Post-menopausal hormonal therapy and gallbladder cancer risk

The relation between post-menopausal hormone replacement therapy (HRT) and gallbladder cancer was analyzed in women above age 45 years, using data of a case-control study conducted in Italy between 1985 and 1997, on 31 incident, histologically confirmed cases and 3,702 controls in hospital for acute, non-neoplastic conditions. The multivariate odds ratio (OR) was 3.2 (95% confidence interval: 1.1-9.3) for those who had ever used HRT and the OR tended to rise with longer duration. Although based on small numbers, due to the rarity of the disease, these findings provide the first direct epidemiological evidence of an association between HRT and gallbladder cancer.     

Oesophageal adenocarcinoma: A paradigm of mechanical carcinogenesis?

Incidence of adenocarcinoma of the oesophagus and gastric cardia is increasing in most developed countries and strongly associated with obesity and male gender. An underlying increase in the prevalence of gastro-oesophageal reflux has generally been postulated. We suggest that the increase in frequency of reflux and the 2 associated forms of cancer can be explained by growing abdominal pressure brought about by increasing central obesity, most common among men, and sedentary lifestyle, including car use. Abdominal pressure is further accentuated mainly in men by the shift in Western male dressing towards the general use of belts.     

Concurrent boost radiotherapy as preoperative treatment for locally advanced rectal carcinoma: a new beam arrangement

PURPOSE: To describe a new beam arrangement for preoperative concurrent boost radiotherapy in locally advanced rectal carcinoma. MATERIAL AND METHODS: Three different volumes, ie posterior pelvis, total mesorectal space, and gross tumor volume plus 2 cm, are selected to receive radiation doses of 47 Gy, 51 Gy, and 54 Gy, respectively, in 24 fractions. There are two prerequisites for the use of such a radiotherapy schedule: complete displacement of the small bowel outside the boost volume, and horizontal positioning of the rectal long axis. Both conditions can be attained by patient positioning on a new device, the "Up-Down Table" (UDT). The dose gradient between the three volumes is realized with two daily arc rotation fields with an isocenter that is different from the three additional multileaf collimator pelvic fields (postero-anterior + 2 laterolateral). RESULTS: The treatment data are reported according to the ICRU 62 criteria. A comparison was made between concurrent arc rotation and concomitant static boost techniques. CONCLUSION: The new beam arrangement, with the use of the UDT, allows to administer different radiation doses to three volumes with different tumor cell density in order to obtain the same probability of local response in all target volumes without increasing the toxicity.     

Peripheral paraneoplastic neuropathy,an uncommon clinical onset of sigmoid cancer. Case report and review of the literature

A case of a 76-year-old man presenting with weakness of the lower legs and bilateral steppage gait is described. Neurological examination revealed a sensorimotor neuropathy with axonopathy and myelinic aspects. At the time of the diagnostic workup an episode of rectal bleeding occurred. Colonoscopy demonstrated an exophytic cancer of the sigmoid colon at 40 cm from the anal verge. At surgery the tumor adhered to the ileum, so a left hemicolectomy and ileo-ileal resection were performed. Tumor stage was Dukes' B, Jass III, Astler-Coller B2, T3N0M0. The patient underwent postoperative chemotherapy and was followed for the past three years. At present he is free of disease and the neuropathy has completely regressed without any dedicated therapy. As reported in the literature the appearance of a paraneoplastic neurological syndrome (PNS) may be the first sign of a malignancy that is occult at the time of clinical presentation. The most widely supported theory about its etiology is that of an autoimmune origin. The paraneoplastic neurological syndrome is considered to be at a point of intersection between tumor immunology, autoimmune neurological disease, and basic neurobiology. Previous experience has resulted in a pathogenic model and in a definition of a group of autoantibodies related to the disease. Small cell lung cancer (SCLC) is the neoplasm most frequently associated with PNS; other malignancies include lymphomas and various hematological malignancies. Some authors reported also that the percentage of patients with a high titer of neuronal autoantibodies is small and several of the autoantibodies are present at low levels without any accompanying clinical manifestation. In a clinical retrospective study of the Mayo Clinic Group 115,081 patients were examined over the period 1984-1993 and only 58 patients (0.05%) could be defined as being affected by a paraneoplastic neurological syndrome. Only five of these patients had colon tumors. The number of patients is so small and so widely scattered among publications that no statistical analysis is possible. Probably the only possibility for early identification of such a syndrome is a high degree of suspicion. In fact, these patients are usually first admitted and studied in a neurological unit, and the diagnosis of a tumor-associated disease is a delayed event.     

Tumor microenvironment: what have we learned studying the immune response in this puzzling battlefield?

Recent developments hallmark the progress in the understanding of tumor immunology and related therapeutic strategies. The administration of interleukin-2 (IL-2) to patients with cancer has shown that immune manipulation can mediate the regression of established cancers. The identification of the genes encoding cancer antigens and the development of means for effectively immunizing against these antigens has opened new avenues for the development of active immunization of patients with cancer. However, an efficient immune response against tumor comprises an intricate molecular network still poorly understood. Only when the code governing immune responsiveness of cancer will be deciphered, new therapeutic strategies could be designed to fit biologically defined mechanisms of immune rejection of cancer. In this review, we propose that the mechanisms regulating tumor rejection in response to vaccination will be more efficiently identified by following the evolution of treatment induced events within the tumor microenvironment taking advantage of recently developed technological tools. As a model, we will discuss the observed immune response to tumor antigen -specific immunization and its relationship with the systemic administration of IL-2.     

An estimate of prostate cancer prevalence in Italy

Estimates of the total number of men with a previous diagnosis of prostate cancer in Italy range from 55,000 to 135,000. This wide range of variation is largely due to uncertainties on the number of protein-specific antigen-detected, asymptomatic cases. The number of clinically detected cases, including cases with advanced disease, is less subject to uncertainty, with reasonable estimates ranging from 45,000 to 60,000.     

Weekly paclitaxel in metastatic breast cancer patients: a phase II study

AIMS ANID BACKGROUND: Paclitaxel, a microtubule inhibitor, is one of the most active drugs in metastatic breast cancer. A weekly schedule, at a median dose-intensity of 91 mg/m2, is effective and has less side effects than a 3-week schedule. In this phase II study, we evaluated the toxicity and the activity of weekly 1 hr paclitaxel infusions in metastatic breast cancer patients. STUDY DESIGN: Between February 1999 and February 2001, 26 patients with metastatic breast cancer were treated with weekly paclitaxel (60-90 mg/m2/1 hour iv infusion/weekly). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, paclitaxel was stopped after 6 months of therapy. RESULTS: At a median follow-up of 18.7 months (range, 6.8-30.8), all patients are assessable for response and toxicity. We obtained 8 partial responses (30.8%), 8 stable disease (30.8%) and 10 disease progression (38.4.%). The overall response was 30.8% (95% CI, 13.1-48.5). The median duration of response was 7.6 months (range, 1.8-12.4); median time to progression was 4.86 months (range, 1.4-12.4); median overall survival was 9.9 months (range, 1.7-29.2+). Treatment was well tolerated. Hematological toxicity was mild and only one patient developed grade 3 anemia. Two patients experienced grade 3 cardiovascular toxicity; both had received anthracycline-based regimens. CONCLUSIONS: In our experience, weekly administration of paclitaxel shows a substantial degree of activity even in pretreated metastatic breast cancer patients. The toxicity profile is favorable.