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Biomedical subjects

G H Farr

Publications and source records attributed to G H Farr.

At least 37 records · Page 2Linked to original sources

Prognostic value of c-erbB2 overexpression in axillary lymph node positive breast cancer. Results from a randomized adjuvant treatment protocol.

BACKGROUND: This study was designed to evaluate the prognostic importance of c-erbB2 overexpression in a standardized cohort of patients with axillary lymph node positive breast cancer. METHODS: Paraffin embedded primary breast cancers from 354 patients with axillary lymph node positive breast cancer, treated on a North Central Cancer Treatment Group adjuvant protocol, were studied immunohistochemically. c-erbB2 staining was classified as negative, weak (1+), moderate (2+), or strong (3+) and was assessed for effectiveness as a predictor of outcome in univariate and Cox model multivariate analyses. RESULTS: Twenty percent of specimens exhibited moderate or strong c-erbB2 staining. The median disease free survival period of the strong staining group was 2.9 years, compared with 7.1 years for all other patients (P = 0.01). The median overall survival for the strong staining group was 5 years, compared with 12 years for all other patients (P = 0.03). A definite correlation was noted between degree of nodal involvement and the likelihood of strong c-erbB2 staining (P = 0.001). There was also a significant correlation between c-erbB2 staining and higher nuclear grade and estrogen receptor negativity. In a multivariate analysis, c-erbB2 staining was not a significant predictor of either disease free survival or overall survival. CONCLUSION: According to this analysis, the strong correlation between c-erbB2 expression and degree of nodal involvement, higher grade disease, and estrogen receptor negativity suggests expression of this protooncogene product in a biologically more aggressive form of breast cancer. In a multivariate analysis, c-erbB2 expression was not an independent prognostic factor. Thus, c-erbB2 assessment did not appear to add significantly to the information provided by currently available standard disease parameters.

Breast Neoplasms↗

Nodular regenerative hyperplasia: a controversial indication for orthotopic liver transplantation.

Nodular regenerative hyperplasia of the liver is an uncommon cause of portal hypertension. Patients with nodular regenerative hyperplasia have signs and symptoms of portal hypertension, without evidence of hepatocellular failure or encephalopathy. We report the case of a 44-year-old woman with recurrent esophageal bleeding and refractory ascites who had a history of hemosiderosis, hepatitis C, and chronic renal allograft rejection. Our preoperative diagnosis was cirrhotic end-stage liver disease and end-stage renal disease for which the patient underwent combined hepatic and renal transplantation. Her portal hypertension symptoms resolved, and her renal function has been normal for 18 months of follow-up. Histologic examination of the liver revealed nodular regenerative hyperplasia, and a review of the literature regarding the surgical management of patients with nodular regenerative hyperplasia revealed that various shunting procedures are generally recommended. After the failure of medical management in patients with nodular regenerative hyperplasia, portosystemic shunting may be indicated before proceeding to hepatic transplantation.

Adult↗

Ischemia-reperfusion injury of the spinal cord: protective effect of the hydroxyl radical scavenger dimethylthiourea.

PURPOSE: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both. METHODS: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination. RESULTS: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (10/11) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10). CONCLUSIONS: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits.

Animals↗

Is breast preservation possible in women with large, locally advanced breast cancers?

Breast conservation therapy is an accepted treatment option for early stage breast carcinoma, but is rarely considered appropriate for locally advanced nonmetastatic lesions. Mastectomy specimens of 46/50 patients treated at the Ochsner Clinic and the Mallinckrodt Institute of Radiology with neoadjuvant chemotherapy prior to mastectomy +/- irradiation were evaluated by a single pathologist to assess tumor response to chemotherapy. Forty percent of this group would potentially have been eligible for breast conservation therapy, using a residual tumor size of < or = 4 cm with negative surgical margins as the criteria. Patients most likely to qualify for breast conservation therapy were those with T3N0-1 lesions (67%). Least likely were patients with skin involvement at diagnosis 4/33 (12%). Tumors with an extensive intraductal component at biopsy often had residual islands of intraductal carcinoma occupying the original tumor volume, even when the invasive component was absent or much reduced. A prospective trial will be required to determine whether or not acceptable local control rates can be obtained after breast conservation therapy for that subset of patients with a favorable response to induction chemotherapy.

Adult↗

The value of flow cytometric analysis in multicentric glomus tumors of the head and neck.

Glomus tumors of the head and neck include those arising from the carotid body, jugular vein, and vagus nerve. Because these cannot be differentiated histologically, when encountering a large tumor mass involving more than one structure in the carotid sheath, one often cannot be sure whether the tumors are from one or more of these structures. The authors performed DNA flow cytometric analysis on a patient with a multicentric glomus tumor on the right side of the neck involving the carotid body, jugular vein, and vagus nerve, in an effort to determine the separate or similar origin of her tumor mass. Different DNA indices, including a double peak for the carotid body tumor, were obtained. There were three aneuploid tumors and one diploid tumor (DNA indices: carotid body 1.78, 2.04; jugular vein 2.20; vagus nerve 1.82). Different synthetic phase fractions were calculated for each aneuploid tumor except the second carotid body peak (carotid body 7.2; jugular vein 3.6; vagus nerve 4.8). The authors conclude that DNA flow cytometry may be useful in confirming the multicentric origin of tumors that encompass more than one histologically similar structure.

Adult↗

Improved survival after pulmonary resection of metastatic colorectal carcinoma.

While hepatic resection of metastatic colorectal carcinoma is accepted as effective in selected patients, resection of metastases to other solid organs has not gained wide acceptance. We retrospectively reviewed the records of 49 patients who had resection of isolated pulmonary (18 patients) and hepatic (31 patients) metastases from the large bowel, comparing disease-free survival and overall survival. Tumor parameters analyzed included Dukes' stage, deoxyribonucleic acid (DNA) flow cytometry, and number of metastases. Dukes' B and diploid tumors had longer disease-free survival and overall survival than did Dukes' C and aneuploid tumors, though the difference was not significant. Patients with a single lung metastasis had a significantly longer disease-free survival (P = .02) than did patients with multiple metastases. Mean and median survival were longer in patients with lung metastases. Five-year actuarial survival was 19% for patients with liver metastases and 47% for patients with lung metastases. Resection of isolated pulmonary metastases from the large intestine results in survival comparable to or better than resection of hepatic metastases. An aggressive surgical approach is warranted in patients with isolated resectable pulmonary metastases of colorectal carcinoma.

Actuarial Analysis↗

Wilms' tumor with metastasis to the left testis.

Wilms' tumors account for the vast majority of renal neoplasms in infants and children. Common areas for metastases include the lung, liver, and contralateral kidney. Less common sites include the bone, skin, brain, and orbit. We report a case of Wilms' tumor in a 13-month-old boy who, after radical left nephrectomy, developed a left testicular mass that turned out to be metastatic Wilms' tumor. The epidemiology, case history, review of the literature, and possible etiology of this rare site of metastatic Wilms' tumor are discussed.

Combined Modality Therapy↗

Is limb-sparing surgery applicable to neurogenic sarcomas of the extremities?

The presentation, treatment, and outcome of 12 patients with high-grade neurogenic sarcoma (NS) of the extremity were compared with those of 21 patients with high-grade extremity soft-tissue sarcoma of nonneural origin in a retrospective study from January 1976 to January 1988. Pain and neurologic deficit were more common in the NS group. Limb-sparing surgery was carried out with equal frequency in both groups. Local recurrence was six times more frequent in the NS group at three-year follow-up (59% vs 10%). Width of resection margin was the dominant prognostic variable bearing on local control after limb-sparing surgery. Anatomic and functional constraints tended to limit resection margin in patients with NS arising from mixed motor-sensory or predominantly motor nerves.

Adult↗

Myosarcomas of the small and large intestine: a clinicopathologic study.

A retrospective study was made of 38 myosarcomas of the small and large intestines (34 leiomyosarcomas and 4 malignant leiomyoblastomas). Endoenteric, small, and noninvasive tumors were successfully treated by simple wedge excision, cautery snare removal, or segmental bowel resection with a high 5-yr cure rate of 86% (12/14). Exo-enteric tumors often invaded adjacent structures or perforated into the peritoneal cavity. Extensive resection procedures, including pancreaticoduodenectomy, abdominoperineal resection, and pelvic exenteration salvaged only 13% (2/16) of these patients. Three clinicopathologic factors adversely affected prognosis: i) tumor size greater than 5 cm in diameter, ii) extra-intestinal invasion or free perforation, and iii) high histopathologic grade of malignancy. The presence of none, one, two, or three of these adverse factors gave decreasing 5-yr survival rates of 100, 44, 31, and 0%, respectively. These observations suggest use of a multimodal treatment program that may minimize treatment failure from local as well as distant disease.

Adolescent↗

Myosarcomas of the stomach: natural history, prognostic factors and management.

A retrospective study was made of 41 patients treated for gastric myosarcoma to identify prognostic factors that influence results. The adjusted five- and ten-year survival rates were 56% and 43% respectively, with no significant difference between leiomyosarcoma and malignant leiomyoblastoma. A histopathologic grade of malignancy could be assigned to each tumor according to the degree of hypercellularity, nuclear abnormality, mitotic rate and other characteristics. High histopathologic grade, large tumor size (greater than 5 cm diameter) and invasion of adjacent organs adversely affected prognosis. Five-year survival after curative treatment was: 100% (9/9) for small tumors, of which six were treated by wedge gastric resection; 67% (8/12) for large tumors, mostly after subtotal gastrectomy; and 0% for tumors that invaded adjacent organs, despite extended resections. It is concluded that the management of gastric myosarcomas can be planned according to these prognostic factors and that multimodal therapy of tumors with adverse factors warrants consideration.

Adult↗

Anorectal melanoma.

Primary malignant melanoma of the anorectum is a rare and virulent malignancy associated with an extremely poor prognosis in spite of aggressive initial therapy. Fifty-one patients with this disease were treated at Memorial Sloan-Kettering Cancer Center during the last 50 years and only six (12%) survived five years. This report views in detail 36 of the patients treated since 1950. In this group there was a female predominance (21 females, 15 males), and median age was in the 6th decade (range 27-75). Common presenting symptoms were pain, bleeding, mass or "hemorrhoids" of 1-12 months duration. In two-thirds, of the cases, a radical surgical approach was attempted. Other therapy included local excision alone or combined with groin dissection, local excision followed by delayed rectal resection and local tumor destruction by cryosurgery or fulguration. Mean survival was 21.5 months. Three patients had palliative treatment only with radiation therapy. Histopathologic study of 30 lesions showed that two-thirds were bulky or polypoid lesions and two-thirds showed junctional changes. The virulent prognosis of primary anorectal melanoma appears directly related to tumor size and thickness. Although all four of the five-year survivors had radical surgery, the three whose tumors could be measured had superficial lesions. In general, curative efforts by radical surgery were no more effective than local treatment by excision or cryosurgery. One patient, however, did have a thin lesion but also had nodal metastases and survived over five years after radical surgery. Although these data suggest that radical resection may cure patients with lesions thinner than 3 mm, it does not exclude the possibility that local excision might also be curative. For larger lesions that have not been cured by radical surgery, more conservative local approaches by excision or cryotherapy might be the optimum way of achieving local palliation.

Adult↗

Epidemiology of breast carcinoma: Age, menstrual status, and exogenous hormone usage in patients with lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) of the breast is a neoplastic condition associated with premenopausal women and it is largely for this reason that LCIS has been considered to be an estrogen-dependent lesion. In this report we present the results of a study of age at diagnosis, menstrual status, and exogenous hormone usage in 59 women with LCIS and in 190 patients with duct carcinoma. When LCIS was associated with duct carcinoma, 46% of patients were postmenopausal and in the group that also had infiltrating lobular carcinoma 71% were postmenopausal. Nine of 39 (23%) patients whose only carcinoma was LCIS were postmenopausal, 56% were premenopausal and 21% were menopausal. Seven of the nine postmenopausal women had never used a hormone-containing medication. In a comparison group with only duct carcinoma, 59.4% were postmenopausal and 35.2% had taken a hormone preparation. The high proportion of postmenopausal patients with LCIS leaves considerable doubt as to whether all lesions termed LCIS are equally dependent on estrogens at all stages in their evolution. We found no evidence to link LCIS with exogenous hormone usage in postmenopausal women. Prospective studies of hormone levels in patients with LCIS and in their relatives may provide an explanation for persistence of the lesion in postmenopausal women and could aid in identifying women at risk of developing invasive carcinoma.

Adult↗

Nervous system involvement in type IV glycogenosis.

A 30-month-old girl exhibited the 19th known case of type IV glycogenosis. Extensive involvement of the nervous system was found at autopsy. This represents only the second patient in whom the fine structure of the CNS and skeletal muscle has been described. We have also identified the abnormal polysaccharide in peripheral nerve, a finding that, to our knowledge, has not been reported previously. Our review of the literature indicates that approximately 50% of these patients exhibit signs or symptoms referable to the neuromuscular system. Most clinical and pathologic studies have focused on the severe liver involvement; insufficient attention has been directed toward the nervous system. This emphasizes the need for more detailed neurologic and neuropathologic examinations of children with type IV glycogenosis.

Age Factors↗