Henry F. Sears

Granulocytic sarcoma. Local presentation of a systemic disease

The case of a pregnant woman with a breast mass that proved to be a granulocytic sarcoma is presented. Her systemic therapy was initiated at a time when her tumor burden was possibly relatively low and a good response to the aggressive combination chemotherapy including Daunomycin was obtained. She was successfully carried through pregnancy and delivered a normal child despite combination chemotherapy. Factors relating to her case have been reviewed in the literature.

Clinical and immunologic studies of disseminated BCG infection.

Eight patients with disseminated BCG infection following injection of BCG into primary melanomas have been studied. These patients developed persistent fevers beginning 9 to 20 days following BCG injection. Severe liver function abnormalities occurred in all patients and peaked approximately 20 days following BCG injection. The persistent fevers, and clinical signs and symptoms of disseminated BCG infection lasted from 7 to 22 days before subsiding. Liver function abnormalities sometimes took six months to return to normal. Evidence of granulomas in liver and bone marrow were present. The natural course of this disease did not appear to be affected by therapy with isoniazid (INH). In vitro immunologic studies revealed a severe depression of lymphocyte reactivity in five of six patients sequentially tested. Wide dissemination of BCG from the site of injection is a severe complication of BCG therapy. The clinical course of this disease and suggestions for management are described in this paper.

Analysis of staging and management of patients with sarcoma: a ten-year experience.

Over ten years, 70 patients with soft tissue sarcoma were treated for their primary tumors at the hospital of The Fox Chase Cancer Center. The clinical characteristics of these tumors are correlated with the outcome of various management efforts. The results of these evaluations identify three groups that can provide the basis for future treatment decisions and stratification for randomized studies of management options. The first group of patients, those with small well differentiated tumors, have no systemic spread regardless of the treatment modality used. The second group, those with large (>5 cm) tumors that are moderately or poorly differentiated, do uniformly poorly despite the management techniques used. An intermediate group, those with high grade or large size but not both, have outcomes which may be corrected to treatment modalities.

Initial clinical evaluation of two murine IgG2a monoclonal antibodies for immunotherapy of gastrointestinal carcinoma.

Eleven patients with advanced gastrointestinal (GI) carcinoma were entered in Phase I initial clinical trials with IgG2a anti-GI carcinoma monoclonal antibodies (MAbs) GA733 (five patients) or CO19–9 (six patients). Infusion of MAb GA733 in doses > 30 mg was accompanied by mild and short-lasting GI toxicity. Infused MAb GA733 was bound to each patients tumor tissue in vivo. MAb circulated in the blood for 10–25 days. All patients developed anti-mouse antibodies between 15 and 60 days post infusion. Furthermore, all but one patient raised anti-idiotypic antibodies against MAb GA733.Following administration of 10–600 mg of MAb CO19–9, no immediate or delayed toxicity symptoms were noted. Binding of infused MAb CO19–9 to tumor cells in vivo could not be detected in any of the six patients studied. The MAb circulated in the bloodstream between 5 and 12 days. Human anti-mouse antibody was detected in sera of three patients.None of the eleven patients treated with either MAb had anti-tumor responses in this Phase I clinical trial. The strong binding reactivity of MAb GA733 to tumors in vivo suggests the use of this MAb in cancer patients with less tumor burden to determine the tumoricidal efficacy of this antibody.

Postoperative Management of Patients with Pheochromocytoma

The optimal preoperative and postoperative management of patients with pheochromocytoma demands a multidisciplinary approach. We report on 5 recent patients to illustrate the large volumes of fluid needed in the early postoperative period. This large fluid requirement is owing to a combination of a change in vascular compliance after excision of a pheochromocytoma, the residual effects of specific preoperative medications (phenoxybenzamine and alpha-methyl-p-tyrosine) and the loss of fluid into the retroperitoneal compartment (third space) produced by extensive dissection. It takes 3 half-lives (36 hours) to dissipate the effects of phenoxybenzamine and alpha-methyl-p-tyrosine, which corresponds to the time in which these patients require large volumes of intravenous fluids.

Experimental cryopreservation and autotransplantation of parathyroid glands: technique and demonstration of function.

A canine model for cryopreservation and autotransplantation of parathyroid glands was developed as a prototype for cryopreservation of human parathyroid glands. Each of 18 dogs had two parathyroids removed, sectioned, and cooled at a controlled rate to −80° in media containing 10% dimethylsulfoxide and 10% autologous serum. After storage for two months at −196° the tissue was thawed and implanted in muscle; the remaining two parathyroid glands were removed from the neck. Function was assessed by monitoring serum calcium levels and measuring parathyroid hormone levels in venous effluent from the graft beds. Autograft function was demonstrated in ten of 18 dogs; graft failure occurred in four dogs. In the remaining four dogs, function could not be evaluated because of accessory parathyroid tissue. Parathyroid tissue cryopreserved for nine months was documented to function in six of seven dogs. Histologic study of the cryopreserved, autografted tissue showed normal parathyroid architecture.

Circulating tumor markers and assessment of response to intrahepatic chemotherapy of colon carcinoma.

TO ASSESS THE CHANGE IN CONCENTRATIONS of circulating gastrointestinal cancer-associated antigens in response to therapy, we analyzed the sera of patients with hepatic metastasis from colorectal carcinoma who were treated with intrahepatic arterial chemotherapy. Serial serum samples were assessed for the tumor-associated antigens, carcinoembryonic antigen (CEA) and the gastrointestinal cancer antigen CA 19–9. Computed axial tomographic (CAT) scans were made to assess the size of the hepatic metastasis. In 9/10 of these patients the CEA predicted tumor response within 2–6 weeks after initiation of treatment, and in 7/10 the information was supported or more dramatically demonstrated by the CA 19–9. Combining data from both tumor markers may provide a more accurate assessment of the clinical response than one antigen alone. Recurrence of hepatic metastatic growth or extrahepatic tumor also was identified by elevation of one or both circulating tumor-associated antigens prior to other laboratory or clinical evidence of tumor growth.

Complication with mechanical stapling device in creation of ileoconduit.

Of 296 patients with pelvic malignancy and ileal urinary conduits, urinary tract calculi developed in 14. Calculi which ordinarily require surgical intervention because of their size may pass spontaneously in patients with ileoconduits because of the presence of a chronically dilated colllecting system and the surgical elimination of three of the four sites of stone impaction (pelvic brim, ureterovesical junction, and ureteral orifice). In 1 patient multiple calculi developed around the surgical staples used to create the proximal end of the ileal conduit. We recommend that autosuture with stapling devices not be used to create the proximal end of an ileal urinary conduit.

Cryopreserved lymphocytes: Decreased response in immune assays of a population of sarcoma patients

In vitro assays of cellular immunity in cancer patients are hampered by a number of variables because of the required cell culture and isotope counting. One method of overcoming some of these technical difficulties is to store test and reference materials. Cryopreservation of lymphocytes from normal volunteers and certain cancer patients has been shown to preserve normal cell function in these in vitro assays for up to 1 year (25, 27, 28). Frozen immunocompetent cells have also been used to identify significant changes in lymphocyte function associated with BCG therapy 65). Our studies of patients with cancer have demonstrated a population of cancer patients, those undergoing radiation therapy, in whom frozen cells do not react in stimulation assays in the same way as fresh cells from the same patient. These patients are often the same ones for whom FicollHypaque gradient separation of mononuclear cells is difficult. To evaluate this phenomenon, simultaneous cultures and stimulations with PHA were performed using both fresh and frozen mononuclear cells from three groups of patients with sarcoma, and one normal volunteer population. These results were compared.

Parathyroid autotransplantation: Use of cryopreserved glands in an investigation of hypocalcemia

Abstract Parathyroid glands were removed from 12 dogs, cryopreserved, and autotransplanted: one-half of these dogs were made eucalcemic with 1,25-(OH) 2 -cholecalciferol during the peritransplant period while the other dogs were allowed to become hypocalcemic. The interval of hypocalcemia did not aid in autograft function success. Cryopreserved autotransplanted parathyroid glands can maintain calcium homeostasis in the dog.