Serum CA 125 concentrations in patients with benign ovarian tumours.

Serum CA 125 concentrations have been measured in 115 patients with histologically confirmed nonmalignant pelvic disease, that is, serous cystadenoma (n = 56), mucinous cystadenoma (n = 14), fibroma (n = 33), thecoma (n = 8), and Brenner tumour (n = 4). Increased CA 125 concentrations (> 35 KU/L) were found in 14 patients, with a range of 46-891 KU/L, a mean of 205 KU/L, and a median of 97 KU/L. The highest values were found in patients with ascites. Serial measurements in one patient showed a fall in the 2 days immediately after surgery, over the next 3 days showing a two- to three-fold increase, followed by a slow return to normal over the next 7 weeks. Elevated CA 125 levels may not indicate ovarian malignancy and do not differentiate between benign and malignant pelvic masses.

A profile of serum CA 15-3, carcinoembryonic antigen, alkaline phosphatase, and gamma-glutamyl transferase levels in patients with breast cancer.

The CA 15-3 and CEA concentrations and the alkaline phosphatase (ALP) and gamma-glutamyl transferase (Gamma GT) activities of serum from 78 patients with breast cancer have been measured. The patients included 27 with localised breast cancer, 19 who had been treated for breast cancer but were now disease-free, 17 with liver metastases, 8 with bone metastases, and 7 with disseminated breast cancer but with neither metastases to the liver or bone. As an indicator of localised breast cancer the predictive value of an increase in CA 15-3 concentration was 93%. As an indicator of metastatic breast cancer the predictive value of an increased CA 15-3 was 62%, whereas the predictive values of an increase in both CA 15-3 and CEA and an increase in CA 15-3, CEA, and ALP 88% and 100%, respectively. A normal CA 15-3 excluded metastatic breast cancer and a normal gamma-GT excluded liver metastases. The four tests together provide a set of markers for use in the follow-up of patients with breast cancer.

Hormonal treatment of pancreatic carcinoma: a phase II study of LHRH agonist goserelin plus hydrocortisone.

Eighteen consecutive patients with measurable locally advanced or metastatic pancreatic adenocarcinoma were treated with goserelin (Zoladex) 3.6 mg subcutaneously every 4 weeks. Hydrocortisone 20 milligrams twice daily was commenced with the second injection of goserelin. Objective tumour response was monitored by computerised tomography of the abdomen. There was no objective remission in disease sites. Serial measurements of serum tumour markers showed no reduction in serum CA 19-9 and CA 195 concentrations. The median duration of survival of all cases was 5 months. Administration of goserelin resulted in significant reductions in oestradiol, testosterone, androstenedione in males and reductions in FSH and LH in both males and females. The addition of hydrocortisone resulted in further reductions of androstenedione and testosterone levels in males. Thus goserelin showed no anti-tumour effect, but concentrations required for direct inhibitory effects may be higher than those required to produce effects on hormone suppression.

Serum CA 12-5 concentrations and CA 12-5/CEA ratios in patients with epithelial ovarian cancer.

In attempts to increase the specificity of the CA 12-5 test the ratio of CA 12-5 and CEA concentrations has been determined in 155 cancer patients, all of whom had an increased serum CA 12-5. The patients included 47 with epithelial ovarian cancer, 38 with colorectal cancer, 24 with cervical cancer, 20 with lung cancer, 17 with gastric cancer, and 9 with pancreatic cancer. The CA 12-5/CEA ratio in serum of patients with ovarian cancer ranged from 30 to 920 (mean 251), whereas in other types of cancer the highest ratio was 240 and the mean was 13. All 47 patients with ovarian cancer, but only 7 of the 108 patients with other types of cancer, showed a CA 12-5/CEA ratio greater than 25. About 10% of the patients with gastric or colorectal cancer but none of those with other types of cancer showed an increased ratio. As the predictive value of a CA 12-5/CEA ratio of less than 25 excluding ovarian cancer is 100%, we recommend measuring the CEA concentration in all those with increased CA 12-5 and calculation of the CA 12-5/CEA ratio.

Neuron-specific enolase during chemotherapy of small cell lung cancer.

Serum neuron-specific enolase (NSE) has been measured in 28 patients with small cell lung cancer (SCLC) and 90 patients with other forms of lung cancer (NSCLC), i.e., 28 with adenocarcinoma and 62 with squamous cell carcinoma. Increased NSE (greater than 12.0 micrograms/liter) was found in 71.4% of SCLC patients and in 22.2% of NSCLC patients. The predictive value of an increased NSE in identifying SCLC was only 50%, whereas the predictive value of a normal NSE in differentiating SCLC for NSCLC was 91%. Serial studies during chemotherapy of SCLC patients showed that the doubling time of NSE ranged from 7 to 127 days and the mean apparent half-life (AHL) of NSE to be 14 days. AHL values in excess of 20 days suggest that the tumour is not in full remission. We believe that measurement of serum NSE and calculation of the AHL and DT are valuable in identifying the effectiveness of chemotherapy in patients with SCLC.

Assessment of renal toxicity by urinary enzymes in patients receiving chemotherapy with 8-methyl-8-acetylenic-putrescine.

Renal toxicity was assessed in 19 patients receiving methyl acetylenic putrescine (MAP), an irreversible inhibitor of ornithine decarboxylase. Patients received 250 mg t.d.s. for up to 13 weeks. This dose effectively inhibited the target enzyme, as shown by elevations in decarboxylated S-adenosyl methionine levels. No significant nephrotoxicity was observed in these patients as determined by plasma urea, creatinine and creatinine clearance measurements, although minor elevations of the urinary enzymes lactate dehydrogenase, N-acetyl-beta-glucosaminidase, alkaline phosphatase and alanine aminopeptidase were observed. As this could represent sub-clinical renal damage, caution should be exercised when using MAP in combination with other cytotoxic drugs.

Comparative study of the clinical usefulness of prostate specific antigen and prostatic acid phosphatase in prostatic disease.

The clinical usefulness of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) activity measurements has been compared in 45 patients with benign prostatic hyperplasia (BPH) and 132 patients with prostatic carcinoma (PC), 21 of whom had metastatic disease (MPC) and 111 of whom had intracapsular cancer. No BPH patient had increased PAP but 47% had increased PSA. Of the PC patients only 27% had increased PAP and 70% increased PSA. All of the MPC patients had increased PSA but only 62% had increased PAP. Increased PAP was found only in MPC but increased PSA was also found in BPH. In identifying PC, the predictive value of an increased PSA concentration is 83% and an increased PAP activity is 100%. On the other hand, the predictive value of a normal PSA concentration is 51% and of a normal PAP activity only 34%. As the PAP test is much less efficient than the PSA test, it should be discontinued.

Intestinal alkaline phosphatase isoenzyme in patients with primary liver cancer during treatment with N10-propargyl 5, 8-dideazafolic acid (CB 3717).

Serum aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (gamma GT) activities and the serum ALP isoenzyme pattern have been measured in eleven patients undergoing treatment with CB3717. There were increases in the activity of all three enzymes. The ALP isoenzyme pattern showed an increased contribution of the intestinal isoenzyme to the serum ALP activity. This may be due to increased intestinal mucosal leakage or impaired uptake and breakdown of the intestinal isoenzyme by the liver.

The value of tumour marker kinetics in the management of patients with primary hepatocellular carcinoma.

Serum alpha-fetoprotein (AFP) has been measured during chemotherapy of ten patients with hepatocellular carcinoma. Whenever the AFP concentration of a sample was lower than that of the previous sample the apparent half-life (AHL) of the protein was calculated. The biological half-life of AFP is 5 days so that values in excess of this were indicative of continuing or increased synthesis and secretion of AFP. The AHL for AFP provided a means of assessing efficacy of treatment. Increases in AHL generally predicted a rise in serum AFP and give advance warning of the need to change therapy.

Urinary protein and enzyme excretion in patients receiving chemotherapy with the cis-platinum analogs carboplatin (CBDCA, JM8) and iproplatin (CHIP, JM9).

Urinary protein and enzyme excretion was measured in 33 patients with solid tumours receiving chemotherapy with the cis-platinum analogs carboplatin (JM8, CBDCA) and iproplatin (JM9, CHIP). The patients were given up to six courses of the drugs at 4-week intervals, and serial urine samples were collected weekly for periods up to 28 weeks. Overall there was no significant increase in the alkaline phosphatase (ALP), lactate dehydrogenase (LD), and N-acetyl glucosaminidase (NAG) excretion of the first posttreatment samples compared with the pretreatment samples. During the course of treatment there were transient increases in all three enzymes, some quite marked. There was no consistent increase in urinary protein or enzyme excretion during the period of treatment, suggesting that there was no cumulative nephrotoxicity. There was no change in creatinine clearance or urinary beta 2-microglobulin content. Iproplatin appeared marginally more toxic on the basis of elevated NAG and ALP during the second half of the treatment periods compared with the first (P less than 0.01 and less than 0.025, respectively).

Differential reactivity of alpha-fetoprotein with lectins and its usefulness in the diagnosis of various liver diseases.

Serum from 38 patients with liver disease and elevated serum AFP concentration was subjected to affinity chromatography on concanavalin A (Con A) and lentil lectin. More than 70% of the serum AFP of the 18 patients with primary liver cancer (PLC) or the 12 patients with cirrhosis or chronic active hepatitis (BLD) bound to Con A, less than 70% of the serum AFP of 8 patients with metastatic liver disease (MLD) bound to Con A. On the other hand less than 20% of the serum AFP of the BLD patients but more than 20% of the serum AFP of the PLC or MLD patients bound to lentil lectin. Thus reactivity of serum AFP towards Con A and lentil lectin provides a simple test that can be used in the differential diagnosis of BLD, PLC and MLD.

Initial assessment of tumor-associated antigen CA-125 in patients with ovarian, cervical, and testicular tumors.

Serum CA-125, a glycoprotein antigen, has been measured in serum of patients with ovarian cancer, cervical cancer, or nonseminomatous germ-cell tumor of testis. Increased concentrations were found in 21 of 27 patients with epithelial ovarian cancer and two of three patients with ovarian teratoma. Changes in CA-125 concentrations in serum during chemotherapy mirrored the progress of the disease as assessed by clinical and radiological evidence. Although CA-125 provides no real asset for diagnosis, it should have value as a marker for monitoring response to chemotherapy.

Serum human pancreatic elastase I levels in pancreatic disease.

The serum elastase concentration has been measured in 25 healthy individuals, sixteen patients with tumours involving the pancreas, nine patients with acute pancreatitis and nine patients with chronic pancreatitis. The elastase concentrations were increased in those with pancreatic tumours particularly when the head of the pancreas was involved. In acute pancreatitis, the serum elastase showed a proportionally greater increase than did the serum amylase and maintained abnormal levels for a longer period. In six out of nine patients with chronic pancreatitis the serum elastase level was within the reference range for healthy individuals.

Assessment of serum CA 19.9 as a tumour marker in patients with carcinoma of the bladder and prostate.

CA 19.9, a carbohydrate structure definable by a monoclonal antibody, is a useful tumour marker in the serum of patients with gastrointestinal malignancy. We report for the first time an assessment of its value in patients with cancer of the bladder and prostate. Elevated levels were found in six of 12 patients with invasive or metastatic bladder cancer but in only two of eight patients with superficial tumours. All patients with cancer of the prostate had levels within the normal range. A long-term study of its value in monitoring disease activity in patients with cancer of the bladder is warranted.

Serum vitamin B12 levels in patients with primary hepatocellular carcinoma during treatment with CB3717.

Elevated Serum B12 levels were found at diagnosis in five of eleven patients with primary hepatocellular carcinoma. During chemotherapy either with CB3717 or VP16 the serum B12 rose dramatically, in one case reaching levels ten times the upper limit of normal. However, the serum LD activities did not change in parallel with the serum B12 levels suggesting that there was little necrosis of the tumour or the liver. With two out of five patients with other types of cancer the serum B12 levels also increased but less markedly. This data seems to suggest that the serum B12 level may not be as good a tumour marker for hepatocellular carcinoma as has been suggested and indeed may be influenced by the chemotherapeutic agent.

An initial appraisal of the value of serum carbohydrate antigenic determinant (CA 19-9) levels in patients with pancreatic cancer.

Serum CA 19-9 levels have been determined in 20 patients with pancreatic cancer, 18 patients with primary hepatocellular cancer, 15 patients with metastatic liver disease and 10 patients with colorectal cancer. Market elevations 3 times the upper limit of normal were found in all 20 patients with pancreatic cancer, 10 out of 15 with metastatic liver disease and 7 out of 18 with hepatoma. As serum AFP and CEA levels are normal in those with pancreatic cancer, the serum CA 19-9 level provides a sensitive and specific test for this malignancy.

Lentil-lectin-reactive alpha-fetoprotein in the differential diagnosis of benign and malignant liver disease.

Affinity chromatography of serum on lentil lectin bound to Sepharose 4B has been used to identify different forms of alpha-fetoprotein in serum of patients with liver disease. We studied eight patients with non-malignant liver disease, finding that 7-15% of the serum alpha-fetoprotein bound to the lectin. In contrast, for 15 patients with malignant liver disease, 25-83% of the serum alpha-fetoprotein bound to the lectin. Evidently, this simple technique can be used effectively to differentiate these two conditions.

A pleomorphic hepatocellular carcinoma with biochemical features of fibrolamellar hepatocellular carcinoma.

A case of pleomorphic hepatocellular carcinoma with biochemical characteristics similar to those of fibrolamellar carcinoma is described. During chemotherapy there was a marked disorder of vitamin B12 metabolism.