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Biomedical subjects

E D Holyoke

Publications and source records attributed to E D Holyoke.

At least 73 records · Page 4Linked to original sources

Isolation of glycoprotein antigen from ascites fluid of pancreatic carcinoma.

A glycoprotein antigen from the ascites fluid of pancreatic carcinoma has been isolated with the use of perchloric acid extraction and chromatographies on Sepharose 4B, DEAE-Sephadex, and DE52, followed by Sephadex G-200. The purified glycoprotein was found to be homogenous by sodium dodecyl sulfate polyacrylamide gel electrophoresis. A molecular weight of 185,000 dattons was determined by gel filtration. The molecule contained 55% protein and 45% carbohydrate. Both the amino acid and carbohydrate compositions were different from those of carcinoembryonic antigen. This glycoprotein antigen of pancreatic cancer cross-reacted with anticarcinoembryonic antigen; however, the antiserum prepared from this antigen did not react with carcinoembryonic antigen. The biological significance of this glycoprotein in pancreatic cancer is being studied.

Antigens, Neoplasm↗

BCG immunotherapy in patients with malignant melanoma.

Twenty-one patients with malignant melanoma received immunotherapy with BCG. Thirteen patients had adjuvant immunotherapy on a monthly schedule. Of these, eight with regional lymph node metastases (stage III) had been treated by lymphadenectomy. Two of the stage III patients had tumor recurrences within one year, while six are alive and free of melanoma at a median interval of 22 months. The remaining five patients (stage I or II) had level 4 or 5 (Clark classification) primary lesions. Their average tumor-free survival has been 18 months, but there was one regional recurrence in six months. Eight patients received intralesional treatment with BCG. The extent of local response correlated inversely to the stage of their disease. Higher doses of BCG or multiple simultaneous injections into the same lesion did not produce complete resolution of nodules in patients with far-advanced melanoma. In none was the course altered by intralesional therapy.

BCG Vaccine↗

Intraluminal, lymph node, hepatic, and serum levels after intraluminal and intramural injection of 5-fluorouracil in the dog colon.

The tissue levels of 2-14C 5-fluorouracil were compared after three routes of administration in the colon of fifteen dogs. "Simple" submucosal injection resulted in higher levels in the colonic wall, abdominal lymph nodes, and liver than did rapid intravenous injection. Intraluminal administration demonstrated that the appearance of 5-FU was prompt and that significantly higher levels continued in the colonic wall and liver, but nodal levels were markedly lower.

Animals↗

Semi-automated method for the enumeration of cytotoxicity results.

This communication provides information on the design and use of a counting machine that enumerates adherent cells in cytotoxicity assays. To date, investigators have relied on inverted microscopes or quantimat automatic image analysis. The former method is tedious and time consuming while the latter method is prohibitively expensive. The counting machine which consists of projection microscope attached to an electronic counter is as accurate as the inverted microscope but is both less tedious and less time consuming.

Autoanalysis↗

Murine colon adenocarcinomas: methods for selective culture in vitro.

Two murine colon adenocarcinoma cell lines were established from primary cultures. The MCA-38 cell line was begun by treatment of the primary culture with trypsin to remove the fibroblastoid elements. The MCA-36 epithelial cells were sensitive to trypsin; therefore, the growth medium of MCA-36 primary cultures was augmented with collagenase to release the tumor-cell elements from the fibroblast network. These tumor elements were dissociated with trypsin and placed in tissue culture. Each cell line was cultured for at least 10 passages in vitro and gave rise to tumors when reimplanted in vivo.

Adenocarcinoma↗

Carcinoembryonic antigen (CEA) as a prognostic and monitoring test in clinically complete resection of colorectal carcinoma.

The prognostic and postoperative monitoring capabilities of the CEA assay were compared to pathological staging of the operative specimens, clinical followup including endoscopy, radiology and scanning techniques, as well as DNCB skin testing and laboratory enzyme determinations (alkaline phosphatase and transaminase). A total of 46 patients with curative resection for colorectal carcinoma were studied. This included 23 patients with recurrent tumors compared to 23 long-term survivors without signs of recurrence at the time of the study. Preoperative CEA determinations were a good prognostic tool comparable to pathological staging of the specimen. Post operative CEA monitoring was the earliest sign of recurrence in 14 of 23 patients and was positive at the time of recurrence determined by other methods in 20; it was negative in only three cases. The incidence of false positive results among the non recurrent group became a lesser problem when repeated elevated values were required before considering the patient as having a recurrence. From these data, it seems reasonable to propose the use of a second-look operation in patients with maintained elevation of circulating CEA and no clinical signs of tumor presence, if we are to treat recurrence at an early stage. Chemotherapy would be an alternative way to deal with this problem, since the absence of clinical signs in general correlate with small bulk of tumor which at this time may be more susceptible to chemotherapeutic agents.

Adult↗

Evaluation of forequarter amputation in malignant diseases.

Twenty-one forequarter amputations were performed at our institute during a 15 year period for soft tissue sarcoma, osteosarcoma, recurrent malignant melanoma and epidermoid carcinoma. Two patients in this group who have had recurrent carcinoma of the breast with a painful, edematous and ulcerated upper extremity were palliated and had significant relief. The over-all five year survival rate following this procedure for curative intent was 25 per cent. There were no five year survivors of unclassified sarcoma, myosarcoma and recurrent malignant melanoma. Thus, we do not recommend this procedure for recurrent malignant melanoma, although it can be performed as a palliative measure. Since most of the patients with malignant bone tumors, unclassified sarcoma and myosarcoma have systemic metastasis develop within two to eight months after this procedure, new methods should be explored to detect early metastasis before undertaking this psychologically traumatic procedure. Adjuvant chemotherapy and other modalities of adjuvant therapies are recommended in this group with poor prognosis. A local recurrence after this amputation in patients with unclassified lesions and myosarcoma should be considered as an indication of systemic metastasis.

Adolescent↗

Hemipelvectomy.

Hemipelvectomy was performed in 50 patients with malignant neoplasms of the upper part of the thigh and pelvis. Although not technically difficult, the operation is associated with considerable blood loss. Postoperative complications are frequent, the greatest morbidity resulting from skin flap necrosis. Symptomatic phantom limb is as occasional late problem. Of 37 patients resected for cure prior to 1969, 14 were alive five or more years postoperatively. Five of these long-term survivors subsequently died of metastases. Patients with fibrosarcoma and chondrosarcoma had the best survival. Six other patients underwent palliative hemipelvectomy for intractable pain, with gratifying results. Hemipelvectomy is an important, useful operative procedure in selected patients.

Adolescent↗

CEA as a monitor of gastrointestinal malignancy.

Ninety-four patients with carcinoma of the colon have been followed with serial determinations of plasma CEA (carcinoembryonic antigen) levels over a 3-year period using the Hansen assay. Nine hundred twelve CEA determinations have been made in these patients. Plasma CEA levels rose in 90% of the instances of clinical progression documented in these patients. In 30% of patients, this rise indicated progression 6 months or more before it was detected by standard clinical methods. Unfortunately, a few patients never developed elevated CEA levels even though disease clearly progressed. False positive results have also been encountered, with significant elevations occurring in patients who have since remained without evidence of disease for several months. Our data indicate that at least two sequential elevated CEA values, the second being higher, must be a minimal criterion for consideration of possible progression of disease. Even with this standard, we have encountered false positive results in 10% of our patients, indicating recurrence or progression where none has occurred clinically. CEA measurement is of limited usefulness for 30 days after curative surgery, because the elevation of CEA levels due to the original amount of tumor present as well as due to surgery per se may persist for this length of time in a significant number of patients. On the other hand, CEA levels have responded to chemotherapy in close correlation with observed clinical course in those patients with metastatic disease treated in this series. Initial pretherapy CEA values have so far proved to be good prognostic indicators of disease course following complete resection. With an initial CEA value of less than 2.5 ng/ml of plasma, recurrent has been rare (1/20). If the pretreatment CEA was greater than 7.0 ng/ml, it has been the rule (7/9).

Alkaline Phosphatase↗

End results of radiation therapy, alone and combination with 5-fluorouracil in colorectal cancers.

The authors retrospectively analyzed the results of irradiation in 148 cases of primary inoperable and recurrent adenocarcinoma of the colon and rectum treated at the Department of Radiation Therapy, Roswell Park Memorial Institute between 1962 and 1970. This group includes 95 recurrences and 53 inoperable primaries. Uninterrupted radiotherapy was used in 118 cases and split-course technique in 30 cases. Eleven patients received combined radiotherapy and surgery. Seventy-eight patients received a combination of 5-fluorouracil (5-FU) and irradiation. The response rate and survival of individual groups is discussed in detail. This study indicated that perineal recurrences should receive whole pelvic irradiation in addition to perineum field. Split-course technique appeared to yield a better survival than the uninterrupted course. The best 5-year survival rate (64%) is found in the group treated with a combination of radiation and surgery. For locally advanced, inoperable cancers, split-course technique, combined 5-FU and irradiation gave the best results, achieving longer palliation with improved quality of life and sometimes yielding cure (5-year survival).

Colonic Neoplasms↗

Simultaneous determination of plasma and urinary carcinoembryonic antigen levels.

The results of simultaneous plasma and urinary CEA levels in 14 patients are described. The aim was to determine whether urinary CEA derived from plasma or arose independently in the urinary tract. The method of reductio ad absurdum is followed. It is assumed that CEA in the urine is derived from plasma, and CEA clearance values for each patient are calculated. These varied widely from zero to a theoretical infinity. On this basis and from previous experimental evidence, it is concluded that urine is independent of plasma CEA. The finding, however, in some individuals of "anti-CEA"-like factor(s) distorting urinary CEA determination makes for some reservations about the safety of the conclusion. It is, however, certain that with the presently available technology, present urinary and plasma CEA values cannot be correlated.

Carcinoembryonic Antigen↗

Rectocolic reconstruction via a modified Kraske approach.

In carefully selected patients, the sacrococcygeal approach (Kraske's operation) with rectal colostomy can save a patient from abdominoperineal resection without loss of continence. This procedure is also useful in the management of rectal strictures that occasionally occur after leaks from the anastomosis of a low anterior resection of the rectosigmoid colon. Three illustrative cases are presented and discussed.

Adenocarcinoma↗

The posterior approach to rectal anastomoses.

The posterior approach to the rectum provides excellent exposure for benign lesions which are too high to be excised through the anus but too low to be excised transabdominally. As an adjunct to low anterior resection, it broadens the scope of the procedure without compromising the requirements of a proper operation for cancer.

Humans↗

Cystadenoma of the pancreas.

Five patients with cystadenoma of the pancreas were seen during a period of 22 years at this institute. This rare benign tumor occurred predominantly in middle age women, with the presenting symptoms of pain and an epigastric mass, but without a history suggestive of pancreatitis or abdominal trauma. Selective celiac and superior mesenteric antiography is helpful in establishing the diagnosis. If this cystic tumor is not recognized and adequately treated, the surgeon may miss the opportunity for cure. Cystadenoma should be suspected when a cystic mass arising from the body or tail of the pancreas is encountered without evidence of metastases. Although surgical extirpation is the preferable treatment, undue risks should not be undertaken because of the slow growth rate of this benign tumor. Due to the known association of this tumor with other malignant lesions, diabetes mellitus as well as multicystic tumors of the liver and kidneys, these patients should be thoroughtly investigated.

Adult↗

Evaluation of palliative resection in advanced carcinoma of the stomach.

A retrospective study of 140 patients with adenocarcinoma of the stomach seen at Roswell Park Memorial Institute during a 5 year period revealed that 112 patients were TNM Stages III or IV. A palliative resection of the stomach was done in 39 patients; the other 73 did not undergo resection. Patients who had palliative resection for stages III and IV carcinoma of the stomach had a prolonged mean survival rate, as compared with those with similar stage of disease who did not have palliative resection, regardless of an additional treatment such as feeding procedures, gastroenterostomy, chemotherapy, and radiation therapy. This significance was noticed regardless of age, sex, and histological differentiation of the tumor. Chemotherapy significantly increased the survival rate in the unresected group but failed to show this effect in the resected group.

Adenocarcinoma↗