Resistance of Thyroparathyroidectomized Rats to Growth of a Spindle-Cell Sarcoma

Abstract

The published reports on the effect of thyroidectomy on neoplastic growth present divergent opinions. Rohdenburg, Bullock and Johnston in a series of 29 thyroidectomized rats found at 40 days after inoculation with Flexner-Jobling carcinoma 52% of “cures” against only 16% of regressions in the control group. Recently Bischoff and Maxwell inoculated 13 thyroparathyroidectomized rats with rat carcinoma 256. Based on a comparison with 16 inoculated litter-mate controls they observed “no significant difference in percentage of takes, rate of tumor growth, or final mortality”. Our tumor, a sarcoma, which arose spontaneously in a rat uterus has been transplanted during the past three years into more than 1000 rats. Successfully inoculated tumors in normal rats have not been seen to regress. This is mentioned to indicate that a spontaneous regression of this tumor, if it does occur, is uncommon. The operation consists of complete ablation of thyroid and parathyroid glands. All rats were from our colony of Wistar Institute albino stock. All individuals of the litters, or groups, were inoculated bilaterally into groin pockets from the same tumor and at the same time. In Table I where the tabulation is by litters the 4 longest post-thyroidectomy ones (1, 2, 3, 4) are placed first. Of the 18 successful takes in this group 14 completely regressed. This high percentage (77%) of regressions in a group where the shortest post-thyroidectomy period was 112 days is in contrast with 25% of regressions in all successfully inoculated remaining rats with shorter post-operative periods. In both groups it is seen that a first inoculation may fail and a second one succeed. This is true also for normal control animals, and sometimes may result from the accidental introduction of bacteria into the pocket. In the rats with relatively short post-thyroidectomy periods there is an usual tendency for the second inoculation tumors to regress. This may be explained in whole or in part by the fact that an average of 20 days has been added to the thyroidectomy-inoculation period. Altogether 21 litters (or groups) consisting of 184 rats were used. There were 117 takes in the thyroidectomized rats with 39 complete regressions. There were 40 controls with 36 takes and no regressions. Special emphasis has been placed on the regression of well-established tumors because this phenomenon appears to represent a condition of maximum resistance to tumor growth. There is, however, evidence of retarded tumor growth in those thyroparathyroidectomized rats that showed no regression but merely a slowed rate of growth. Thus on the 21st post-inoculation day the average tumor diameter was 27.8 mm. in 13 non-regression thyroidectomized rats against 33 mm. in 9 littermate controls. Measurements on 7, 14, 28 and 35th post-inoculation days likewise showed larger tumors in the controls. To establish that a regression had taken place it was required that the inoculated tumor progressively reach a size of 10-15 mm. before starting to shrink. Biopsy snippings examined microscopically from 30 such tumors in the thyroidectomized rats have shown sarcoma without exception. The regressions were almost always complete by the end of the third post-inoculation week and were usually accomplished without ulceration, but in a few there was adherence to the skin and ulceration. In the biopsy specimens of regressing tumors the necrosis was often widespread and much greater than that seen in tumors of like size in control animals. The controls have been followed until the animals died or until the tumors became huge ulcerated growths.