John P. Minton

Results of a 400-patient carcinoembryonic antigen second-look colorectal cancer study.

Four hundred patients with resectable colon and rectal cancers were operated on by 37 surgeons at 31 institutions. Patients were monitored with carcinoembryonic antigen (CEA) level determinations and clinical examinations. One hundred thirty patients had recurrences, and 75 were reoperated on, with 43 reoperations CEA‐directed and 32 clinically directed. Two of 75 died within 1 month after the second operation. Twenty‐two second‐look patients remain free of disease 5 years after their second operaton. The highest resectability of recurrent cancer occurred in patients with a CEA level below 11 ng/ml in whom the CEA level was determined at intervals of 1 to 2 months. Cancer 55:1284‐1290, 1985.

CEA-directed second-look surgery in the asymptomatic patient after primary resection of colorectal carcinoma.

Since 1971, serial carcinoembryonic antigen (CEA) levels have been measured to monitor patients after primary resection of colorectal cancer. Based solely on a rise in CEA level above the baseline established after primary resection, 146 patients were readmitted to the hospital. Chest films, liver-spleen scan, colonoscopy, bone scan, abdominal and pelvic CAT scan, and hepatic arteriograms were performed, and elevated CEA levels were confirmed before reexploration was undertaken. In the 146 patients, 139 (95%) had recurrences, and 81 (58%) of these were resectable for potential cure. Two of the first 22 patients re-explored between 1971 and 1975 are still living 11 and 14 years after second look; of 45 patients reoperated upon from 1976 through 1979 and followed for at least 5 years, 14 (31%) are still living. A rise in CEA above the baseline established after primary resection proved to be a sensitive indicator of recurrence and prompted reexploration before symptoms developed. Early alternative therapy was begun in patients with unresectable recurrences.

Complications associated with mastectomy.

Mastectomy-associated complications are presented in the various time periods they become evident. These problems may relate to preoperative decisions and can occur intra-operatively or be delayed for many years. The recognition and management of complications are discussed, with a special emphasis on their prevention.

The USE of CEA as an early indicator for gastrointestinal tumor recurrence and second‐look procedures

Since 1972 plasma CEA levels of 25 cancer patients have been assayed to evaluate the reliability of CEA as an early indicator of recurrent gastrointestinal cancer. Identification of significant elevations in CEA levels required definition of exactly what a given value meant. Intraassay and interassay accuracy was determined and graphed as a CEA NOMOGRAM, which measures the observed CEA level against the 95% confidence limits for that observation and thus can be used to identify statistically significant increases. A statistically significant rise above a baseline value established by the NOMOGRAM proved to be a correct indicator of tumor recurrence in 22 (88%) of 25 patients who underwent second‐look intraabdominal operations (22 colorectal, 2 gastric, and 1 pancreatic). In each case, other accepted procedures, such as liver enzymes, scans, and x‐rays, were nondiagnostic. Of the 22 patients with proved tumor recurrence, 16 (73%) had distant metastases and 6 (27%) had localized tumors. One patient remains tumor‐free three years after second‐look operation and has had no significant change in CEA levels. More frequent serial CEA determinations combined with sound clinical judgment should facilitate earlier detection of recurrent gastrointestinal cancer.

A phase III study comparing the clinical utility of four regimens of 5-fluorouracil: a preliminary report.

A clinical trial involving 462 colon, rectum, and breast cancer patients randomized among four different dosage regimens of 5‐FU (an intravenous loading course, a weekly intravenous schedule, a nontoxic schedule, and an oral schedule) has shown a significantly better response among colon‐rectum cancer patients for the intravenous loading course. In addition, duration of response and time to progression are also significantly better. Overall survival is approaching significance for the colon rectum group (p value .082). In contrast, breast cancer patients show little difference between treatments. Toxicity is somewhat higher for the loading course.

DTIC and combination therapy for melanoma: III. DTIC (NSC 45388) Surgical Adjuvant Study COG PROTOCOL 7040.

A prospectively randomized study of postoperative chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC) was conducted by the Central Oncology Group from 1972 until 1976. Of 174 patients operated upon for melanoma and entered into the study, 87 were randomly selected to receive DTIC, four courses in 12 months, at 4.5 mg/kg/d × 10. One‐hundred‐sixty‐five (95%) of the cases were evaluable, including 40 high risk Stage I, 96 Stage II, and 29 Stage III cases. At a median follow‐up period of 2.5 years, the control group had a better median disease‐free interval (40 weeks vs. 73 weeks), median survival time (103 weeks vs. 133 weeks), and percentage of patients living free of disease (28% vs. 44%) than the DTIC‐treated group. While disease‐free interval appeared to be improved in the 25% of patients on DTIC therapy who developed thrombocytopenia, the overall effect of postoperative DTIC therapy was apparently not beneficial (P < 0.05).

The use of serial CEA determinations to predict recurrence of colon cancer and when to do a second‐look operation

The concept of second‐look surgery was introduced by Wangensteen 25 years ago, and 17% of patients were reported to be converted to a cancer‐free state. Instead of an arbitrary time interval for reoperation, serial CEA values were used as the indicator of colon cancer recurrence and second‐look operation. Twenty‐two retrospective and 18 prospective patients were evaluable. There was no operative mortality. The CEA Nomogram was used to determine whether the CEA change was significant. All patient‐samples were analyzed in duplicate, stored, and compared with the most recent sample; therefore, each patient served as his own control. The prospective results emphasize the importance of minimizing the time delay between a significant change in CEA values and reoperation. Equally important are the frequency of serial determinations (every one or two months), a thorough understanding of the limitations of the CEA radioimmunoassay, and the clinical condition of the patient.

Carcinoma in a Colon Conduit Urinary Diversion

In recent years urinary diversion by means of the colon conduit has gained popularity because of the failure to exhibit reflux and the lower incidence of stomal stenosis. However, colon conduit diversion may be associated with adenocarcinoma, as is ureterosigmoidostomy. We report the first occurrence of adenocarcinoma in a colon conduit and, perhaps more important, in a colon conduit in which there had never been a fecal stream.

A retrospective and prospective study of serial CEA determinations in the early detection of recurrent colon cancer

The results of the present study emphasize the importance of minimizing the time delay between a significant elevation in CEA and a second-look operation. Equally important are the frequency of serial determinations, a thorough understanding of the limitations of the assay, and careful evaluation of the clinical condition of the patient.

Observations on the postoperative tumor growth behavior of certain islet cell tumors.

Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angingram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign.