Efficacy of domperidone gel in an induced model of fescue toxicosis in periparturient mares.

The objective was to evaluate the efficacy of domperidone in the prevention of reproductive complications of fescue toxicosis in periparturient mares. Pregnant mares at ≤310 days of gestation were fed ≥200 µg ergovaline per kg diet daily in endophyte-infected fescue hay and seed, starting ≥30 days before their expected foaling date (EFD: 340 days after breeding). Thirty-five mares were randomized to a treatment group to receive either domperidone gel (n = 20, 1.1 mg/kg, PO, once daily) or placebo (n = 15). Treatment was initiated 10 to 15 days before the EFD and continued for 5 days after foaling. "Treatment success" was defined as foaling within 14 days of the EFD, adequate mammary development on the day of foaling, and adequate lactation for 5 days postpartum. Twenty-seven mares were included in the effectiveness analysis. More mares in the domperidone group (12/13, P < 0.0001) were treatment successes than in the control group (1/14). Gestation length was shorter (P = 0.0011), and lactation at foaling (P = 0.0011) was better for the domperidone-group mares. Foals from two control mares were born dead and four others died or were euthanized within a few days after birth, compared with one foal death (an autolyzed twin) from a domperidone-treated mare. Plasma IgG concentrations were evaluated in 24 foals. Failure of passive transfer of immunoglobulins (IgG <800 mg/dL) occurred in 13/16 (81%) foals of domperidone-group mares and 7/8 (88%) foals of control mares. In conclusion, the reproductive complications of fescue toxicosis in periparturient mares induced by a fescue seed/hay model were prevented by treatment with domperidone.

Soft part sarcomas of the head and neck.

During the 28-yr-period from 1949-1977, 285 patients with sarcoma of the head and neck region were seen and treated at Memorial Cancer Center. Two hundred forty-two cases were determinate, and none was lost to follow-up study. The determinate and absolute 5-yr cure rate was 32%. More than 50% of the cases were seen in children (8 cases were congenital) and were almost universally anaplastic and prone to generalized metastasis with fatal outcome. Combined modalities of radical surgery, postoperative radiotherapy, and chemotherapy over a prolonged period have markedly altered the prognosis of these tumors. Soft part sarcomas are an unusual group of tumors with a common fibrosarcomatous background. The qualified pathologist can identify quite accurately the different histologic entities and their varying grade, a point of great significance as to clinical course and treatment.

Epidermoid carcinoma of the mouth and pharynx at Memorial Sloan-Kettering Cancer Center, 1965 to 1969.

One thousand thirty-four cases of epidermoid carcinoma of the mouth and pharynx were seen by the Head and Neck Service of Memorial Hospital during a recent 5 year period, 1965 to 1969. The 656 determinate cases previously untreated offer a clear basis for evaluation of the 5 year results of treatment, which as surgical in 90 percent of the cases. Preoperative radiotherapy was used in 130 cases. Preoperative radiotherapy was used in 130 cases, matched with 126 untreated cases. Etiologic factors are discussed. The presence and degree of lymph node metastasis are of paramount significance. Indications for elective treatment of the clinically negative neck are discussed in terms of anatomic, logistic and statistical principles. An analysis of failure point toward a continuing effort at combined therapy in this regional disease.

Carotid body tumors: a 40-year study.

A total of 44 carotid body tumors were observed for over 40 years at Memorial Sloan-Kettering Cancer Center in New York. The true nature of th paraganglioma can remain obscure in those patients without prior tissue biopsy or sophisticated diagnostic studies. Eighteen patients came to surgery without a primary working diagnosis of the conditions, 43 percent of the seris. Significant advances in the preoperative workup of a cervical mass attached to the carotid sheath are now recommended: ultrasonography, radioisotope perfusion scanning, and selective carotid arteriography. Catecholamine determination should be considered for any paraganglioma exhibiting vasomotor instability or hypertension. Prior to 1945 the carotid bifurcation was sacrificed eight times with a 50 percent mortality occurring in relatively youthful subjects. In the 35 years since then, a more sophisticated surgical technique preserving the carotid circulation has resulted in over 30 resections with but one fatality. Multicentricity, both in the sporadic and the familial form, is characteristic of this rare tumor, also called "APUDoma." (APUD is an acronym derived from three of the most important characteristics of these cells: a high amine content, amine precursor uptake, and decarboxylation. Its malignant potential is beyond debate.

cis-Dichlorodiammineplatinum(II)-based chemotherapy as initial treatment of advanced head and neck cancer.

During the past 2--3 years, a total of 73 patients with advanced head and neck cancer (mostly stage IV) were treated with cis-dichlorodiammineplatinum(II) (cis-platinum) as initial therapy, either alone or in combination with other agents. After chemotherapy, the patients received surgery and/or radiation therapy in standard fashion. Major degrees of tumor regression were seen in 40%--71% of the patients. cis-Platinum and bleomycin given by infusion gave the highest response rate (71%). The addition of high-dose methotrexate to cis-platinum plus bleomycin produced an unacceptable level of toxicity. Similarly, a four-drug regimen in which low-dose methotrexate and vinblastine were added to cis-platinum and bleomycin resulted in increased toxicity without additional therapeutic effect. Initial chemotherapy does not compromise subsequent surgery or increase either the immediate complications of surgery or the acute toxicity of radiation therapy. It seems unlikely that initial chemotherapy has altered the grim prognosis of an advanced, inoperable presentation. The effect of initial chemotherapy on advanced, operable disease will have to be assessed by suitable controlled trials.

Paragangliomas of the head and neck region: a clinical study of 69 patients.

Over a 38-year-period 73 paragangliomas from the head and neck region were seen at Memorial Hospital. These occurred in 69 patients. There were 44 carotid body, 13 vagal body, eight jugulo-tympanic, and three nasal paragangliomas. In addition, one each arose in the orbit, larynx, and area of the aortic arch. Sixty-two patients were surgically treated while three received irradiation only and four were observed but not treated. Follow-up was obtained for 94% of the patients. There were six postoperative deaths, five of which occurred before 1945. Of those treated surgically, 37 had no evidence of recurrent tumor while the paragangliomas recurred locally in 11. All patients in the radiation and untreated groups had persistent tumor. Malignant behavior with death due to tumor was observed in five cases (four carotid body and one vagal body paraganglioma). Using modern techniques carotid body and vagal body paragangliomas can usually be managed by surgery alone. Other paragangliomas of the head and neck due to their anatomic location are sometimes best treated by a combination of surgery and radiation or only by radiation therapy.

Carcinoma of the oral cavity. factors affecting treatment failure at the primary site and neck.

A retrospective review of the clinical records of patients with carcinoma of the oral cavity was undertaken, and several parameters were studied in terms of comparing two groups of patients: those who were controlled at the primary site and neck and others who failed locally or regionally following initial treatment. A comparative statistical analysis of the factors studied revealed that female patients who had a higher T status, a higher N status, and thus a higher stage of disease did poorly in terms of local and regional control of disease. Those patients whose primary tumors manifested deep invasion and those who had positive margins after surgical resection at the primary site had also a significantly high incidence of local/regional failure. Presence of extracapsular extension of disease in cervical lymph nodes and involvement of soft tissues in the neck as well as involvement of multiple lymph nodes at multiple levels also put the patients in a high risk category. We urge that these factors be considered as prognostic criteria and be used to select patients for treatment by additional modalities on an elective basis in hope of achieving better local and regional control of disease and perhaps better cure rates.

Immediate repair of the Commando defect by cervical and pectoral flaps.

A ten year experience with immediate cervical flap repair of the Commando defect is reported in a selected series of more than seventy patients with clinically negative neck-nodes. Preoperative radiotherapy of 2"000 and 3,000 r to the neck and primary tumor has not interfered with wound healing. The cosmetic and functional result is highly commendable.

The prediction of lymph node metastases from oral squamous carcinoma.

In an attempt to predict which cases of oral and oropharyngeal squamous carcinoma are likely to metastasize to regional lymph nodes a series of 898 cases was grouped according to site, size, grade of histological differentiation, and presence or absence of histologically confirmed regional lymph node metastases. The results were analysed by a logistic multiple regression analysis. They showed that the sites may be divided into three clusters, Cluster 1 consists of tumors of lip, floor of mouth, cheek mucosa, hard palate, and gingiva. These are not significantly different as regards metastasis rate. Cluster 2 consists of tumors of the anterior two-thirds of tongue and has a higher tendency to metastasis than those in Cluster 1. Lesions of the posterior third of tongue and oropharynx form Cluster 3 which exhibits the greatest tendency to metastasis. Sizes of primary lesions are clustered in groups of lesions less than 3 cm, those 3 to less than 4 cm, and those 4 cm or larger, in ascending tendency to metastasis. Well-differentiated and moderately differentiated tumors are not significantly different in their tendency to metastasize and may be reduced to a single cluster, whereas poorly differentiated tumors have a markedly higher metastasis rate. Using these clusters it has been possible to predict the logistically transformed probability of metastasis to a high degree of accuracy (R=0.9398). From this we conclude that if for a given tumor we know to which site, size or differentiation cluster it belongs, we can then estimate its probability of metastasising.