Of 340 patients with histologically proven colorectal carcinoma, hepatic metastases were diagnosed in 90 (26 per cent), in 50 at the time of initial surgery (synchronously) and in 40 during the post-operative follow-up (metachronously). At the time of initial surgery, plasma carcinoembryonic antigen (CEA) levels were markedly elevated in patients with synchronous metastases and normal or only moderately elevated in those with metachronous metastases. During follow-up, CEA levels in the entire group of patients with metastases remained normal in 8 per cent and rose in the remainder: very quickly in 85 per cent and slowly in 15 per cent. Hepatic metastases were diagnosed by strict scintigraphic criteria in 70 per cent of patients and were suggested by liberal criteria in the remainder. During follow-up, hepatic metastases progressed in the scintigraphic image from those defined by liberal to those diagnosed by strict criteria. In two-thirds of the patients, liver scintigraphy proved to be superior to the CEA test in diagnosing hepatic metastases by strict criteria; in the majority of the remainder of patients, the CEA test, particularly in cases with a pattern of fast increase of CEA in plasma, suggested metastases before a definite diagnosis could be made by liver scintigraphy. In only 3 per cent of the patients neither liver scintigraphy nor the CEA test were indicative of metastases. Thus, the two diagnostic modalities, when combined, could attain a sensitivity of 97 per cent, when patients with persistently rising CEA levels and concomitant liver lesions defined by the liberal criteria were grouped with those for whom scintigraphy was unequivocal.
This study is aimed at elucidating the mechanism of paradoxical rise in plasma ACTH levels in response to glucocorticoids, observed by several authors in bilaterally adrenalectomized patients with Cushing's disease. Six control subjects and fourteen patients bilaterally adrenalectomized for Cushing's disease were given a dose of 200 mg hydrocortisone sodium succinate by 3-5 mm i.v. injection. Plasma ACTH (in 6 patients), serum cortisol, growth hormone (GH) and insulin and blood glucose levels were estimated at 0, 30, 60, 90, and 120 minutes. The administration of hydrocortisone significantly suppressed plasma ACTH levels only at 60 min. In one case a slight rise in ACTH level during the test was observed. A significant fall in blood glucose levels was found only in the adrenalectomized patients. No significant changes in serum insulin and GH levels were noted. The possible mechanisms are discussed, especially the potential role of transient glucose deficiency in the pathophysiology of plasma ACTH increase in response to hydrocortisone in the bilaterally adrenalectomized patients.
Re-irradiation (Re-RT) for rectal cancer (RC) in patients with prior pelvic radiation therapy (RT) has been shown to be effective. However, safety remains a principle concern, particularly with respect late toxicities. Toxicity mitigation is accomplished in a variety of ways, including hyperfractionation and the use of more conformal treatment modalities such as intensity-modulated radiation therapy (IMRT) and proton therapy (PT). Published data on the use of PT for RC is largely limited to dosimetric studies, with little to no published clinical outcomes, especially with Re-RT. We hypothesize that PT may further reduce toxicity seen in these patients. Materials/Methods: A single institutional retrospective IRB-approved analysis of all RC patients with any prior pelvic RT re-irradiated with any modality from 2006-present was performed. We collected patient and treatment characteristics, including prior diagnosis, re-irradiation records, and acute and late toxicities. Outcomes, including overall Survival (OS) and Local Control (LC), and incidence of Grade 3+ late toxicities (Gr3+T) were estimated using Kaplan-Meier (KM). Results: Forty-six patients (median follow-up 16 months) received Re-RT from 2007-2018, 23 with photons (median follow-up 15 months) and 23 with protons (median follow-up 16 months). Thirty-four patients had recurrent RC [median prior dose 50.4 Gy (43.2-67.2)] and 12 patients de novo RC and variable prior RT (10 for prostate, 1 for seminoma, 1 for ovarian). Median Re-RT dose was 45.3 Gy [(9.6.0-60.0); 34/46 treated BID], median time to Re-RT 35 months (7.2-712), and 40 received concurrent chemotherapy. Twelve underwent surgical resection (10 R0 incl. 2 pCR; 1 R1; 1 R2). Three patients experienced grade 3 acute toxicities, and no acute Grade 4-5 toxicities were observed. Six patients treated with photons had grade 3+ late toxicities, including one grade 5 toxicity, and 2 patients treated with protons had grade 3+ late toxicities, including one grade 5 occurring in a patient with history of significant injury from prior RT. Rates of 1-yr Gr3+ toxicity were 13.8% (95% CI 7.9-19.7%) for the whole cohort, and 23.3% (95%CI 12.7-33.9%) and 4.8% (95%CI 0.2-9.4%) for photons and protons, respectively (pZ0.137). One-year LC and 1-year OS for the whole cohort were 78%+/-7.6% and 75%+/-6.5%, respectively Conclusion: Acceptable rates of acute and late toxicity are demonstrated in this series inclusive of patients treated with photons/PT. This is notably the largest reporting of PT results. Though no statistically significant difference in 1-year Gr3+ toxicity between photon and PT was observed, results are early but promising. We await maturation of results with longer followup and larger cohort.
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