Biomedical subjects
Publications and source records attributed to G Gardani.
About 600 cases of extrinsic masses in the large intestine have been examined by double contrast clysma; radiological signs of modifications in the intestinal walls are discussed with special reference to the distinction between compression, adherence, infiltration, etc. Some cases are reported.
319 cases of breast pathology of doubtful clinical diagnosis were studied by means of thermography and mammography, with histological verification: 214 proved to be malignant tumours and 105 benign. The role of thermography is discussed on the basis of these results; it would appear to be restricted to diagnostic aid status associated with other procedures, particularly clinical examination and mammography.
BACKGROUND: The current treatment options for cancer of the base of the tongue and glosso-epiglottic region are surgery, radiotherapy, or a combination of both modalities. Comparisons between different modalities are not common in the literature, and a real standard of treatment has not yet been established. The purpose of our study was to evaluate the results of treatment in a large series of patients from 18 Italian institutions in relation to the main treatment adopted. METHODS: The present study is a retrospective survey. The series was divided into a combined surgery group and a radiotherapy group. The Kaplan-Meier method and the log-rank test were used for survival calculations and comparisons. RESULTS: Eight hundred patients were registered (25.7% stage III and 62% stage IV), 336 in the surgery and 372 in the radiotherapy group. Conventional fractionation was adopted in almost all cases. The five-year overall and disease free survival of the whole series was 32% and 38%, respectively. Survival was slightly better for patients with tumors of the glosso-epiglottic region than for those with a tumor of the base of the tongue. Five-year disease-free survival was 55% for patients treated with surgery +/- radiochemotherapy and 26% for those submitted to radiotherapy alone or in combination with chemotherapy. As far as the total dose and the treatment duration were concerned, only 26% of the patients of the radiotherapy group met the established criteria of adequacy, but in patients with adequate radiation the control rate was better only for small tumors (T1-T2). CONCLUSIONS: The results in patients treated with surgery +/- postoperative radiotherapy were similar to or better than those reported in the best series in the literature. By contrast, the survival rate of irradiated patients was lower than those reported by other centers.
The definitive cure rate for clinical stage 1 testicular seminoma is very close to 100%, and prophylactic irradiation of the regional lymph nodes is associated with a low morbidity. Nevertheless, in recent years a "wait-and-see" policy has been proposed by some researchers. We analysed the cost/benefit ratio of radiotherapy (RT) by review of the case histories of 299 patients treated at the Department of Radiotherapy of the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan from January 1968 to December 1989. The 5-year overall survival was 99% (97.5% at 10 years), while the 10-year disease-free survival was 96%. The recurrence rate was 2.3%, but no patient relapsed in the irradiated areas. Acute toxicity was very moderate with only 4 (1.3%) serious radiation sequelae occurring 6 to 27 years after treatment. However, 9 second malignancies (3%) were observed. Lastly, we have calculated the costs for our National Health Service comparing surveillance policy and prophylactic irradiation.
AIMS AND BACKGROUND: To evaluate the effectiveness of external radiation therapy (ERT), alone or combined with endoluminal brachytherapy (BRT), following percutaneous transhepatic biliary drainage (PTBD) in the treatment of patients affected by inoperable cholangiocarcinoma. METHODS & STUDY DESIGN: From September 1980 to June 1996, 130 jaundiced patients affected by inoperable cholangiocarcinoma were submitted to PTBD at the Division of Radiology C of the National Cancer Institute of Milan. Nineteen were excluded from the present analysis due to the short survival after PTBD (< 30 days). The other 111 patients were divided into three groups according to the following therapy: no further treatment after palliative PTBD in 89 patients (80%, group 1); ERT in 10 patients (9%, group 2); ERT plus BRT in 12 patients (11%, group 3). All the ERT + BRT patients were enrolled after 1990 and were treated with high-energy photon beams followed by endobiliary insertion of one or two iridium-192 wires. RESULTS: Median overall survival among the 111 assessable patients was 126 days; for groups 1, 2 and 3 it was 108, 345 and 428 days, respectively. The patients submitted to radiotherapy (ERT alone or ERT + BRT) were evaluated by radiologic examinations after the end of radiation. In group 2, a partial remission in 3 cases, a progression of disease in 1 case, and no change in 6 cases were observed. Among the patients of group 3, complete remission in 5 and partial remission in 7 patients were achieved. In all the patients achieving complete remission, the PTBD could be removed. CONCLUSIONS: The combination of ERT plus BRT improves survival and quality of life of the patients submitted to PTBD for cholangiocarcinoma. Under the technical point of view, radiation treatment is easy to perform, but much caution is required in defining clinical and planning target volumes. Moreover, drainage during the radiation treatment has to be submitted to a very meticulous surveillance.
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Recent advances in immunobiological knowledge have suggested the possibility of enhancing the therapeutic activity of various chemotherapeutic agents by a concomitant administration of anti-oxidant drugs and/or immunomodulating neurohormones. In particular, the pineal neurohormone melatonin (MLT), which is able to exert both antioxidant and immunomodulating effects, has been proven to enhance the efficacy of various chemotherapeutic drugs, namely cisplatin, anthracyclines and 5-fluorouracil, whereas at present there are no data about its possible influence on cytotoxic drugs effective in the treatment of colon cancer other than 5-fluorouracil, such as irinotecan (CPT-11). The present study was performed to evaluate the influence of a concomitant administration of MLT on CPT-11 therapeutic activity in metastatic colorectal cancer. The study included 30 metastatic colorectal cancer patients progressing after at least one previous chemotherapeutic line containing 5-fluorouracil, who were randomized to be treated with CPT-11 alone or CPT-11 plus MLT. According to a weekly low-dose schedule, CPT-11 was given i.v. at 125 mg/m2/week for 9 consecutive weeks. MLT was administered orally at 20 mg/day during the dark period of the day. No complete response was observed. A partial response (PR) was achieved in 2 out of 16 patients treated with CPT-11 alone and in 5 out of 14 patients concomitantly treated with MLT. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with CPT-11 alone and in 7 out of 14 patients treated with CPT-11 plus MLT. Therefore, the percent of disease-control achieved in patients concomitantly treated with MLT was significantly higher than that observed in those treated with chemotherapy alone (12 out of 14 vs 7 out of 16, p < 0.05). The only important toxicity was diarrhoea grade 3-4, which occurred in 6 out of 16 patients treated with CPT-11 alone and in 4 out of 14 patients treated with CPT-11 plus MLT, which required a 50% dose reduction. However, taken together, patients treated with CPT-11 at 50% of the planned dose showed a percent of disease control comparable to that achieved in patients who had no dose reduction (6 out of 10 vs 13 out of 20). This preliminary study shows that the efficacy of weekly low-dose CPT-11 in pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily administration of the pineal hormone MLT, according to the results previously reported for other chemotherapeutic agents. Moreover, since the dose reduction of CPT-11 does not influence its efficacy, the dose of CPT-11 for successive studies might be not greater than 70 mg/m2.
From January 1976 to December 1986, 199 patients with oropharyngeal cancer were submitted to definitive radiotherapy. Survival and local control were analyzed and related to different parameters--i.e, T and N categories, histopathologic grading, tumor location, patients age, and radiation dose. Fifty-six per cent of patients (111/199) died from neoplastic disease within 5 years. Local progression, recurrence or metastases were observed in 149 cases (75%). Ninety-three per cent of first failures (138/149) were related to residual disease or to locoregional relapse while distant metastases occurred in 14 patients only. The majority of locoregional failures (94%) appeared within 2 years, with a mean disease-free interval of 8 months. Tumor recurrence in the primary location was observed to be the first cause of failure in 78% of relapsed patients; moreover, it was the sole cause of failure in half of the unfavorable events. On the contrary, nodal relapse appeared in 38% of treatment failures and in 12% only it was the sole cause of failure. Overall and disease-free survival were observed to depend mainly on T and N categories, while histopathologic grading was seen to affect only early response rate. No significant differences were observed depending on tumor site and patients age. Local control rates depended on total radiation dose, but the difference between low dose (NSD less than 1700) and high dose (NSD greater than 1700) was significant only for T1 and T2 patients.
In view of its potential action as a growth factor, the evidence of abnormally high blood levels of prolactin (PRL) is associated with a poor prognosis in metastatic breast cancer. Moreover, metastatic breast cancer-related hyperprolactinemia has proven to counteract the efficacy of cancer chemotherapy. The negative influence of high blood levels of PRL on the efficacy of chemotherapy in metastatic breast cancer has been confirmed by previous preliminary studies, showing that the concomitant administration of the anti-prolactinemic dopaminergic agent bromocriptine may enhance the therapeutic effect of chemotherapy. However, the clinical use of bromocriptine is limited by its short duration and gastrointestinal toxicity. Therefore, new anti-prolactinemic drugs, characterized by less toxicity and a longer duration of activity, such as Cabergoline (CBG), could be more appropriated to control PRL secretion in breast cancer. On this basis, a study was planned to evaluate the efficacy and tolerability of a concomitant administration of CBG with weekly low-dose Taxotere (TXT) in pretreated metastatic breast cancer under chemotherapy. The study group comprised 70 metastatic breast cancer patients (females), pretreated with at least one previous chemotherapeutic line containing anthracyclines, who were randomized to be treated with TXT alone or TXT plus CBG. TXT 25 mg/m2 was given i.v. at weekly intervals for at least 9 consecutive cycles. CBG was given orally at 0.5 mg once per week. Abnormally high pre-treatment levels of PRL were seen in 24/70 (34%) patients, 11 of whom were treated with TXT plus CBG, whereas the other 13 received TXT alone. CBG induced a complete normalization of the PRL levels in all patients within the first two weeks of therapy, whereas no normalization of PRL occurred spontaneously in patients treated with chemotherapy alone. The objective tumor regression rate was significantly higher in patients concomitantly treated with CBG than in those who received chemotherapy alone (31/34 vs 13/36, p < 0.05), and this difference was particularly evident in patients with high PRL levels prior to therapy (6/11 vs 2/13). No CBG-related toxicity occurred. On the contrary, chemotherapy-induced asthenia was significantly lower in patients concomitantly treated with CBG (5/34 vs 11/36, p < 0.05). This study shows that the chemoneuroendocrine therapy of weekly low-dose TXT plus the anti-prolactinemic drug CBG is a new, effective and well-tolerated therapy for metastatic breast cancer. It may also be recommended in heavily pretreated patients or in those with poor clinical status.
The evaluation of the biological status of cancer patients should not be limited only to investigation of immune reactivity, but should also include analysis of the endocrine condition, namely concerning those hormones which have appeared to be tumor growth factors, such as prolactin (PRL) for breast and prostate carcinomas. This statement is justified by the fact that the evidence of abnormally high serum concentrations of PRL has been proven to be associated with poor prognosis in breast and prostate cancer patients. Moreover, since hyperprolactinemia negatively influences the efficacy of anticancer therapies in breast cancer, it could be fundamental to achieve a normalization of PRL levels by long-acting dopaminergic agents, such as cabergoline. On this basis, a study was planned to evaluate the effect of cabergoline on PRL levels in hyperprolactinemic metastatic breast cancer subjects. The study included 20 hyperprolactinemic metastatic breast cancer subjects, who were randomized to receive no therapy or cabergoline at 0.5 mg/week orally for 4 consecutive weeks. Cabergoline therapy induced a normalization in all patients, whereas no spontaneous normalization of PRL levels occured in the control group. These results show that a weekly oral administration of the long-acting dopaminergic agent cabergoline is a well tolerated and effective treatment of metastatic breast cancer-related hyperprolactinemia. The possible prognostic impact of PRL normalization needs to be established by successive studies.
Lymphocytopenia is one of the most negative biological prognostic factors in cancer patients. Lymphocytopenia may depend on tumor progression, or on various anticancer therapies. In particular, radiotherapy (RT) may induce direct lymphocyte damage. The present study was carried out to evaluate the influence of pelvic irradiation on lymphocyte number and lymphocyte subpopulations in patients with gynecologic tumors. The study included 40 patients affected by locally limited or advanced uterine tumors, who underwent pelvic irradiation for a total dose of 50.4 Gy. RT induced a significant decline in total lymphocyte number, with values lower than 500/mm3 in 29/40 (73%) patients and with a mean decrease of 71 +/- 4%. In the same way, T lymphocyte, CD4, CD8 and NK cell mean numbers significantly decreased under RT. The decline in NK and CD8 cells was limited to the first 2-3 weeks of irradiation, whereas that involving T lymphocytes and CD4 cells was progressive and persistent until the end of RT. Finally, the decline in total lymphocyte number was significantly greater in patients who had no tumor regression in response to RT. This study confirms that pelvic RT may induce severe lymphocytopenia which could negatively influence the efficacy of RT itself.
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From January 1968 through December 1985, 123 patients with subdiaphragmatic lymph node metastases from testicular seminoma were observed. Eighty-five patients presented with metastases not bigger than 5 cm (stage II low), and they were all treated with radiotherapy (target dose: 35-45 Gy). Out of 38 patients with advanced retroperitoneal disease (because of metastases bigger than 5 cm: stage II, bulky), 18 were treated with radiotherapy, 14 with chemotherapy, and 6 with combined radiotherapy and chemotherapy; moreover, 14 out of 38 patients underwent surgical treatment (whole/partial lymph node resection). Actuarial relapse-free survival rate has proven higher for "low" patients than for "bulky" ones, both at 5 years (85.4% versus 75.8%) and at 10 years (83.5% versus 75.8%). On the contrary, overall survival has been higher for "low" patients at short-term follow-up only (90.4% vs 83.9% at 5 years), while long-term follow-up (10 years) has proven the same in both groups. Relapses (22 cases) occurred within 2 years in 75% of cases, and within 3 years in 90%. Overall incidence of lymph node recurrence has been 10.6%, higher in "bulky" patients (13.3% if treated with radiotherapy alone and 21.4% if treated with chemotherapy and/or surgery). Distant metastases occurred in 8.1% of cases. Long-term salvage treatment by chemotherapy was performed on 1/13 failures in stage II "low" patients and in 3/9 failures in stage II "bulky" patients. Four patients underwent effective salvage therapy in the "low" group, 3 by radiotherapy and 1 by surgery. The authors stress how curative radiotherapy appears to be the best treatment for retroperitoneal lymph node metastases less than 5 cm diameter, while chemotherapy is still to be demonstrated to yield better results than radiotherapy as first treatment for patients with advanced abdominal disease.
At Istituto Nazionale Tumori of Milan four patients with histologically proven angiosarcoma of the breast were evaluated by mammography and telethermography. This is a highly malignant rare tumor which occurs more frequently in young women. The authors outline that only 90 cases have been reported in the literature (once radiologically described in 1966) and analyze clinical and especially mammographic and thermographic signs. Radiological findings simulate those of filloiden tumors or giant fibroadenomas while thermographic patterns show a nearly generalized high hyperthermia. Therefore both methods should be associated for early diagnosis and improvement of the prognosis.
Percutaneous biliary drainage is an excellent method to relieve the acute symptoms related to neoplastic stenoses of extrahepatic bile ducts. However, survival rates are low and the quality of life of these patients is poor. High dose irradiation--combined with external beams (ERT) and intraluminal brachytherapy (BRT) through percutaneous drainage--allows effective disease control and, therefore, not only higher survival rates but also a much better quality of life when drainage can be removed after bile duct stenosis resolution. March, 1990, through March, 1993, eleven patients (8 with extrahepatic cholangiocarcinomas and 3 with extrinsic tumors) were treated with combined ERT (40-60 Gy, 6-15 MV X-rays) and intraluminal BRT (6-25 Gy, 192Ir wire, LDR). In 8 patients the biliary stenosis was resolved, completely (CR) in 5 and partially (PR) in 3, as shown by posttreatment cholangiography. In 5 patients biliary drainage could be removed for an average 9 months' period; 3 of 11 patients did not respond to treatment at all (NR). Average overall survival was 14 months: 11 months for NR patients and 16.5 months for CR+PR patients. Treatment complications were acceptable: in two patients only treatment had to be discontinued, both during BRT. Two cases of high grade postirradiation stenosis were observed, both resolved with percutaneous cholangioplasthy.
Over a 7-year period, in 408 patients aged 70 years or more, 413 early breast cancers were treated as follows: quadrantectomy, axillary dissection, and radiotherapy (QUART) in 142 patients, wide lumpectomy plus radiotherapy extended to the axilla in case of palpable nodes (WLRT) in 45 patients and wide lumpectomy alone in 221 patients. Postoperative tamoxifen was given to 251 patients and chemotherapy to 31. Mean follow-up was 54 months. Relapse free survival was similar at 5 years in the three groups (80%); at 10 years it was 80.8% in QUART, 61.3% in WLRT, 51.7% in WL. Locoregional recurrence, as first failure, occurred in 1.4% QUART, 6.5% WLRT and 15.2% WL. In our experience compliance with surgical day-hospital regimen was excellent, while postoperative radiotherapy created some problems, mainly among oldest patients. We support the role of radiotherapy for its positive impact on local control.