A simple method for obtaining peritoneal macrophages from chickens.

A simple technique for inducing the production of peritoneal exudate cells within 3 to 4 days in chickens is described. In each 5 to 6 week old chicken, 5 to 8 ml of washed Sephadex particles suspension in saline (3%) were injected intraperitoneally. Three to 4 days later, peritoneal exudate cells were harvested, washed, suspended in Hank's solution, counted and adjusted to one million cells per ml. In each well of 4-chamber slide 1 ml of peritoneal cell suspension was incubated at 37 degrees C for 30 min. Cultures were then gently washed several times leaving a monolayer of glass adherent cells. The phagocytic activity of these adherent cells was examined using either latex particles or antibody-sensitized sheep erythrocytes. The monolayer cells were incubated with particles in Hank's solution (with excess particles in particle/peritoneal cell ratio) for 1 h at 37 degrees C. From 99.5 to 100% of the monolayer cells were found actively phagocytic for either the latex particles or sensitized erythrocytes or both. Adherent cell monolayers were cultivated in vitro for several weeks with no detectable decrease in their phagocytic activity.

Repair of abdominal and thoracic wall defects by bovine fascia (ox fascia).

Sheets of heterologous fascia (bovine fascia) were used to close large defects of the thoracic and abdominal wall in four patients with malignant neoplasms. The material was well tolerated by the body and provided adequate protection and support to the underlying viscera. Although the fascial graft was not covered by skin flaps in two patients with abdominal wall defects, it became readily incorporated into granulation tissue that was receptive to split thickness skin grafts. The fascia was used successfully in a contaminated field and control of active infection was possible without removing the graft. These findings demonstrate that heterologous fascia is particularly useful under conditions that are not suitable for the use of synthetic materials.

Effectiveness of systemic BCG therapy in advanced melanoma.

The effect of systemic BCG therapy on advanced melanoma was studied in 42 patients with stage II and stage III disease. Evaluation of the immune response prior and during therapy revealed that patients who failed to convert a negative purified protein derivative (PPD) reaction and those having a low stimulation ratio of lymphocyte cultures had rapidly progressive disease and short survival. Neither tumor regression nor prolongation of survival could be appreciated in patients with stage III disease. Furthermore, aggravation of symptoms was observed in patients with visceral metastases. Fifty percent of the patients with stage II melanoma treated by operation and adjuvant immunotherapy had recurrent or metastatis disease within two years. No adverse effects were noted in patients with early disease who received adjuvant therapy. Two patients who had a full course of systemic BCG therapy developed severe reactions after intralesional injection of the vaccine. Further experience with various immunotherapeutic regimens and longer follow-up are necessary to evaluate its value in the early stages of melanoma.

Intermittent occlusion of the hepatic artery and infusion chemotherapy for carcinoma of the liver.

Twenty-nine patients with hepatocellular or metastatic colon carcinoma were included in the present study. A system of staging the extent of disease was developed to provide a guideline for patient selection and evaluation of the results of therapy. Sixteen patients received intraarterial infusion chemotherapy only and thirteen were treated by a combination of intermittent occlusion of the hepatic artery and infusion chemotherapy. In this latter group intermittent occlusion of the hepatic artery was employed as an alternative to hepatic artery ligation. Patients in either group having disease confined to the liver experienced good response to treatment, had a low incidence of drug-related complications, and survived for relatively long periods. The study confirmed that intermittent occlusion of the hepatic artery is a safe procedure and that it is not accompanied by an increase in morbidity or mortality. The rationale for using this technic and the advantages it has over hepatic artery ligation were presented. The procedure is currently being utilized with increasing frequency in patients in relatively early stages of the disease. Accumulation of more material and longer periods of follow-up are required to determine the therapeutic advantages of the new method over infusion chemotherapy alone.

Immune response and non-specific immunotherapy in melanoma.

Tumour-associated antigens and specific immune response to these antigens have been clearly demonstrated in patients with melanoma. Impaired cellular immune reactions are evident in patients with progressive and disseminated disease. Immunotherapy is used to heighten the host resistance and hence prevent recurrence and spread of the tumour. BCG vaccine has been used to produce nonspecific stimulation of the immune system. Preliminary evaluation of the effect of adjuvant systemic BCG therapy suggests that the treatment may have a beneficial effect on patients with early melanoma.

Treatment of hepatic metastases in cancer of the colon and rectum. A preliminary report.

Treatment of hepatic metastases in 31 patients with cancer of the colon and rectum consisted of wedge resection or partial hepatectomy in 2; systemic chemotherapy in 13; chemotherapy infusion of the hepatic artery in 9; and chemotherapy infusion combined with intermittent arterial occlusion in 7. Patients were not randomized with regard to type of treatment, yet the age and sex distribution of these patients was similar in the three groups receiving chemotherapy. One patient treated by resection of a solitary hepatic lesion had been living with no evidence of disease for over three years. None of the patients who received systemic chemotherapy exhibited evidence of objective response. Four of 9 patients who received chemotherapy infusion and 4 of 7 who received a combination of arterial occlusion and chemotherapy infusion survived for periods ranging from 18 to 32 months. Clinical evaluation of individual patients indicated that those having metastases confined to the liver (Stages II and III) who received intermittent arterial occlusion and chemotherapy infusion enjoyed longer periods of objective response and experienced fewer complications than did those treated by chemotherapy infusion alone.

Midline cancer of the floor of the mouth: role of suprahyoid dissection.

Of 37 patients with squamous cell carcinoma of the floor of the mouth seen during a 5-year period, 28 were treated primarily by surgery. Ten of the 28 patients presented with midline cancers measuring between 1.0 and 3 cm (T1 and T2). Three of these patients had local excision only. Metastases to the submandibular lymph nodes later occurred in 1 of these 3 patients. The remaining 7 patients with midline lesions had wide excision of the tumour, marginal resection of the mandible and bilateral suprahyoid node dissection. Of these 7 patients 4 remained free of disease for periods ranging between 2 and 5 years. Two of these had lymph node metastases. These results suggest that en bloc excision of relatively small midline cancers (i.e. not exceeding 2 cm (T1) in largest diameter) with bilateral suprahoid node dissection gives effective control of these lesions.

A method of intermittent occlusion and chemotherapy infusion of the hepatic artery.

A method of intermittent occlusion of the hepatic artery and chemotherapy infusion has been developed using a catheter introduced into the hepatic artery, with interruption of the blood flow accomplished by inflation of the balloon. This method is less likely than ligation of the hepatic artery to produce massive liver necrosis, and it ensures adequate perfusion of the tumor tissue with the chemotherapeutic agents.

Effect of infusion chemotherapy and hepatic artery ligation on normal liver: experimental study in the cat.

The effects of arterial infusion with chemotherapy alone or in combination with hepatic artery ligation on the normal liver of the cat were studied. Early in the course of treatment cats receiving chemotherapy infusion only appeared sicker than animals in other groups. Yet only 1 of 5 cats was dead at 12 weeks. In contrast, 4 of 6 animals that had hepatic artery ligation and chemotherapy infusion, and 3 of 6 that had ligation of the hepatic artery only, died during the same period of follow-up. Progressive liver damage after dearterialization accounted for the high mortality rate. Histologic examination of liver biopsies taken from animals in these latter groups revealed marked destruction of the parenchyma. These changes were more extensive in animals treated by a combination of hepatic artery ligation and chemotherapy infusion. To avoid the injurious effects of permanent interruption of the hepatic arterial flow on normal liver tissue an alternative method of hepatic dearterialization is currently under investigation.

Role of preoperative bone scan in carcinoma of the breast.

Although a skeletal scan is an effective means of detecting early metastatic deposits from carcinoma of the breast, its indiscriminate use in screening patients with early tumors does not seem justified because of the low yield of abnormal results. Selection of patients for this procedure should be based on the size of the tumor and the clinical stage of the disease. It is extremely unlikely that patients with a T1 lesion will have an abnormal skeletal scan. A preoperative scan in indicated for T2 lesions in patients with a central or medial quadrant mass, inflammatory carcinoma, palpable axillary lymph nodes or other clinical evidence suggestive of spread beyond breast tissue. All patients with T3 and inoperable tumors should have a bone scan prior to therapy to define the extent of the disease. A routine postoperative scan at six month intervals may be considered only in patients with large primary lesions and involvement of regional lymph nodes.

The influence of pineal ablation and administration of melatonin on growth and spread of hamster melanoma.

Removal of the pineal organ resulted in increase in the growth of transplanted melanoma in hamsters. Administration of melatonin, which is the priniciple indole found in pineal tissue, to pinealectomized animals abolished this effect. Therefore it was concluded that the effect of pinealectomy on tumor growth is due to a lack of endogenous melatonin. Administration of large doses of melatonin (4 mg/day) to intact animals, however, did not influence the rate of tumour growth, indicating that the drug has no direct effect on tumor growth and that the changes produced by melatonin deficiency is perhaps due to complex reaction involving centers in the hypothalamus and brain stem. Certain morphologic changes were noted in the pineal organs of animals treated with exogenous melatonin. Although the biologic significance of these changes is not clear, study of the electron micrographs indicates that the pinealocytes of the melatonin-treated animals are in a state of increased activity.

Effect of alkali metal salts on Sarcoma I in A/J mice.

The chloride salts of lithium (Li+) and cesium (Cs+) were evaluated for their ability to influence the growth of Sarcoma I implants in A/J mice. The administration of daily doses of either 1 or 3 mEq/kg CsCl to these mice reduced the incidence and size of tumor implants. This effect was not apparent in animals receiving a smaller dose (0.5 mEq/kg) of the same drug. At the time of sacrifice the serum level of Cs+ in this latter group was approximately half that recorded in animals receiving the higher doses of CsCl. No effect on tumor incidence or rate of growth was observed in animals receiving different doses of LiCl. Because of the similarities that existed between cesium and potassium, it was postulated that the effect of cesium was due to alterations in the intracellular composition of the tumor cells. Also, the possible role of cytotoxic agents in potentiating the inhibitory effect of cesium on tumors was discussed.

Inhibition of melanoma growth in hamsters by type-2 adenovirus.

Type-2 adenovirus was shown to inhibit the growth of transplantable hamster melanoma in 70% of Syrian hamsters without any injurious effect to the host. Greatest inhibition of tumor formation was seen when animals were injected with 10(6) TCD50 of adenovirus and 2.5 x 10(5) tumor cells, or 10(6) TCD50 of virus and 5.0 x 10(5) tumor cells followed either 1 or 7 days later by a second injection of a similar dose of virus. Significant inhibition in tumor growth was also noted when 2 injections of virus (10(6.2) TCD50/injection) were given on 2 separate occasions as late as 7 and 10 days after the inoculation of tumor cells. The mechanism of tumor inhibition is not known but it could be due to a combination of factors such as viral toxicity, viral oncolysis, and antitumor immunity.