Reliability of Transesophageal Pacing in the Assessment of Sinus Node Function in Patients with Sick Sinus Syndrome

The purpose of this study was to find out whether transesophageal pacing could be utilized for assessment of sinus node function in patients with sick sinus syndrome (SSS). In 17 patients with SSS (study group) we compared the results of sinus node tests obtained both in the basal state and after pharmacological autonomic blockade by endocavitary stimulation and, 24 hours later, by transesophageal pacing. In another group of 17 patients with SSS (control group), we compared the results obtained by two endocavitary studies. In "study group", sinus cycle length (SCL) and corrected sinus node recovery time (CSRT) did not show significant differences between the two studies both in the basal state and after autonomic blockade, whereas sinoatrial conduction time (SACT) was more prolonged during esophageal pacing (P less than 0.01). In "control group", sinus node measures did not show significant differences between the two studies. In the "study group," the following coefficients of correlation were obtained in the basal state; SCL, r = 0.65, CSRT, r = 0.57, SACT, r = 0.52 and after autonomic blockade: SCL, r = 0.95, CSRT, r = 0.62 and SACT, r = 0.53. In the basal state, the correlation for SCL and CSRT between the two studies was lower in the "study group" than in the "control group" (P less than 0.05), whereas after autonomic blockade the correlation for sinus node measures did not show significant differences between the two groups of patients. These data suggest that transesophageal study influences the autonomic tone regulating the sinus node; however, it is not responsible for important variations in sinus node measures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prospective multicenter study on the clinical utility of ca-72.4 in postmenopausal patients with pelvic mass

The study objective was to evaluate the sensitivity and specificity as well as the positive predictive value and negative predictive value of CA 72.4 and CA 125 determination, separately and in combination, for diagnosing ovarian tumors in post-menopausal women with pelvic mass. The 299 patients recruited in this study underwent gynecological examination, plasma determination of CA 72.4 and CA 125, and laparotomy with histological definition of pelvic mass. CA 72.4 assay values were under 3.9 U/ml in 194 cases (70.8%); values ranged from 3.9 to 4.5 U/ml in 7 cases (2.5%) and were greater than 4.5 U/ml in 73 cases (26.6%). CA 72.4 assay was positive (>4.5 U/ml) in 56 cases (57.1%) of malignant ovarian pathology, in 4 cases (25%) of malignant extra-ovarian pathology as well as in 9 cases (7.1%) of benign ovarian pathology and in 4 cases (11.8%) of benign extra-ovarian pathology. With a cut-off at 3.9 U/ml, CA 72.4 showed a specificity of 91.3% and a sensitivity of 62.2%, whereas with a cut-off at 4.5 U/ml specificity was 92.9% and sensitivity 57.1%. Results of CA 125 assay for diagnosing a pelvic neoplasia (ovarian or extra-ovarian), showed a specificity of 85.3% and sensitivity of 68.8%. The agreement of the two markers (CA 125 and CA 72.4) as negative or positive shows a specificity of 77% and a sensitivity of 84.7% for ovarian cancer and a specificity of 73.5% and sensitivity of 75% for the diagnosis of pelvic neoplasias.     

Efficacy and tolerability of cancer neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin - a progress report of 200 patients with advanced solid neoplasms

The recent advances in psychoneuroimmunology have demonstrated the existence of a psychoneuroendocrine control of the antitumor immunity. Our previous preliminary studies indicated the possibility of amplifying the biological and therapeutic efficacy of IL-2 cancer immunotherapy by immunomodulating neurohormones, mainly the pineal indole melatonin (MLT), in most advanced solid tumors, including those which generally do not respond to IL-2 alone. This study reports on the results obtained by low-dose IL-2 plus MLT in 200 patients with advanced solid neoplasms, for whom no other effective standard therapy was available. Non-small cell lung cancer, pancreatic adenocarcinoma, hepatocarcinoma, colon cancer and gastric cancer were the neoplasms most frequently detected in our patients. In addition, all patients had a life expectancy less than 6 months. IL-2 was given subcutaneously at 3 million IU/day for 6 days/week for 4 weeks; MLT was given orally at 40 mg/day. In non-progressing patients, a second cycle was given after a 21-day rest period; then, patients underwent a maintenance period consisting of one week of therapy every month until progression. A complete response (CR) was achieved in 4 patients (hepatocarcinoma 2; pancreas 1; gastric cancer 1), a partial reasponse (PR) was achieved in 36 patients (lung 12; liver 6; stomach 4; pancreas 3; colon 3; breast 2; miscellaneous 6). Tumor response rate (CR+PR) was 40/200 (20%) patients. Longer than one year survival was achieved in 79 (39%) patients. Toxicity was mild in all patients, and therapy was administered as a home therapy. The present study confirms in a great number of patients the possibility to induce objective tumor regressions in most advanced solid tumor histotypes by low-dose IL-2 plus MLT. Thus, immunotherapy with IL-2 and MLT may be considered as a new well tolerated and effective therapy of almost all advanced solid tumors, including those which do not respond to IL-2 alone or to chemotherapy.     

Immunotherapy with subcutaneous low dose interleukin-2 plus melatonin as salvage therapy of heavily chemotherapy-pretreated ovarian cancer

Preliminary results showed that IL-2 immunotherapy may be effective in the treatment of recurring advanced ovarian cancer. The pineal neurohormone melatonin (MLT) has been proven to amplify IL-2 efficacy by counteracting macrophage-mediated immunosuppression. On this basis, a pilot phase II study of low-dose IL-2 plus MLT was performed in advanced ovarian cancer patients progressing after at least 3 previous polychemotherapeutic lines. The study included 12 evaluable patients. IL-2 was injected subcutaneously at 3 million IU/day for 6 days/week for 4 weeks, by repealing the cycle after a al-day rest period in nonprogressing patients. MLT was given orally at 40 mg/day. No complete response was seen. A partial response was achieved in 2/12 (16%) patients. A stable disease was obtained in 5 other patients, whereas the remaining 5 patients progressed. The treatment was well tolerated. This preliminary study suggests that immunotherapy with low-dose IL-2 plus MLT may represent a well tolerated and promising therapy of advanced ovarian cancer progressing on standard medical treatments.     

Brachytherapy for isolated vaginal recurrences from endometrial carcinoma

AIMS AND BACKGROUND: Isolated vaginal recurrences of endometrial carcinoma are rare, and prognostic factors that predict treatment outcome are still not well defined. The aim of the present study was to evaluate the results of brachytherapy in isolated vaginal recurrences from endometrial carcinoma. METHODS: Thirty-five patients with isolated vaginal recurrences were treated with brachytherapy with intravaginal ovoids or cylinders that were calculated to deliver 6000 to 7000 cGy at the surface. Patients were assessed for size and location of recurrence at presentation, response and complications from therapy. RESULTS: Treatment was well tolerated by most patients. Grade 2 toxicity occurred in 4 patients (3 cases of partial vaginal stenosis and one proctitis). Complete response to radiation was observed in all patients, and an overall 9 failures were observed (4 local, 4 distant and 1 local plus distant). Twenty patients (57%) were alive without evidence of disease at 3 to 11 years following treatment. Site of vaginal recurrence (upper third versus others) and long (more than 12 months versus less than 12 months) interval from hysterectomy were the only factors significantly related to local failures. CONCLUSIONS: Isolated vaginal recurrences following hysterectomy for endometrial carcinoma can be treated with brachytherapy with a low rate of severe toxicity.     

Paradoxical stimulation of prolactin secretion by L-dopa in metastatic prostate cancer and its possible role in prostate-cancer-related hyperprolactinemia

OBJECTIVE: In addition to sex steroids, prolactin (PRL) may also stimulate prostate cancer growth. Abnormally high blood levels of PRL have been noted in metastatic prostate cancer patients. However, most studies have been limited to the evaluation of basal levels of PRL rather than to investigate its secretion in response to classical endocrine dynamic tests. This study was carried out to analyze PRL secretion in metastatic prostate cancer patients both at basal conditions and in response to L-Dopa and metoclopramide, which represents the most classical inhibitory and stimulatory tests for PRL secretion, respectively. METHODS: The study included 12 patients with metastatic prostate cancer. On separate occasions, PRL secretion was evaluated in response to L-Dopa (500 mg orally) and to metoclopramide (10 mg i.v. as a bolus). Serum levels of PRL were measured by RIA. RESULTS: Mean PRL concentrations significantly increased after metoclopramide administration, even though no PRL response occurred in 6 of 12 patients. L-Dopa was unable to reduce PRL levels, which, in contrast, paradoxically significantly increased in response to L-Dopa, with mean values comparable to those achieved after metoclopramide injection. CONCLUSION: By showing a paradoxical stimulatory effect of L-Dopa on PRL secretion and a lack of response to metoclopramide in some patients, this study would suggest the existence of evident alterations in the neuroendocrine regulation of PRL release in advanced prostate cancer.     

Surgery-induced decline in circulating dendritic cells in operable cancer patients: a possible explanation of postoperative immunosuppression

BACKGROUND/AIMS: The recent advances in the immunobiology of tumor have demonstrated the essential role of dendritic cells in anticancer immunity. Dendritic cells activate anticancer immunity by secreting interleukin-12 and by activating T helper lymphocytes, with the following production of interleukin-2. Since surgery-induced immunosuppression has been proven to be associated with a decline in the blood levels of both interleukin-2 and interleukin-12, it could depend at least in part on a transient deficiency of dendritic cells system. Unfortunately, at present there are no data about changes in circulating dendritic cell number during the postoperative period. This preliminary study was performed to evaluate the influence of surgery on dendritic cell number in the peripheral blood. METHODOLOGY: The study included 14 consecutive operable gastrointestinal tract cancer patients, who were evaluated before and at day 7 of the postoperative period. The control group consisted of 50 healthy subjects. Immature (CD 123+) and mature (CD 11+) dendritic cell subsets were measured by FACS and monoclonal antibodies. RESULTS: Cancer patients showed a significantly lower mean number of immature dendritic cells with respect to that found in controls. The mean number of mature dendritic cells was also lower in patients than in controls, without, however, significant differences. Finally, surgery induced a statistically significant decline in the mean number of both immature and mature dendritic cells, and the decrease was particularly pronounced for immature dendritic cells. CONCLUSIONS: In addition to the well-demonstrated surgery-induced lymphocytopenia, this preliminary study shows that the surgical treatment may determine a significant decrease in circulating immature and mature dendritic cells. Because of the fundamental role of dendritic cells in regulating the immune responses, surgery-induced decline in circulating dendritic cells number could play a role in determining the immunosuppressive status, which characterizes the postoperative period.     

Thrombopoietic properties of 5-methoxytryptamine plus melatonin versus melatonin alone in the treatment of cancer-related thrombocytopenia

Recent studies have shown that the hematopoietic system is under neuroendocrine control. In particular, thrombopoiesis has been proven to be stimulated by melatonin, and the pineal indole has been shown to be effective in the treatment of thrombocytopenia resulting from different causes. At present, however, there are no data concerning the possible thrombopoietic activity of pineal indoles other than melatonin. The present study was carried out to evaluate the effect of a concomitant administration of the pineal indole 5-methoxytryptamine in patients with cancer-related thrombocytopenia who did not respond to melatonin alone. The present study included 30 patients, who were randomized to receive melatonin alone (20 mg/day orally in the evening) or melatonin plus 5-methoxytryptamine (1 mg/day orally in the early afternoon). A normalization of platelet count was achieved in 5/14 (36%) patients treated with melatonin plus 5-methoxytryptamine and in none of the patients treated with melatonin alone (P < 0.05). Moreover, mean platelet number significantly increased only in the patients treated with melatonin plus 5-methoxytryptamine. This preliminary clinical study would suggest that 5-methoxytryptamine, a pineal indole, may also exert thrombopoietic activity. Further studies, however, will be required to establish whether 5-methoxytryptamine may play a direct thrombopoietic activity, or whether it may act by improving melatonin's efficacy.