Tumori Journal

Data and statistics are presented on cancer death certification in Italy, updating previous publications covering the period 1955-1993.

Data for 1994 and the quinquennium 1990-94 subdivided into 30 cancer sites are presented in 8 tables, including age- and sex-specific absolute and percentage frequencies of cancer deaths, and crude, age-specific and age-standardized rates, at all ages and truncated for the 35-64 year age group. Trends in age-standardized rates for major cancer sites are plotted from 1955 to 1994.

The age-standardized (world standard) death certification rates from all neoplasms steadily declined from the peak of 199.2/100,000 males in 1988 to 186.3 in 1994, and in females from 102.5 in 1989 to 98.6 in 1994. Ever larger was the decline in truncated rates, for males from the peak of 275.1/100,000 in 1983 to 223.2 (-19%) in 1994, and for females from 151.6/100,000 in 1987 to 136.4 (-10%). A major component of the favourable cancer mortality trends in males was lung cancer (accounting for 31,000 deaths in both sexes combined in 1994), whose overall age-standardized rates declined from 60.3 in 1987-89 to 54.6/100,000 males in 1994 (-9%), and from the peak of 96.7 in 1983 at ages 35 to 64 to 72.7 in 1994 (-25%). In contrast, female lung cancer rates have remained stable from 1992 onwards, but have increased from 7.2 to 7.7 at all ages and from 10.6 to 11.0 at age 35-64 between 1985-89 and 1990-94. These different trends in the two sexes reflect the patterns and trends in smoking among Italian males and females.

Cancer mortality trends in Italy over the period 1990-94 were relatively favourable, mainly reflecting the decline in lung cancer rates in males, together with the persistent declines in gastric cancer in both sexes and in cervix uteri for women. Continuous advancements were registered for neoplasms amenable to treatment, essentially testicular cancer, Hodgkin's disease and childhood leukaemias. The major unfavourable trends were observed for non Hodgkin's lymphomas, and require therefore further monitoring, besides a clearer understanding of their determinants. Italy maintains an intermediate level of cancer mortality on a European scale, suggesting that further progress is possible, mostly for tobacco-related neoplasms in males.

Attendance level has been identified as a major determinant of cost-effectiveness of organized screening programs. We tested the effectiveness of 4 different invitation systems in the context of an organized population screening program for cervical and breast cancer.

Women eligible for invitation - 8385 for cervical and 8069 for breast cancer screening - listed in the rosters of 43 and 105 general practitioners (GP), respectively, who had accepted to collaborate in the program, were randomized to 4 invitation groups: Group A - letter signed by the GP, with a prefixed appointment; Group B - open-ended invitation, signed by the GP, prompting women to contact the screening center to arrange an appointment; Group C - letter (same as for group A), signed by the program coordinator, with a prefixed appointment; Group D - extended letter (highlighting the benefits of early cancer detection) signed by the GP, with a prefixed appointment. Assignment to the interventions was based on a randomized block design (block=GP).

Assuming Group A as the reference, the overall compliance with cervical cancer screening was reduced by 39% in Group B (RR=0.61; 95% CI, 0.56-0.68) and by 14% in Group C (RR=0.86; 95% CI, 0.78-0.93); no difference was observed for Group D (RR=1.03; 95% CI, 0.95-1.1). The response pattern was similar for breast screening (Group B: RR=0.71; 95% CI, 0.65-0.76; Group C: RR=0.87; 95% CI, 0.81-0.94; Group D: RR=1.01; 95% CI, 0.94-1.08).

Personal invitation letters signed by the woman's GP, with preallocated appointments, induce a significant increase in compliance with screening. Efficiency can be ensured through the adoption of overbooking, provided that attendance levels are regularly monitored.

Given the incidence of breast cancer, histologic agreement is necessary to select the proper treatment.

Twelve pathologists working in Puglia (Italy) independently evaluated a set of 88 slides of breast lesions. The set included 31 cases which presented difficulties at the moment of first diagnosis (problem cases) and 57 cases without problems (routine cases). Each pathologist was requested to classify lesions according to four categories: A, benign; B, atypical proliferation; C, in situ carcinoma; D, invasive carcinoma. For each case, the definite diagnosis was considered that provided by most of the pathologists (prevalent diagnosis). For the evaluation of degree of agreement, kappa statistics were utilized.

Among routine cases, agreement was observed in 68.4% of cases (38/57) and in 29% of problem cases (9/31). The pair-wise comparison between all participating pathologists showed a good overall agreement, (kappa mean, 0.66; range, 0.57-0.76). The agreement of each pathologist with the prevalent diagnosis was high for invasive (mean kappa, 0.88) and benign lesions (mean kappa, 0.83) followed by in situ carcinoma (mean kappa, 0.64). The lowest value observed was for atypical lesions (mean kappa, 0.25).

The results showed a good overall degree of diagnostic concordance among participating pathologists, all working in the Italian region of Puglia. The findings emerging from the study are comparable to those of other studies performed with selected pathologists specifically specialized in breast pathology. Moreover, the study confirmed the diagnostic difficulties for borderline lesions and the necessity of further investigation for sclerosing lesions with discordant diagnoses.

Disorders of hemostasis in patients with malignancies are based on several mechanisms, such as ability of the tumor to alter the coagulation system by producing blood clotting factors or decreasing their inhibitors by increasing fibrinolysis, and by inducing an alteration of blood vessels in relation to the state of local invasion. We investigated the fibrinolytic system marker alpha2-antiplasmin-plasmin complex (APP) and clotting system marker thrombin-antithrombin III complex (TAT) in patients with breast cancer and compare them with CA 15-3, the most well-known breast cancer antigen.

Plasma levels of APP and TAT and serum level of CA 15-3 were determined in 57 patients with breast cancer (28 in remission and 29 with active breast cancer) and 13 healthy women.

In patients with active breast cancer, plasma APP levels were significantly elevated compared to those of other groups (P<0.05). In addition, we observed a poor but positive correlation between plasma levels of APP and those of CA 15-3 (r=0.24; P=0.038). Plasma TAT levels, which reflect the activation of thrombin, were also significantly elevated in patients with active breast cancer (P<0.01), and there was a significant correlation between CA 15-3 and TAT (r=0.24; P=0.041).

We demonstrated that increased APP and TAT levels might reflect enhanced activation of coagulation and the fibrinolytic system in patients with active breast cancer.

The study was performed to assess the feasibility and activity of an intensive chemotherapeutic regimen as adjuvant treatment for patients with resected gastric cancer at high risk of recurrence (PT₂N_1-2; pT_3-4N_any M₀).

Starting 21 to 28 days after potentially curative surgery for primary gastric cancer, 25 patients received 8 weekly cycles of cisplatin 40 mg/m², 5-fluorouracil 500 mg/m², epidoxorubicin 35 mg/m², 6S-stereoisomer of leucovorin at a dose of 250 mg/m², and glutathione at a dose of 1.5 g/m². From the day after to the day before each cycle of chemotherapy, filgrastim was administered by subcutaneous injection at a dose of 5 μg/kg.

After a median follow-up of 33 months, 80% of the patients were alive and disease-free. Five patients had relapsed: three in the liver, one in the peritoneum and one in the lymph nodes. Toxicity was mild: five patients experienced WHO grade III toxicity (three leukopenia, two thrombocytopenia); no toxic deaths occurred.

Intensive weekly chemotherapy is a feasible postoperative treatment option for patients with resected gastric cancer at high risk of relapse. These data, together with recent results in advanced disease, make this approach of interest for the development of new programs of adjuvant therapy in this setting.

The aim of this study was to investigate whether tamoxifen toxicity and treatment discontinuations differred in the adjuvant versus chemopreventive setting.

At our Institutions 119 postmenopausal breast cancer patients were randomized from August 1987 to March 1995 to tamoxifen only within adjuvant studies (International Breast Cancer Study Group studies VII and IX) and 202 healthy hysterectomized women aged 35-70 years were randomized from November 1993 to May 1996 in a multicenter, double-blind, placebo-controlled chemoprevention study (Italian Tamoxifen Prevention Study). The tamoxifen dose was 20 mg/day for 5 years in all studies. Median age was 66 years (54-85) in the adjuvant studies and 53 years (37-69) in the chemoprevention study. Median treatment duration was 238 and 120 weeks, respectively.

Patients treated within adjuvant studies experienced more hot flashes, vaginal discharge and/or bleeding, bone marrow depression and weight gain than those treated in the chemoprevention study, consistent with the fact that a proportion of women in the latter study were receiving placebo. Temporary discontinuation occurred in 2.5% of patients in the adjuvant studies and in 5.4% of women in the chemoprevention study (difference not statistically significant). Permanent discontinuation was more frequent in the chemoprevention study than in the adjuvant ones (26.7% vs 15.1% - P < 0.05).

In summary, our data show that, although the toxicity of tamoxifen is superimposable in the two settings, a larger proportion of women treated as chemoprevention discontinue treatment spontaneously. Due to the double-blind nature of the chemoprevention study, the impact of the toxicity of tamoxifen upon compliance in the chemopreventive setting cannot be ascertained.

An evaluation of the Bologna Hospital-at-Home (BHH) was undertaken to examine the following aspects: 1) median daily costs of the BHH; 2) delivery of medical services; 3) patient satisfaction with the care received and frequency of requests for transfer to the alternative setting. Delivery of services and patient's satisfaction in the BHH were compared with data collected for a traditional hospital (Ospedale Sant'Orsola Malpighi, Bologna - OSM).

Our analysis was performed as a cost analysis considering two periods of time in 1992 and 1993/94. Included were direct and indirect costs; no intangible costs were found. The patient's perspective was selected for the analysis. The observational study examining delivery of service and quality of life of patients admitted to the two care settings, BHH and OSM, considered patient's clinical history and an interview conducted by the evaluation team 6 weeks after admission to either facility. Data included patient's characteristics, quantity of diagnostic and therapeutic measures, circumstances of life, satisfaction with the care received, and intention for transfer to the alternative setting of nursing. The statistical significance of our assumption of comparable care intensity and better patient quality of life in the BHH was tested by the Pearson Chi-square test.

A survey was carried out of 236 patients treated in the BHH or the OSM. The setting of assistance did not influence the provision of services. The time of “talking to the doctor” was notably higher for BHH than for OSM patients. The analysis of satisfaction showed that 98% of the surveyed BHH patients believed it matched the actual needs. The quality of life was considered to be reduced/bad in 67% of the OSM patients but in only 51% of BHH patients. An opinion was also requested with regard to transfer to the alternative setting of nursing: 47% of OSM patients judged BHH care would be better than traditional hospital. The median daily costs in BHH reached 118,789 Lire (range, 108,569-129,027 Lire, depending on performance status).

Although the economic advantage of hospital-at-home care certainly is important, we would like to stress that better quality and dignity of life should be the main point supporting the idea of hospital-at-home care.

A wide range of methodologies for breast reconstruction is now available. For immediate breast reconstruction we prefer to use implants, whereas reconstruction using autologous tissues, such as transverse rectus abdominis musculocutaneous flaps (TRAMF) and muscular latissimus dorsi flaps, is applied only in selected cases. In contrast, for delayed reconstruction the choice between prostheses and autologous tissue depends on various conditions. The different reconstructive methods can be adopted as a single procedure or as a combination of surgical procedures. Following the issue of legislation defining the new structure of the Italian Health Service, the need to accurately assess the costs incurred for the execution of surgical operations has taken on paramount importance. The aim of the study was to evaluate not only the clinical limits of each surgical technique, but also its cost, in order to optimize the choice of the same procedures, conditions being equal.

The study population included 105 patients who underwent breast reconstruction in the period 1st January 1994-30th June 1995. The reconstructive procedures included 48 immediate implants, 7 immediate TRAMF, 17 delayed implants, 30 delayed TRAMF, and 3 delayed latissimus dorsi muscular flaps.

After data evaluation, we concluded that reconstruction using permanent expandable implants is the most convenient among implant reconstructions for its low global treatment cost. In fact, reconstructive procedures using temporary expanders, which require two surgical operations, have a higher cost than breast reconstruction using permanent expandable implants. Breast reconstruction using TRAMF is the most convenient because it limits the cost of surgical materials and because flap versatility limits the number of modifications on the contralateral breast. In contrast, breast reconstruction using latissimus dorsi flaps has high costs.

There is no balance between price list and effective cost of the different surgical reconstructive procedures, which may be a point of departure to see whether it is impossible to improve the efficiency of the Health Care System and in any case open a debate between the Regions and hospitals to improve the service, keeping it at a good level.

Various histogenetic mechanisms have been postulated to explain the biphasic carcinomatous-sarcomatous appearance of malignant mixed müllerian tumors (MMMTs), but the nature of these uncommon neoplasms is still unclear. Some evidence would suggest that MMMT displays similarities with sarcomatoid carcinoma, a tumor arising in extragenital sites that also features a mixed appearance. To gain further insight into the histogenesis of this tumor, we have studied by immunohistochemistry a case of uterine MMMT showing an extensive rhabdomyosarcomatous component.

A panel of antibodies including reactivity for p53, cytokeratin, vimentin, desmin, muscle actin, epithelial membrane antigen (EMA), myoglobin, type IV collagen, laminin, and tenascin was applied to paraffin tumor sections by means of the avidin-biotin complex technique.

p53 immunoreactivity was observed in approximately the same number of cells in carcinomatous and sarcomatous tissue. The former stained for vimentin, cytokeratin and EMA, while the latter, in addition to expressing vimentin, desmin, muscle actin and myoglobin, also exhibited immunoreactivity for epithelial markers such as cytokeratin and EMA. At the borders between carcinoma and sarcoma the basement membrane pattern, as seen by staining for type IV collagen and laminin, showed interruptions in correspondence with areas of transition between the two tissues. Antibody to tenascin strongly labeled the sarcomatous tissue immediately around carcinomatous elements.

A similar immunoreactivity for p53 in both carcinomatous and sarcomatous components, expression of epithelial markers in the sarcomatous cells, and disruption of the basement membrane profile in areas of transition between carcinomatous and sarcomatous tissue, would all suggest, as has been postulated for extragenital sarcomatoid carcinomas, an origin from a common epithelial clone and an epithelial-to-mesenchymal transformation-based mechanism of development for this MMMT. In addition, these findings provide further analogies between these categories of tumors, supporting a unifying nosological concept for MMMTs and sarcomatoid carcinomas of non-genital tract origin.

The authors report the case of a 23-year-old woman affected by intra-abdominal desmoplastic small round cell tumor (DSRCT) who obtained a complete response to multiagent chemotherapy. DSRCT is a rare, highly aggressive neoplasm generally arising in young people and seldom in females (about 20 cases described in the literature).

The patient underwent surgical resection of a large 15 × 15 cm mass located in the right lower abdominal quadrant, but after only 2 months later, two liver metastasis were noted. Thus, she was subjected to an aggressive antineoplastic treatment consisting of three groups of alternating non-cross resistant multiagent regimens administered every 21 days (cis-platin-etoposide-adriamycin-bleomicin; gemcitabine-ifosfamide-dacarbazine; methotrexate-5-fluorouracilfolinic acid) for a total of 9 administrations.

After one cycle of treatment including the administration of all the three alternated schemes of chemotherapy, a complete disappearance of liver disease was noted. The treatment was relatively well-tolerated and the toxicity was acceptable. At present, after 15 months from diagnosis and 12 months after starting chemotherapy, the patient is disease-free and in good health.

Even though this study regards only a single patient, it is noteworthy because of the rarity of this neoplasm and because of the infrequent complete responses reported in the literature. The efficacy and manageability of the treatment, suggests that both the timing and schedule used could constitute an important therapeutical option for this aggressive and poorly chemo-responsive tumor.