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543Determination of intestinal absorption in tumour bearing rats
S139 542
543 POSTOPERATIVE RADIATION THERAPY OF THE RHABDOMYOSARCOMA RIH OF THE RAT
Ulrich M. CarlI, Peter Sminia2, Jens Bahasen=, Gtlnther Fr0schlet, Hans-Peter Beck-Bomholdtt [~University DUsseldorf (FRG), ZUniversity of Amsterdam (NL), JUniversity Hamburg (FRG)]
Purpose: Postoperative radiotherapy is routinely applied in the treatment of several human tumours. To date systematic experimental investigations are only rarely available in this field. Material and Methods: Experiments were performed using the Rhabdomyosarcoma RI H of the WAG/Rij rat (with no signs of specific immunogenicity). Animals were randomized to different treatment schedules, consisting of operation or radiation treatment alone, the combination of both, either straight postoperatively or when recurrent tumour have reached operation-size. Tumours were excised at different sizes (0.1-4.5g) aiming for complete macroscopic resection. The radiation therapy comprised 60 Gy in 30 daily fractions over 6 weeks. Tumour growth delay and local tumour control were used as endpoints. Results: Preoperative tumour size determined the rate of recurrences. 50% of the tumours with a mass of 0.Sg were locally controlled by sole operation. With postoperative radiation therapy a local control rate of 50% was achieved for tumours with a mass of l.lg. For large turnouts (> I. I g), however, the rate and time course of relaps was similar for the groups using either radiation therapy alone or postoperative radiation therapy. Irradiation of recurrent tumours showed a similar growth kinetic as primarily irrradiated tumours. Conclusion: The tumour mass at excision governs the prognosis. Relatively small RIH tumours may recur despite of complete macroscopical resection. When applying postoperative radiation therapy (60 Gy/6 weeks) turnouts may be larger compared to sole operation. The factor is 1.4. Within a certain range of tumour sizes combined treatment with operation and radiation therapy can improve the outcome in cancer therapy considerably, whereas radiation therapy of recurrent, initially not sufficiently treated tumours is palliative natur, only.
Supported by the Spierling-Stifiung, Hamburg. FRG
544 FETAL RESORPTION IN PREGNANT TUMOUR BEARING RATS.
Gomes-Marcondes, M.C.C.; Cury, L.; Curt, R.. Depto Fisiologia e Bioflsica, Instituto de Biologia, UNICAMP, S~to Paulo, Brazil
D E T E R M I N A T I O N O F INTESTINAL ABSORPTION IN TUMOUR BEARING RATS Gomes-Marcondes M.C.C.; Honma H.N., Zanini E., Areas M.A. Depto Fisiologia e Biofisica, lnstituto de Biologia, UNICAMP, S,~u Paulo, Brazil Research on cancer using as a model tumor bearing rats have showed that most of the serum amino acids are used by neoplastic tissue in synthesis and oxidation processes. In the present study we evaluated the effects of Walker 256 carcinoma evolution in intestinal absorption of glucose, methionine and leucine of young and adult rats. Young (25 days) and adult (90 days) Wistar rats received 2.5 x 106 neoplastic ceils or saline solution via sc, and were housed in metabolic cases receiving standard diet. The animals were separated into four groups: young control (YC), adult control (AC) young tumor bearing (YW), adult tumor bearing (AW). At the 13th and 19th day after sc injection, young and adult rats, respectively, were submitted to a 12h starvation and prepared for surgery. The small intestine was isolated in vivo and perfused with 138.7 p.mol glucose, 167.5 p.mol DL methionine and 190.5 p.mol L leucine at a flux rate of 0.5 to 1.0 ml/min. Food intake was decreased in YW and AW groups and both groups presented a significant decrease in carcass weight. The tumor/carcass weight ratio was greater in YW than AW. The nitrogen balance was negative with a decrease of 61.9% in YW and 73.3% in AW animals in relation to the control group. Glucose absorption was significantly decreased in AW. There was a significant increase in intestinal absorption in methionine in both groups; leucine absorption was higher in young tumour-bearing rats. In addition, the results showed an exponential evolution of the tumour associated with a decrease in lean body mass (loss in carcass weight and negative nitrogen balance) especially in young rats. The decrease in glucose absorption observed in AW rats seemed not to impair the cancer evolution. The amino acid mobilization of host tissues associated with increase in methionine and leucine absorption, especially in young rats, suggest that these substracts are being used in oxidation and degradation process in those animals, providing energy and other substracts to neoplastic cell development. Research Support : FAEP-UNICAMP, CNPq Technical Assistance : A.S. Geraldo
545 RADIATION-INDUCED EMESIS: ANALYSIS OF 41' CONSECUTIVE S E M I N O M A PATIENTS UNDERGOING SUB-DIAPHRAGMATIC R A D I O T H E R A P Y (RT)
Maranzano E., Barone V., Piro F., Marafioti L., Latini P. U.O. Redioterapia Oncologica, Policlinico e Cattedra di Radioterapia, Universitfi - Perugia - Italy.
Women with pregnancy associated cancer comprise a small but clinically important group of patients. Studies on the influence of pregnancy on cancer prognosis have yielded conflicting results. Pregnancy has been reported to improve, as well as worsen, or not affect cancer prognosis. Metabolic adaptations to pregnancy are directed to ensure satisfatory growth and development of the fetus and to store energy for the fetus and mother for using in the immediate neonatal and lactation period. We studied the effects of the injection of Walker 256 neoplastic cells and ascites fluid in adult pregnant VVistar rats and its consequences on fetal development Alter mating, females were separated into groups: control (C), non pregnant tumour-bearing rats (VV), pregnant (P), pregnant turnout-bearing rats (PW), pregnant rats treated with 2,0 ml salina via ip (PS), pregnant females" injected with 2,0ml ascites fluid via ip (PA), pregnant injected with 2,0 ml inactivated ascites fluid via ip (PI). All groups were followed during 23 days. Only pregnant tumour-bearing rats (50% - PW) died between 17th and 19th day post-neoplastic implant. Carcass weight was significantly increased in all pregnant groups (P, PW, PS, PA, PI) as compared to C group while the carcass weight was deoreased in the W group. Tumour weight was smaller in PW than in W group. In addition, we observed that in PW and PA groups there was reduction in fetal and placent weight and placental necrosis, frequently accompaned by fetal death. Fetal resorption was higher in PW (25%) and PA(25,3%) groups than in P(2,9%), PS(8,1) and P1(6,3%) rats. These results indicate that both tumour development and ascites fluid injected during pregnancy promote similar damage effects on placent and fetus. These alterations were probably induced by increased synthesis and release of cytokines produced by the host and cancer cells. Technical Assistence: A.S. Geraldo Research support: FAEP-UNICAMP, CNPq
A number of studies assume that radiation-induced emesis can occur in approximatively 50% of patients after conventional fraetionation RT to the upper abdomen. Forty-one consecutive seminoma patients undergoing sub-diaphragmatic RT were analysed to record the incidence of nausea and vomiting and the therapeutic efficacy o f 5Hydroxitriptamine 3 (5-HT3) antagonists. Median age of patients was 34 years (range, 22-68 yrs) and follow-up ranged from 2-63 months. All patients received pars-aortic and ipsilateral pelvic lymph node RT using 18 MV linear accelerator photon beams. Dose and fraetionation were as follows: 1.5-1.8 Gy/day, 5 sessions per week, to a total dose of 25-30 Gy in stage ! (34 eases) or 35-45 Gy in stage II (7 cases) disease. Fourteen (34%) patients had no RT-induced sickness. Nausea without vomiting occurred in II (27%) patients. These were not treated with antiemetics because sickness was generally mild and tolerable. The remaining 16 (39%) eases presented nausea and vomiting requiring antiemetic drugs. Vomiting occurred within 2-10 clays from the start of RT and the frequency varied from 2 to 12 episodes (median, 4) on the first day of emesis. Patients experiencing vomiting were treated with oral 5-HT3 antagonists as follows: Ondansetron, 8 nag three times a day (10 eases) or Granisetron, 1 m8 two times a day (6 eases) from the first day of appearence of emesis until the last session of RT. No patients suffered vomiting aider 5-HT~ antagonist administration, whereas generally they still had mild nausea but not serious enough to discontinue RT. No relation was found between age of patients and incidence ofemesis. No side effects were encountered with either 5-HT3 antagonist dru 8. Oral administration of Ondansetron or Granisetron to seminoma patients experiencing sickness during sub-diaphragmatic RT, proved to be good symptomatic treatment which caused no side effects.
543 POSTOPERATIVE RADIATION THERAPY OF THE RHABDOMYOSARCOMA RIH OF THE RAT
Ulrich M. CarlI, Peter Sminia2, Jens Bahasen=, Gtlnther Fr0schlet, Hans-Peter Beck-Bomholdtt [~University DUsseldorf (FRG), ZUniversity of Amsterdam (NL), JUniversity Hamburg (FRG)]
Purpose: Postoperative radiotherapy is routinely applied in the treatment of several human tumours. To date systematic experimental investigations are only rarely available in this field. Material and Methods: Experiments were performed using the Rhabdomyosarcoma RI H of the WAG/Rij rat (with no signs of specific immunogenicity). Animals were randomized to different treatment schedules, consisting of operation or radiation treatment alone, the combination of both, either straight postoperatively or when recurrent tumour have reached operation-size. Tumours were excised at different sizes (0.1-4.5g) aiming for complete macroscopic resection. The radiation therapy comprised 60 Gy in 30 daily fractions over 6 weeks. Tumour growth delay and local tumour control were used as endpoints. Results: Preoperative tumour size determined the rate of recurrences. 50% of the tumours with a mass of 0.Sg were locally controlled by sole operation. With postoperative radiation therapy a local control rate of 50% was achieved for tumours with a mass of l.lg. For large turnouts (> I. I g), however, the rate and time course of relaps was similar for the groups using either radiation therapy alone or postoperative radiation therapy. Irradiation of recurrent tumours showed a similar growth kinetic as primarily irrradiated tumours. Conclusion: The tumour mass at excision governs the prognosis. Relatively small RIH tumours may recur despite of complete macroscopical resection. When applying postoperative radiation therapy (60 Gy/6 weeks) turnouts may be larger compared to sole operation. The factor is 1.4. Within a certain range of tumour sizes combined treatment with operation and radiation therapy can improve the outcome in cancer therapy considerably, whereas radiation therapy of recurrent, initially not sufficiently treated tumours is palliative natur, only.
Supported by the Spierling-Stifiung, Hamburg. FRG
544 FETAL RESORPTION IN PREGNANT TUMOUR BEARING RATS.
Gomes-Marcondes, M.C.C.; Cury, L.; Curt, R.. Depto Fisiologia e Bioflsica, Instituto de Biologia, UNICAMP, S~to Paulo, Brazil
D E T E R M I N A T I O N O F INTESTINAL ABSORPTION IN TUMOUR BEARING RATS Gomes-Marcondes M.C.C.; Honma H.N., Zanini E., Areas M.A. Depto Fisiologia e Biofisica, lnstituto de Biologia, UNICAMP, S,~u Paulo, Brazil Research on cancer using as a model tumor bearing rats have showed that most of the serum amino acids are used by neoplastic tissue in synthesis and oxidation processes. In the present study we evaluated the effects of Walker 256 carcinoma evolution in intestinal absorption of glucose, methionine and leucine of young and adult rats. Young (25 days) and adult (90 days) Wistar rats received 2.5 x 106 neoplastic ceils or saline solution via sc, and were housed in metabolic cases receiving standard diet. The animals were separated into four groups: young control (YC), adult control (AC) young tumor bearing (YW), adult tumor bearing (AW). At the 13th and 19th day after sc injection, young and adult rats, respectively, were submitted to a 12h starvation and prepared for surgery. The small intestine was isolated in vivo and perfused with 138.7 p.mol glucose, 167.5 p.mol DL methionine and 190.5 p.mol L leucine at a flux rate of 0.5 to 1.0 ml/min. Food intake was decreased in YW and AW groups and both groups presented a significant decrease in carcass weight. The tumor/carcass weight ratio was greater in YW than AW. The nitrogen balance was negative with a decrease of 61.9% in YW and 73.3% in AW animals in relation to the control group. Glucose absorption was significantly decreased in AW. There was a significant increase in intestinal absorption in methionine in both groups; leucine absorption was higher in young tumour-bearing rats. In addition, the results showed an exponential evolution of the tumour associated with a decrease in lean body mass (loss in carcass weight and negative nitrogen balance) especially in young rats. The decrease in glucose absorption observed in AW rats seemed not to impair the cancer evolution. The amino acid mobilization of host tissues associated with increase in methionine and leucine absorption, especially in young rats, suggest that these substracts are being used in oxidation and degradation process in those animals, providing energy and other substracts to neoplastic cell development. Research Support : FAEP-UNICAMP, CNPq Technical Assistance : A.S. Geraldo
545 RADIATION-INDUCED EMESIS: ANALYSIS OF 41' CONSECUTIVE S E M I N O M A PATIENTS UNDERGOING SUB-DIAPHRAGMATIC R A D I O T H E R A P Y (RT)
Maranzano E., Barone V., Piro F., Marafioti L., Latini P. U.O. Redioterapia Oncologica, Policlinico e Cattedra di Radioterapia, Universitfi - Perugia - Italy.
Women with pregnancy associated cancer comprise a small but clinically important group of patients. Studies on the influence of pregnancy on cancer prognosis have yielded conflicting results. Pregnancy has been reported to improve, as well as worsen, or not affect cancer prognosis. Metabolic adaptations to pregnancy are directed to ensure satisfatory growth and development of the fetus and to store energy for the fetus and mother for using in the immediate neonatal and lactation period. We studied the effects of the injection of Walker 256 neoplastic cells and ascites fluid in adult pregnant VVistar rats and its consequences on fetal development Alter mating, females were separated into groups: control (C), non pregnant tumour-bearing rats (VV), pregnant (P), pregnant turnout-bearing rats (PW), pregnant rats treated with 2,0 ml salina via ip (PS), pregnant females" injected with 2,0ml ascites fluid via ip (PA), pregnant injected with 2,0 ml inactivated ascites fluid via ip (PI). All groups were followed during 23 days. Only pregnant tumour-bearing rats (50% - PW) died between 17th and 19th day post-neoplastic implant. Carcass weight was significantly increased in all pregnant groups (P, PW, PS, PA, PI) as compared to C group while the carcass weight was deoreased in the W group. Tumour weight was smaller in PW than in W group. In addition, we observed that in PW and PA groups there was reduction in fetal and placent weight and placental necrosis, frequently accompaned by fetal death. Fetal resorption was higher in PW (25%) and PA(25,3%) groups than in P(2,9%), PS(8,1) and P1(6,3%) rats. These results indicate that both tumour development and ascites fluid injected during pregnancy promote similar damage effects on placent and fetus. These alterations were probably induced by increased synthesis and release of cytokines produced by the host and cancer cells. Technical Assistence: A.S. Geraldo Research support: FAEP-UNICAMP, CNPq
A number of studies assume that radiation-induced emesis can occur in approximatively 50% of patients after conventional fraetionation RT to the upper abdomen. Forty-one consecutive seminoma patients undergoing sub-diaphragmatic RT were analysed to record the incidence of nausea and vomiting and the therapeutic efficacy o f 5Hydroxitriptamine 3 (5-HT3) antagonists. Median age of patients was 34 years (range, 22-68 yrs) and follow-up ranged from 2-63 months. All patients received pars-aortic and ipsilateral pelvic lymph node RT using 18 MV linear accelerator photon beams. Dose and fraetionation were as follows: 1.5-1.8 Gy/day, 5 sessions per week, to a total dose of 25-30 Gy in stage ! (34 eases) or 35-45 Gy in stage II (7 cases) disease. Fourteen (34%) patients had no RT-induced sickness. Nausea without vomiting occurred in II (27%) patients. These were not treated with antiemetics because sickness was generally mild and tolerable. The remaining 16 (39%) eases presented nausea and vomiting requiring antiemetic drugs. Vomiting occurred within 2-10 clays from the start of RT and the frequency varied from 2 to 12 episodes (median, 4) on the first day of emesis. Patients experiencing vomiting were treated with oral 5-HT3 antagonists as follows: Ondansetron, 8 nag three times a day (10 eases) or Granisetron, 1 m8 two times a day (6 eases) from the first day of appearence of emesis until the last session of RT. No patients suffered vomiting aider 5-HT~ antagonist administration, whereas generally they still had mild nausea but not serious enough to discontinue RT. No relation was found between age of patients and incidence ofemesis. No side effects were encountered with either 5-HT3 antagonist dru 8. Oral administration of Ondansetron or Granisetron to seminoma patients experiencing sickness during sub-diaphragmatic RT, proved to be good symptomatic treatment which caused no side effects.