
Research article
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Breast cancer is the most important malignant neoplasm affecting women in Western countries. An increasing number of women undergo regular medical checkups, especially during the first years following the diagnosis. Therefore, from the health planning point of view, it is essential to have prevalence measures to furnish estimates for the demands that the health care system could possibly undergo.
By means of PREVAL, a computerized program, breast cancer prevalence has been measured in the Varese province using incidence and follow-up data from the Lombardy Cancer Registry (LCR).
During the 1986–1988 period, breast cancer prevalence for patients alive within 10 years from diagnosis was about 625 per 100,000 resident women. Of these, 54% were over 60 years and 9% were under 45 years of age. Patients alive within 2 years from diagnosis were about 200 per 100,000 residents; considering the 1978–1980 period, patients alive within 2 years from diagnosis were just 140 per 100,000 residents. This dramatic increase in breast cancer prevalence is present also for long-term survivors (i.e. patients alive at 10–13 years from the diagnosis). Extrapolating breast cancer prevalence measured in the Varese province to the whole Lombardy region, the expected number of prevalent cases alive within 10 years of the diagnosis, presently living in Lombardy, would be 27,500. LCR's breast cancer prevalence figures were compatible with available data provided by the Finnish Cancer Registry.
Owing to aging of the population, the improvement in survival and the increasing incidence, the number of prevalent cases will increase. This phenomenon has and will have great importance for the health planning.
To review false-negative or underreported (reactive changes, squamous or glandular atypia) smears performed in women developing histologically proven CIN2 or more severe lesions within 24 months and evaluate error causes. The study setting was the Florence District cervical cancer population-based screening: about 60,000 women age 25–60 years screened per year.
118 false-negative or underreported cases were identified at screening files-cancer Registry matching, and the original smears were reviewed by six independent readers to judge smear adequacy and error type.
Sampling errors (reported as inadequate, negative or less severe than CIN1 at review) accounted for 74% and screening/interpretation errors (reported as CIN1 or more severe at review) accounted for 26% of studied cases. Screening/interpretation errors were more likely ascribed to misinterpretation and underreporting than to mis-perception of cellular abnormalities.
Quality control should above all address the problem of sampling adequacy. Due to the rarity of misperceived abnormalities (true screening errors), manual or automated rescreening of negative smears would not be an effective procedure for quality control.
The Fenretinide (4-HPR) Breast Cancer Study is a randomized multicenter clinical trial originally designed and conducted by the investigators of the Istituto Nazionale Tumori of Milan. The study is sponsored by the National Cancer Institute of Bethesda and by the Italian National Research Council. The trial was designed to evaluate the effectiveness of the synthetic retinoid 4-HPR, at a dose of 200 mg per os every day for 5 years, in reducing the incidence of contralateral breast cancer in a population of patients previously operated on for breast cancer. Between 1987 and 1993, the Istituto Nazionale Tumori of Milan and 9 other collaborating Centers enrolled 2,972 women between the ages of 30 and 70 years who had been previously operated on for T1-T2 N- M0 breast cancer. This paper describes the rationale, design, methodology, organization, data management, statistics and accrual of the participating population.
Despite the introduction of innovative techniques in radiotherapy (RT) delivery, no significant improvement in survival has been achieved in the last decades. Concurrent chemoradiation therapy (CRT) is one of the several avenues being explored to improve the results.
Twenty-eight women with locally advanced squamous cell carcinoma of the uterine cervix were treated with CRT comprising a combination of external and intracavitary RT, along with 3 cycles of 5-fluorouracil (5-FU) and carboplatin. Toxicity, pelvic control rate and disease-free survival achieved in this group of patients were compared in a case-control study with those of a group of 28 patients with similar clinicopathologic characteristics treated with radical RT alone at our institution.
CRT was well tolerated, with 97% of the patients completing the protocol as planned. Acute toxicity, primarily hematologic, was significantly (P=0.05) higher in the cases than in the controls (25% vs 3%). One treatment-related death occurred in a stage III patient in the CRT group. The median follow-up was 55 months (range, 20–156) in the RT group and 20 months (range, 14–46) in the CRT group. Pelvic control rate, disease-free survival and overall survival were not significantly different in the two groups. Estimated 5-year survival rate was 70% and 66% respectively for the RT and CRT group.
Concomitant carboplatin/5-FU and radiotherapy is a safe and tolerable means of treatment for locally advanced cervical cancer. In our study, however, concurrent CRT did not result in a significant improvement in pelvic control rate or survival compared to standard conventional radiotherapy.
The use of high-dose chemotherapy followed by hematopoietic rescue is increasing worldwide for solid tumors. Several studies have suggested that the period of absolute neutrophil count (ANC, <500/ml) may be shortened in patients who receive peripheral blood progenitor cells (PBPC). To estimate the clinical value of granulocyte-colony-stimulating factor, we examined a cohort of 26 consecutive patients with advanced breast cancer who received one or two cycles of high-dose chemotherapy with PBPC rescue with or without filgrastim. Thirty-five courses of high-dose ICE (ifosfamide, carboplatin, etoposide) chemotherapy were administered and evaluated. All patients received PBPC rescue. Sixteen patients (21 courses) received subcutaneous filgrastim (5 mg/kg) following PBPC infusion. Recovery to ≥ 500 ANC occurred at a median time of 7 days post PBPC infusion among patients who received filgrastim versus 10 days among patients who received standard support care only (P<0.01). The administration of filgrastim was not associated with a reduction in the duration of hospitalization, in the total number of days on nonprophylactic antibiotics, number of red blood cell transfusions, time to platelet engraftment, or number of febrile days. This could be the consequence of the high hematopoietic cell dose administered in the study. Therefore, any effect of filgrastim was probably masked by the use of a large number of PBPC. Larger prospective randomized studies, specifically focused on the utility of the administration of growth factors following high-dose chemotherapy and PBPC rescue, may be warranted to know whether the administration of filgrastim after PBPC transplantation is really necessary.
Radiation has been shown to affect the uptake of micromolecules by the tissues within the radiation fields. We measured tumor drug uptake throughout a course of radiotherapy for stage III non-operable non-small-cell lung cancer (NSCLC).
Thirty patients were treated with radiotherapy consisting of 15 fractions of 300 cGy given over 3 weeks. They were divided into groups of 2. At 1.5 hr before a given fraction of radiotherapy, one group was given iv a bolus of 6 mg/m2 CDDP (cis-diamminedichloroplatinum). Between 1.5 and 2 hr after radiotherapy, the patients underwent bronchoscopy, during which a biopsy was taken from the tumor mass. A similar procedure was carried out on a different group of 2 patients at each of the 15 radiotherapy fractions. The amount of platinum in the biopsy sample was measured by atomic absorption spectroscopy and expressed as ng platinum/mg tissue. In another 13 patients, a biopsy was taken before beginning the radiotherapy, and they served as controls.
The quantity of platinum/g of tissue in the patients was 11 ± 4.4 ng/mg tissue. During the course of fractionated radiotherapy, the quantity of platinum/g of tumor varied considerably between radiotherapy fractions. Maximum uptake was at fractions 8 and 9 (92 ng platinum/mg tissue) with the minima during the first few fractions and at fractions 10, 11 and 12 (an average 20 ng platinum/mg tissue).
The cyclical variations in the uptake of CDDP by the tumor tissue during the protracted course of fractionated radiotherapy are probably due to the well-known effects of radiation on vascular function and capillary permeability. The results may have implications for future clinical protocols involving chemo- and radiotherapy for the treatment of the disease.
There is considerable controversy about the distal clearance margin that needs to be maintained beyond the extent of a rectal tumor in order to reduce the risk of local recurrence. We investigated the rate of local recurrence, distant metastases and survival in 87 patients who had undergone radical restorative resection of the rectum for cancer and had been followed up for a median period of over 6 years, and we analyzed the statistical relation (log-rank test for trend) with the length of the distal margin. The distal margin length was divided into three categories: 1 cm, 2 cm, and ≥3 cm.
No significant correlation was found between the length of the distal clearance margin and the oncologic outcome. Taken together, our data suggest that if the resection line distally falls on healthy tissue, there is no need to resect additional rectum in order to achieve a better outcome.
The work was aimed at presenting the indications, techniques and results of the percutaneous transjejunal approach to the biliary tree in patients with hepatobiliary complications due to surgery.
Ten patients, 7 males and 3 females, mean age 50 years (range, 10–62) with hepatico-jejunostomy, who developed cholangitis together with jaundice or bile leakage, underwent this procedure, performed through the anastomotic loop that was not surgically anchored to the abdominal wall in all cases but one. The transjejunal approach was chosen because of non-dilated bile ducts in 3 patients, complex pathologic situations in 5 patients and to avoid complications to a transplanted liver in 2 patients. The jejunal loop was identified using CT, US and fluoroscopy in 4 patients and after its opacification in the remaining 6 (by percutaneous transhepatic or intravenous cholangiography or fistulography).
The procedure was technically and diagnostically successful in all cases. Therapeutic procedures (stenting, dilation, litholysis) were also performed using the transjejunal approach in 7 patients and in 6 of them complete pathological resolution was achieved. There were no complications.
Different pathologies of the biliary tree, in patients with bilio-enteric anastomoses, have been identified and treated by this technique; they were fistulas, anastomotic and/or multiple segmental benign or malignant stenoses of the bile duct, and diffuse intrahepatic lithiasis. The procedure was safe and reliable.
The definitive cure rate for clinical stage I 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.
The metastatic spread of squamous cell carcinoma of the head and neck (SCCHN) to the cervical lymph nodes is a negative prognostic factor in terms of survival. We have used multivariate analysis to identify the possible prognostic significance of a number of clinical and pathological characteristics in relation to possible involvement of the cervical lymph nodes in a series of 396 patients.
396 patients with SCCHN were studied. Variables regarding the patient, the carcinoma and histology were analysed by multivariate analysis using BMDP's PLR programme.
Some variables appear to represent predisposing factors for tumor spread to the lymph nodes: tumor site (supraglottic larynx: P=0.005; base of the tongue: P=0.02; hypopharynx: P=0.02), grading (P=0.001), and a number of histological parameters (lower degree of histological differentiation: P=0.001; vascular permeation: P=0.04; perineural invasion: P<0.05; prevalently plasmocytic infiltrate: P<0.05).
The identification of cases at risk for metastasis can be improved by the assessment of prognostic factors, with a consequent improvement in treatment strategies.
High ferritin serum levels have been reported in patients suffering from various malignancies. The aim of this study was to evaluate the role of ferritinemia in the preoperative diagnosis of ovarian carcinoma.
Between March 1993 and September 1996, 60 patients suffering from ovarian carcinoma were surgically treated at our Department. Their ferritin serum levels were measured preoperatively by a solid-phase, two-site chemiluminescent immunometric assay and compared with those of a group of 60 healthy, age-matched, non pregnant controls.
The mean serum concentration of ferritin was 54.7 ± 7.8 ng/ml (range, 14–135) in healthy controls and 112.3 ± 21.2 ng/ml (range, 9–947) in patients with ovarian carcinoma. The difference was statistically significant (P = 0.005, X2 test = 7.951). Serum ferritin was elevated preoperatively (cutoff ≥ 120 ng/ml) in 18/60 patients with malignancy (sensitivity 30%), whereas the CA 125 levels were above the cutoff in 53/60 patients (sensitivity 88.3%). Only 2/60 women of the control group had ferritin titers > 120 ng/ml (specificity 96.7%). The ferritin levels increased with advancing disease stage; no significant correlation was found between ferritin concentration and neoplastic histology and grading. The mean serum iron levels were also measured preoperatively in patients with ovarian carcinoma and healthy controls. They were 57.2 ± 3.8 and 66.3 ± 2.61 μg/dl, respectively, and the difference was not significant (P = 0.655, X2 test= 0.200).
The present study underlines that although ferritin shows an elevated specificity, its low sensitivity does not suggest any true usefulness as a tumor marker in epithelial ovarian cancer.
Steroid hormone receptors are important parameters to characterize breast tumors. Thus, it is important to evaluate their relationships with factors such as histological type and size of the tumor, axillary lymph node invasion and distant spread, age and menopausal status of the patients, and parameters of tumor differentiation.
The receptor levels observed vary within wide ranges. Therefore, statistically significant differences between different groups of parameters are seldom found. A significant dependence on receptor levels has been observed only for patient age and menopausal status. The parameters clinical stage, tumor size, tumor histology, metastatic involvement and histopathologic grading showed no statistically significant relation with receptor levels. Nevertheless, a relationship exists between all parameters mentioned and the frequency of a positive receptor status. Consequently, receptor status can contribute to define the biological behavior of the disease in specific groups of patients. In individual cases other parameters than the biochemical evidence of steroid receptor binding seem to be more important. We found that data derived from DNA flow cytometric measurements allowed a better recognition of tumor aggressiveness than ER status. In axillary lymph node metastases we usually observed higher receptor levels than in primary tumors, but we did not find an age dependency of ER levels in these metastases.
Silver binding nucleolar organizer regions (AgNORs) were counted in tissue sections and were shown to assist in the distinction between benign and malignant breast lesions. The mean AgNOR counts in fibroadenomas were 1.05 ± 0.85 (n=18), in lobular carcinoma 3.55 ± 0.56 (n=35), and in intraductal carcinoma 4.83 ± 1.20 (n=45). AgNOR counting may provide information on breast cancer prognosis supplementary to that obtained with other methods such as flow cytometric analysis. The AgNOR values in carcinomas were also compared with ploidy and S-phase fractions (S) by flow cytometry. More than 75% of the total cancers with counts above 3 dots per nuclear profile contained aneuploid cells, whereas 20% with counts below 3 contained diploid cells (P < 0.05). Similar trends were noticed with regard to S-phase fractions, which were 45% ± 12.5 and 14% ± 4.5, respectively, for the two groups (P < 0.05). AgNOR counting, flow cytometry and clinical parameters may provide complementary information on breast cancer prognosis.
Carcinomas of the uterine cervix and breast, which have a different etiopathogenesis, are the most common malignancies among Indian women. Between these two cancers a comparative study was undertaken in which serum lipids were assessed along with host immunity. Thirty randomly selected cases each of breast and cervical carcinoma, and 20 matched healthy control women were studied by means of standard procedures. Significantly higher (P < 0.001) mean levels of triglycerides (x = 192.1 mg/dl, SD ± 113.5) and total cholesterol (x = 212.9 mg/dl, SD ± 49.78) were observed in breast cancer as compared to controls or cervical cancer patients. Patients with cervical cancer had low mean values of all lipid fractions. Women with the above malignancies also showed a significantly decreased CD3+ and CD4+ population (P < 0.001), while there was a significant increase in CD8+ cells (P < 0.005) compared to normal controls. Interestingly, a significant relationship (P < 0.05) was observed between CD8+cells and LDL-cholesterol among the cancer patients (r = 0.3652 and r = 0.4298 for carcinomas of breast and cervix, respectively).
Thromboembolic complications are common in patients with cancer and represent the second cause of death in patients with overt malignant disease. The aim of this study was to investigate the activated protein C pathway in cancer.
We studied the coagulation cascade, natural clotting inhibitors, fibrinolytic proteins and resistance to activated protein C in 20 patients with advanced gastrointestinal cancer and 84 volunteers by measuring PT, APTT, fibrinogen, AT III, PC, PS, APC resistance, fibrinolytic system (PLG, ANPL, PAI-1 and t-PA) and activation peptides (D-Dimers, prothrombin 0 fragment 1+2/F1+2).
Laboratory tests confirmed coagulation abnormalities in cancer patients. Fibrinogen, D-Dimers and F1+2 were increased, while t-PA activity was significantly lower than that of controls. APC resistance was higher in cancer patients compared to the control group (55% vs 2%; P < 0.0001). Excess thrombin generation was manifested by increased F1+2 plasma levels in APC-resistant cancer patients. Genetic analyses showed that only one patient with a poor response to APC carried a factor V R506Q mutation in exon 10.
Our findings show a high prevalence of APC resistance in cancer, compatible with an acquired defect in the APC pathway.
We evaluated the frequency of serum antineuronal antibodies in a cohort of 39 neuroblastoma patients and related their presence to clinical features. Twelve patients displayed antineuronal antibodies at immunocytochemistry. Only one of these 12 patients suffered from a clinically overt paraneoplastic syndrome. No significant differences emerged between autoantibody-positive and autoantibody-negative patients in terms of progression-free and overall survival, although when only patients evolving to disease progression were considered, the time interval between diagnosis and progression was slightly longer in autoantibody-positive patients.
Cancer of the appendix was found in a 69-year-old female patient affected by long-standing ulcerative colitis (UC). On histological examination the cancer was a typical cystadenocarcinoma of the appendix. The appendiceal mucosa not invaded by the neoplastic process was normal. Histological examination of the colorectal mucosa did not show dysplasia or cancer. These findings suggest that appendiceal cancer and UC may be unrelated diseases. A surveillance program for early detection of cancer of the appendix in patients with longstanding UC does not seem mandatory.


