Tumori Journal

The aim of the study was to evaluate mortality lung cancer trends, as an indicator of female smoking trends, in women resident in different urbanization areas.

Data on the 5,782 female lung cancer deaths that occurred in Tuscany, Italy, during the period 1987–2002 were analyzed, using age-period-cohort models by areas at different urbanization levels. Trends were examined with a log-linear regression model, calculating the yearly estimated percent change. Empirical bayesian estimators of the ratios between observed and expected deaths by municipality were calculated for the most recent period and mapped.

The age-adjusted lung cancer mortality rates increased from 1987 to 2002: estimated percentage change values were equal to 24.5% in the urban areas (P <0.001) and 17.2% in the rural areas (P = 0.023). The age-period-cohort model analyses showed a statistically significant drift and non-linear cohort effects. The higher risk was observed for the birth cohort of women born around 1955 (RR, 5.25; 95% CI, 2.83–9.72). In the rural areas, no significant effects were observed, and the age model showed the best fit. In recent years, the risk appeared concentrated in 9 Tuscan municipalities, accounting more than 35% of the female urban population.

The observed significant cohort effect in the age-period-cohort analyses for the urban areas reflects the social impact of living in these areas to induce smoking-related disease like lung cancer in women. The risk appeared particularly relevant in more recent and urbanized generations (women born around 1955), thereby suggesting urgent effective campaigns against smoking, gender dedicated, especially in urban areas.

Automated reading of smears is increasingly used in cervical screening, and quality control procedures to check its performance are required. The aim of the present study was to evaluate the usefulness of rapid review of all smears coded as “no further review'’ (NFR) by the AutoPap system as a quality control procedure.

From 2002–2005, 153, 269 smears were processed by AutoPap at the Centro per lo Studio e la Prevenzione Oncologica of Florence, Italy, and 24,503 (15.9%) were coded as NFR. All NFR smears underwent immediate rapid review by expert readers.

Sixty-five of 118 NFR cases reviewed as ASCUS-R complied to recommended 6 months cytology, and 25 of 30 NFR cases reviewed as ASCUS-SIL or more severe accepted immediate colposcopy. As a result of such assessment, one single case of microinvasive carcinoma was detected in a woman aged 34 years: NFR smear had been reviewed as AGCUS, was followed by repeat AGCUS cytology and repeat negative colposcopy, and finally underwent conization.

NFR report at AutoPap was associated with an extremely high negative predictive value, which might suggest using AutoPap as a primary screening tool, with NFR report prompting a “return to screening'’ recommendation. Rapid review of NFR smears is not recommended as a quality control measure for the negligible yield of highgrade lesions detected.

Gastrointestinal stromal tumors (GISTs), although rare, are the most common mesenchymal neoplasms affecting the gastrointestinal tract. We present our experience in the treatment of localized and metastatic disease and a review of literature.

Nine patients were observed from April 2002 to July 2004. Eight tumors were in the gastric area and J was in the small bowel. In 5 cases, complete surgical removal was performed, and none of these patients underwent adjuvant therapy. The remaining 4 cases, with locally advanced or recurrent disease, were treated with imatinib.

The patients with localized disease treated only by surgery did not relapse. In the patients with locally advanced or metastatic disease treated by imatinib, we observed 3 partial responses, and one case was not assessable because he had no measurable disease. In 2 of 3 responders, it was possible to perform a new radical surgery.

Our series is too small to draw any conclusion. According to our review of the literature, surgery remains the standard treatment for non-metastatic GISTs. Imatinib mesylate represents a major breakthrough in the treatment of advanced GISTs and is the first effective systemic therapy for the disease.

To assess the activity and tolerability of the combination of mitomycin C and capecitabine in patients with metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens.

We retrospectively reviewed 28 patients with pretreated advanced colorectal cancer who had been treated with mitomycin C, 6 mg/m² on day 1, and capecitabine, 1,900 mg/m² on days 1–14, every 3 weeks. Tumor assessment was performed every 3 cycles, toxicity assessed at each cycle.

Main patient characteristics were median age, 61 years (range, 35–73); male/female ratio, 16/12; single metastatic site involvement, 5/28 (18%); ≥3 metastatic sites, 10/28 (36%). Ninety-six courses of therapy were given (median number, 3; range, 1–9). Twenty-six patients were assessable for response, and all were assessable for toxicity. There was 1 partial response (4%) and 12 had stable disease (43%). Median time to progression was 2 months (range, 1–9) and median overall survival was 6 months (range, 1–29+), with a 1-year overall survival rate of 25%. The regimen was very well tolerated without significant hematological toxicity.

Our results are disappointing. Despite the good safety profile, they do not support further investigation or the routine use of this regimen in this setting.

Irinotecan is a standard option for relapsed/refractory advanced colorectal cancer. Although in a recently reported, randomized trial it was found that a regimen of irinotecan once every 3 weeks was associated with a lower incidence of severe diarrhea than with weekly treatment with similar efficacy, there is no evidence in the literature that suggests the optimal dosing strategy for the drug, along with treatment efficacy and safety, following 5-fluorouracil/oxaliplatin-based chemotherapy in elderly patients. A phase II study has reported significantly reduced toxicity when irinotecan was administered once a week for 2 weeks, followed by a week rest.

From January 2004 to April 2005, we analyzed, retrospectively, our data on single-agent irinotecan as a second-line chemotherapy in elderly patients (≥70 years) with advanced colorectal cancer. Twenty-three patients were evaluated. CPT-11 (80 mg/m²) was given as a 60-min intravenous infusion in repeated 21-day courses comprising weekly treatment for 2 consecutive weeks followed by a 1-week rest. Tumor measurements were obtained after every third course of therapy. Toxicity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, version 2.

The median number of treatment courses received per patient was 4 (range, 1–8). All patients were assessable for toxicity and 21 for response. The most frequently observed severe toxicities were diarrhea (grade 3, 13%) and neutropenia (grade 3, 30.4%; grade 4, 8.6%). Only 1 case of neutropenic fever occurred. Other hematological and non-hematological toxicities were mild and manageable. Objective partial responses were observed in 3 patients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time-to-progression of 4.3 months and a median survival of 8.3 months.

A weekly irinotecan administration can induce tumor control in elderly patients with advanced colorectal cancer that has progressed during or shortly after 5-fluorouracil/oxaliplatin-based chemotherapy. However, a careful monitoring of hematological toxicity and special instructions to prevent and manage diarrhea are mandatory in this setting of patients.

The aim of the present paper was to study the role of irradiation in the atherosclerotic process in patients affected by Hodgkin and non-Hodgkin lymphoma.

We studied 84 subjects, 42 with Hodgkin or non-Hodgkin disease and 42 controls. All 42 cases had been irradiated and were comparable in terms of risk factors for atherosclerosis. All 84 subjects underwent echo-color Doppler of the arterial axis (carotids, abdominal aorta, and femoral arteries), and the intima-media thickness was measured.

The irradiated cases had a greater intima-media thickness in the carotid district, even after dividing them according to age and sex; males were affected more than females. The irradiated patients were at greater risk of developing cardiovascular events than the controls.

An echo-color Doppler of the carotid district is advisable in all patients who have been submitted to radiotherapy, and the patients with a significantly greater than normal intima-media thickness need a strict follow-up, and antioxidant or antiaggregant therapy should be considered.

Temozolomide, a novel alkylating agent, has shown promising results in the treatment of patients with high-grade gliomas, when used as single agent as well as in combination with radiation therapy.

In this report we retrospectively reviewed the clinical outcome of 128 consecutive patients with a diagnosis of high-grade gliomas referred to our Institutions from April 1994 to November 2001. The first 64 patients were treated with radiotherapy alone and the other 64 with a combination of radiotherapy and temozolomide (31 with radiotherapy and adjuvant temozolomide and 33 with radiotherapy and concomitant temozolomide followed by adjuvant temozolomide).

Grade 3 hematological toxicity was scored in 9% of 64 patients treated with radiotherapy and temozolomide. No grade 4 hematological toxicity was reported, and the other acute side effects observed were mild or easily controlled with medications. Age, histology and administration of temozolomide were statistically significant prognostic factors associated with better 2-year overall survival. In contrast, we did not observe a significant difference in overall survival between adjuvant and concomitant/adjuvant temozolomide administration.

We report the favorable results of a schedule combining radiotherapy and temozolomide in the treatment of patients with high-grade gliomas. The literature data and above all the findings of the phase III EORTC-NCIC 26981 trial suggest that actually the schedule can be used routinely in clinical practice. Further clinical studies, using temozolomide in combination with other agents, are required.

To assess the psychological needs of parents after the death of their child from cancer.

The study comprises a preliminary retrospective phase to identify parents who spontaneously contacted the medical staff, followed by a prospective phase in which families were contacted by telephone and were invited to a meeting.

The retrospective study demonstrated that more than 50% of the families spontaneously sought contact with the department. In the prospective study, 17 families were contacted and the majority of them subsequently decided to come to the department for a talk.

Our experience shows that parents have a strong need to have further contact with the team that took care of their children for months. In the process of coping with bereavement, anxiety and depression are common and not necessarily pathological, though there may be psychopathological reactions that can interfere with the parents’ quality of life.

The aims of this study were to assess the clinical utility of circulating preoperative HER-2 extracellular domain p105 detected by enzyme immunoassay (ELISA), to compare the tissue expression of HER-2/neu determined by immunohistochemistry (IHC), to correlate prognostic factors including tumor size, nodal involvement, and hormone receptor status, and to analyze the prognostic significance of the marker in relation to clinical outcome as measured by disease-free and overall survival.

In this study, we enrolled 108 consecutive patients with breast carcinoma, and obtained serum samples and frozen tumor tissues. We compared them with 57 women with fibroadenoma and 63 healthy women as controls.

Univariate ANOVA analysis showed no relationship between HER-2/neu in tissue and serum. Preoperative serum levels of p105 were significantly higher in breast cancer patients than in women with benign disease or healthy women. Concerning the correlation between p105, HER-2/neu tissue expression, and the other prognostic factors, a statistically significant correlation between high serum p105 levels and ER-negative status in breast cancer patients was found. Kaplan-Meier analysis confirmed that patients with positive HER-2/neu tissue expression had a significantly shorter survival than those with negative expression. Analysis with the Cox model demonstrated that tumor size was the only significant independent prognostic factor.

This research failed to demonstrate a relationship between preoperative tissue overexpression and circulating HER-2/neu, suggesting that p105 does not represent a valid alternative to predict a worsened prognosis in breast cancer, but it could be a diagnostic marker to discriminate healthy subjects from breast cancer patients.

Primary and secondary liver tumors are associated with poor prognosis. Neopterin is an indicator of systemic immune activation, and increased neopterin concentrations have been associated with poor prognosis in a wide range of malignant tumors.

Urinary neopterin was determined by high-performance liquid chromatography in 154 patients with primary and secondary liver tumors. The survival of different groups of patients was compared by log-rank test, and Cox regression was used for multivariate analysis.

Urinary neopterin was significantly increased in patients compared to controls. A statistically significant correlation was observed between urinary neopterin and age of the patients, hemoglobin concentration, mean erythrocyte volume and peripheral blood leukocyte or platelet count. In univariate analysis, urinary neopterin below 214 μmol/mol creatinine, peripheral blood leukocytes below 8 x 10⁹/L, hemoglobin equal to or above 125 g/L, no extrahepatic tumor, stage of liver involvement, and colorectal, breast or ovarian primary were significant prognostic factors for survival. In multivariate analysis, Bengtsson stage, presence of extrahepatic involvement, primary other than colorectal, breast or ovarian carcinoma, peripheral blood leukocyte count and urinary neopterin were independent prognostic factors. Increased urinary neopterin during and at the end of follow-up was also associated with poor prognosis.

Urinary neopterin is increased in patients with liver tumors. Neopterin is an independent prognostic indicator in patients with liver tumors along with Bengtsson stage, presence of extrahepatic disease, primary site and peripheral blood leukocyte count.

Thyroid transcription factor (TTF-1) is a tissue-specific transcription factor expressed in the epithelial cells of thyroid and lung. The aim of this study was to evaluate the relationship between the expression of TTF-1 and clinicopathological parameters in pulmonary adenocarcinoma and adenosquamous carcinoma.

Resection material of pneumonectomies and lobectomies of 39 patients was retrospectively examined. Twenty-eight patients were diagnosed with adenocarcinoma and 11 with adenosquamous carcinoma. Tumors were classified into 3 groups: a strongly positive group (++) with ^‡50% tumor cells positive for TTF-1; a weakly positive group (+) with 1–49% positive tumor cells; and a negative group (-) with less than 1% or no positive tumor cells. Analysis was performed with Kaplan-Meier estimates and log-rank tests.

Staining for TTF-1 was negative in 10 cases. There was focal staining in 9 cases, while there was diffuse staining in 20 (51%) cases out of 39, and 15 (75%) of these were adenocarcinomas. There was a statistically significant association between TTF-1 and lymph node metastases (P = 0.029). No relationship was found between TTF-1 positivity and disease-free and overall survival.

TTF-1 expression may be a predictor of lymph node metastases. Additional work in a larger group of patients is needed to better assess the utility of this marker.

A meta-analysis of diagnostic test performance was conducted to compare the results of relevant studies reporting diagnostic accuracy values for mediastinal staging in patients with non-small cell lung cancer (NSCLC). This paper deals with the two most accurate imaging techniques currently in use: positron emission tomography (PET) with FDG and computed tomography (CT). A statistical pooling method was used to perform a quantitative meta-analysis aimed at demonstrating the potential advantage of one of these two methods.

Studies in all languages published between 1998 and 2005 that examined the use of FDG-PET and CT for mediastinal staging in NSCLC patients, enrolled at least 18 participants, and provided enough data to allow calculation of sensitivity and specificity rates were considered eligible for the quantitative meta-analysis. Statistical methods to pool the overall estimates of sensitivity and specificity and to compare the discriminant power of PET and CT were discussed and used.

Of the 13 studies included in the analysis, 12 reported greater accuracy of FDG-PET than CT in detecting mediastinal lymph node metastases. The sensitivity of FDG-PET ranged from 50% to 100%. The estimate of the overall sensitivity was 0.83% with 95% CI (0.749–0.913). Specificity ranged from 79% to 100%, with an overall estimated specificity of 0.87% with 95% CI (0.80–0.95). For CT, the sensitivity and specificity ranged from 50% to 97% and 58% to 94%, respectively; the overall estimate was 0.68% with 95% CI (0.582–0.788) and 0.76% with 95% CI (0.668–0.859). The summary receiver operating characteristic (SROC) approach was used to assess the superior diagnostic accuracy of one of the two methods. The areas under the two SROC curves were AUC_PET = 0.909 vs AUC_CT = 0.794.

Numerical and visual results of the meta-analysis of recent relevant reports agreed that FDG-PET is more accurate than CT in identifying mediastinal lymph node metastases in non-small cell lung cancer.

To analyze the procedural difficulties in the placement of metal stents in stenoses of the digestive tract and optimize the technique.

Twenty-nine patients with digestive tract stenoses were treated from January 1999 to December 2004. In 14 cases the stricture was anastomotic (9 colorectal, 3 esophageal, 1 gastroesophageal and 1 gastrojejunal), in 13 esophageal, in 1 gastric and in 1 duodenal. The stenosis was due to scarring in 5 patients and was malignant in 24 patients (primary in 17 cases and secondary in 7 cases).

The procedure achieved technical success in all cases but 2. For each of the different segments the technical difficulties and the adopted procedural solutions were analyzed.

The interventional radiology approach yielded results comparable to those reported for the endoscopic method and was always well tolerated. The need to rely on materials mostly designed for endoscopic use can make radiological use difficult in some cases.

Phyllodes tumor of the breast with osteosarcomatous differentiation is rare and very little is known about its molecular profile.

An immunohistochemical panel with 37 primary antibodies including cytokeratins, mesenchymal markers, key regulators of the cell cycle, oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors was performed on a formalin-fixed paraffin-embedded sample of phyllodes tumor with osteosarcomatous differentiation in a 49-year-old woman.

Antiapoptotic stimuli (survivin) predominated in sarcomatous cells. Antiproteolytic stimuli (TIMP-1, TIMP-2 and PAI) were preponderant in all cells, a surprising fact in view of the aggressiveness of the neoplasm. The immunoprofile of the osteoblastic and stromal cells was quite similar, except for c-erbB-3, c-myc, cyclin D1 and p21. Both exhibited positive cells for actin, MyoD1 and GFAP.

Our results suggest that this osteosarcoma may have originated from metaplasia of stromal cells that underwent a malignant change.

Acute liver failure is a rare complication of metastatic liver disease with a high mortality. Recognition of malignant infiltration of the liver as the cause of acute liver failure could be a diagnostic challenge.

The medical files of 5 patients with acute liver failure due to metastatic liver disease collected over a 4-year period (1997–2000) in our department were reviewed.

No patient had a past history of cancer. The interval from jaundice to encephalopathy ranged from 7 to 12 days (median, 10). Physical examination revealed hepatomegaly and deep jaundice in all patients. AST elevation ranged from 147 to 1870 IU/L (median, 716 IU/L) and ALT elevation from 74 to 556 IU/L (median, 138 IU/L). All patients died within 4–14 days (median, 7) of admission. None had papillary edema or decerebrate posture before death. Four patients had concurrent renal impairment. Liver imaging studies in 2 of the 5 patients were nondiagnostic and the malignant liver infiltration was confirmed postmortem. Liver histology in all cases showed massive tumoral infiltration of the hepatic sinusoids with diffuse replacement of hepatocytes. The primary tumors were colon, gastric, small cell lung, pancreas and cancer of unknown origin.

Malignant infiltration of the liver should be taken into account in the differential diagnosis of rapidly progressive liver failure. Although effective chemotherapy has improved the survival of patients with metastatic liver disease, there has been no change in the course and outcome of acute liver failure due to malignant infiltration of the liver over the last 2 decades. A proper diagnosis by liver biopsy is mandatory to prevent such patients from being considered for liver transplant.