine patients had localized cancer and underwent resection, and six had disseminated disease at operation. Plasma DNA was measured preoperatively in all patients, with serum CEA measured in 31. Plasma DNA was measured sequentially during followup in 21 patients, including 7 who developed recurrence. CEA was measured in 14 of 21 patients who had sequential plasma DNA measured and in 6 of 7 patients with recurrence. CEA levels greater than 5.0 ng/mL were used as cut-off. RESULTS: Plasma DNA was more sensitive than CEA for detecting unresectable esophageal cancer (100% versus 40%), but it had a lower specificity (22% versus 89%).The positive predictive value (19% versus 40%) and negative predictive value (100% versus 89%) were similar for plasma DNA and serum CEA, respectively. Plasma DNA was also more sensitive than CEA in detecting recurrent esophageal cancer (100% versus 33%). The specificity and positive predictive values were 100% for both tests, but the negative predictive values were higher for plasma DNA. Plasma DNA rose before there was clinical evidence of recurrence in 67% compared with only 17% for CEA. CONCLUSIONS: Elevated plasma DNA is an extremely reliable indicator of the presence of recurrent disease, and, in the majority of patients, it rises before clinical evidence of recurrence. In contrast, a normal CEA should be interpreted cautiously, because it does not exclude recurrent disease.     

The usefulness and limitations of CEA assay in the management of colorectal cancer

We investigated the usefulness and limitations of the measurement of CEA in the evaluation of tumor resection and the detection of recurrence in colorectal cancer patients. Preoperatively, 46 of 90 patients (51.1%) had CEA values of 5.0 ng/ml or higher. The percentage of patients with elevated CEA in whom the CEA values returned to normal one month postoperatively was significantly higher in those who had undergone a curative resection than in those who had undergone a non-curative resection (p<0.02). Among patients with normal CEA values, the changes were nil or only slight in CEA values, one month postoperatively Among 28 with recurrences, 24 (85.7%) had CEA values of 5.0 ng/ml or higher. All 11 with liver recurrences had values of 10.0 ng/ml or higher. In 4 with liver recurrences and in cases where CEA measurements were made, CEA values were found to be abnormal 3 to 10 months before the recurrences and a rapid elvation occurred for a short period. However, 4 out of 10 with local or lymphnode recurrences showed normal CEA values. CEA measurement was useful in detection of liver recurrences, but not so useful in detecting local or lymphnode recurrences.     

Roôle of carcinoembryonic antigen in bronchial carcinoma.

It has been reported that lung cancer patients often have raised carcinoembryonic antigen (CEA) levels but the significance of this in diagnosis and follow-up has yet to be established. The results of 256 preoperative investigations in patients with lung cancer are reported. Sequential values after radical surgery and chemotherapy and immunotherapy have been performed in 57 patients during treatment and outpatient follow-up. Ninety-nine per cent of preoperative values were more than 5 ng/ml and 41% greater than 15 ng/ml. Only 6% reached diagnostic levels for malignancy (greater than 52ng/ml) and adenocarcinomas formed 47% (7 out of 15) of these. Sequential estimation in patients during and after treatment showed fluctuations which were related to disease status in 7 (32%) of 22 who have developed secondary disease. In three patients levels of greater than 50 ng/ml preceded clinical evidence of recurrence, and two patients have developed very high levels but have not yet developed other evidence of recurrent disease. It is concluded that raised CEA levels in lung cancer are infrequent, but in those patients who have or develop raised levels sequential investigation may be of value in monitoring response to treatment and clinical coourse.     

Neutron radiotherapy for recurrent pleomorphic adenomas of major salivary glands.

INTRODUCTION: Pleomorphic adenoma is the most common neoplasm arising in the salivary glands. Surgical management is the primary therapeutic modality. With the use of modern surgical techniques, recurrence is infrequent, and facial nerve sparing is the norm. However, for patients with recurrent disease, the risk of further relapses is increased with surgical resection alone, particularly for those patients in whom multiple recurrences have already occurred. The role of adjuvant radiotherapy in this setting remains uncertain. Although neutron radiotherapy is superior to conventional radiotherapy for malignant salivary gland tumors, its role in the treatment of pleomorphic adenomas is less well defined. We report our experience using this modality for high-risk, recurrent pleomorphic adenomas. METHODS: Sixteen patients were treated with neutron radiotherapy for recurrent pleomorphic adenomas of major salivary glands from 1986 through 1993. The median age at diagnosis was 33 years (range, 11-77 years); median age at the time of neutron radiotherapy was 52 years (range, 22-77 years); median number of prior surgical procedures was 3 (range, 1-6); median duration from initial diagnosis to radiotherapy was 14.5 years (range, 3 months-30 years); median follow-up was 83 months (range, 9-144 months). The median period at risk for survivors was 96 months (defined as the interval from completion of neutron radiotherapy to last follow-up). Ten patients had evidence of gross residual disease at the time of treatment as determined by imaging studies, with nine patients having multinodular disease. RESULTS: The 10-year actuarial survival was 79%. One patient died from lung metastases 9 months after treatment; one patient died from a liver tumor of uncertain origin, but the histology could not rule out a metastasis from the previous pleomorphic adenoma; and one patient died from recurrent disease at the base of skull. The 15-year actuarial locoregional control rate was 85%. One of the two patients with locoregional recurrence had a malignant transformation into an adenocarcinoma. No statistical difference in 15-year actuarial survival (75% vs 83%, p =.82) was found comparing patients with gross residual disease vs microscopic residual disease. The actuarial 15-year locoregional control was 76% for patients with gross residual disease vs 100% for those with microscopic disease. The 15-year actuarial risk of RTOG/ESTRO nonaudiologic grade III/IV complications was 21%. No facial nerve injuries were observed as a direct consequence of neutron radiotherapy. CONCLUSIONS: Neutron radiotherapy offers both excellent local control rates and survival rates in patients with multiply recurrent pleomorphic adenomas that are not candidates for surgical resection, even in the presence of gross residual disease. The treatment-related morbidity is acceptable. Malignant transformations and metastases, although uncommon, may be observed in this tumor.     

Can Biliary Carcinoembryonic Antigen Identify Colorectal Cancer Patients with Occult Hepatic Metastases?

Background Twenty-five percent of radically treated colorectal cancer patients already have occult hepatic metastases (OHM) that will later be observed during postoperative follow-up. Instrumental examinations, i.e., intraoperative ultrasound or Doppler perfusion index, have not improved diagnosis. As carcinoembyonic antigen (CEA) levels are useful to reveal hepatic metastases from colorectal cancer, determination of CEA in the bile rather than the blood may allow preclinical diagnosis of OHM thanks to the reduced volume of bile. Methods One hundred radically treated colorectal cancer patients were enrolled in the study. Bile was withdrawn from the gallbladder intraoperatively and biliary CEA levels determined using an immuno-enzymatic method (normal value 0–5 ng/ml). Eighty-nine fully evaluable patients were followed up for three years postoperatively to monitor hepatic metastases. Preoperative blood CEA, lymph node metastases and biliary CEA were compared in order to assess which procedure was more efficient in identifying patients who would develop hepatic metastases. Results Eleven of the 89 evaluable patients developed hepatic metastases: 9/11 presented elevated biliary CEA levels (mean: 12.73; range: 5.1–26.2); 8/11 had high preoperative blood CEA values; and 9/11 were at anatomopathological stage N+. In the 78 patients who did not develop hepatic metastases, biliary CEA was within normal limits in 73/78, preoperative blood CEA was normal in 60/78, and 58/78 patients were at anatomopathological stage N−. Hence, the sensitivity of biliary CEA was 81.8%, specificity was 93.6%, and diagnostic accuracy was 92.1%. Conclusions Determination of biliary CEA seems to be more efficient in identifying patients presenting OHM who require frequent clinical examinations or adjuvant cancer treatment.     

Correlation between the results of carcinoembryonal antigen (CEA) test and the clinical stage of colorectal carcinoma

Correlation between results of CEA test and clinical stage of colorectal carcinoma is described. No correlation was found between the different stages and the actual CEA titre. Normalization of an increased preoperative serum CEA level indicated, however, nearly always the radical character of the intervention. Critically high (above 30 ng/per ml) CEA value observed in Dukes' stages C and D can be considered bad prognostic signs. Patients like these died within one year. Results of CEA tests are also useful complementary data contributing to the diagnosis of recurrence or distant metastases.     

CEA levels of draining venous blood and draining-peripheral CEA gradient in colorectal cancer patients: correlation with postoperative survival

Correlation between preoperative CEA levels in draining venous blood (d CEA) and draining-peripheral (d-p) CEA gradient, and postoperative survival of 94 patients with colorectal cancer patients was examined. The positive rates of d CEA and d-p CEA gradient greater than 5 ng/ml (55.9% and 37.2%) in 59 alive patients were significantly (p less than 0.05) lower than those (77.1% and 57.1%) in 35 patients died of cancer recurrence within 4 years. Survival curve of the patients with positive d CEA and d-p CEA gradient were significantly (p less than 0.01) lower than those of the patients with negative d CEA and d-p CEA gradient. Survival curve of the patients with d-p CEA gradient greater than 10 ng/ml was significantly (p less than 0.001) lower than that of the gradient less than 10 ng/ml, and 4-year survival rates were 37.5% in the former patients and 68.3% in the latter patients. These results suggest that d CEA and d-p CEA gradient may be used as prognostic indicators of colorectal cancer patients. Clinically, the patients with positive d-p CEA gradient greater than 10 ng/ml are necessary to be treated as patients having very poor prognosis.