Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study.

BACKGROUND: In the USA, about 30 200 well-differentiated thyroid carcinomas were diagnosed in 2007, but the prevalence of thyroid nodules is much higher (about 5% of the adult population). Unfortunately, the preoperative characterisation of follicular thyroid nodules is still a challenge, and many benign lesions, which remain indeterminate after fine-needle aspiration (FNA) cytology are referred to surgery. About 85% of these thyroid nodules are classified as benign at final histology. We aimed to assess the diagnostic effect of galectin-3 expression analysis in distinguishing preoperatively benign from malignant follicular thyroid nodules when FNA findings were indeterminate. METHODS: 544 patients were enrolled between June 1, 2003, and Aug 30, 2006. We used a purified monoclonal antibody to galectin-3, a biotin-free immunocytohistochemical assay, and a morphological and phenotypic analysis of FNA-derived cell-block preparations. Galectin-3-expression analysis was applied preoperatively on 465 follicular thyroid proliferations that were candidates for surgery, and its diagnostic accuracy was compared with the final histology. FINDINGS: 31 patients were excluded because they had small galectin-3-negative thyroid nodules; we did not have data for 47 patients; and one patient with an oncocytic nodule was excluded. 331 (71%) of the assessable 465 preoperative thyroid FNA samples did not express galectin-3. 280 (85%) of these galectin-3-negative lesions were classified as benign at final histology. Galectin-3 expression was detected, instead, in 134 of 465 (29%) thyroid proliferations, 101 (75%) of which were confirmed as malignant. The overall sensitivity of the galectin-3 test was 78% (95% CI 74-82) and specificity was 93% (90-95). Estimated positive predictive value was 82% (79-86) and negative predictive value was 91% (88-93). 381 (88%) of 432 patients with follicular thyroid nodules who were referred for thyroidectomy were correctly classified preoperatively by use of the galectin-3 test. However, 29 (22%) of 130 cancers were missed by the galectin-3 method. INTERPRETATION: Our findings show that if the option of surgery was based theoretically on galectin-3 expression alone, only 134 thyroid operations would have been done in 465 patients; therefore a large proportion (71%) of unnecessary thyroid surgical procedures could be avoided, although a number of galectin-3-negative cancers could be potentially missed. The galectin-3 test proposed here does not replace conventional FNA cytology, but represents a complementary diagnostic method for those follicular nodules that remain indeterminate.

Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Lesions.

Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96; P < 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73-83. ©2017 AACR.

Cytological value of sputum in workers daily exposed to air pollution.

In this study, quantitative modifications of dust cells, siderocytes, Curschmann's spirals and asbestos bodies and qualitative modifications (cellular changes and inflammatory infiltrate) in the sputum of 164 traffic police officers and 218 railway workers, occupationally exposed to environmental pollution, and the sputum of 119 inhabitants of a rural area, were evaluated. The results were correlated with time of exposure and smoking habits. Seventy-three (45%) traffic police officers (TPO), 76 (35%) railway workers (RW) and 29 (24%) of the rural population (RP) were smokers. The sputum, collected over a 3-day period, was smeared on glass slides and stained according to the Papanicolaou, Perl and yellow eosin methods. The results of the qualitative cytological diagnosis revealed a statistically significant difference between the TPO, RW and the RP (p < 0.001). The results of the qualitative and quantitative cytological examinations were not significantly correlated to time of occupational exposure, which was considered to be a continuous variable. The qualitative cytological examination of sputa was not statistically significant for the smoking habits of the TPO and the RP, but was significant for the RW (p < 0.0067). In the TPO, the number of dust cells was higher in smokers, and the relative risk (RR) was 3.95. In the RW, the RR was 2.84. The results of our study revealed that for the RW, the qualitative-quantitative cytological alterations in sputum were due much more to smoking habits than to occupational exposure, while the presence of asbestos bodies correlated with work activity. The qualitative-quantitative cytological examinations of the TPO differed significantly from that of the other two populations.

Prevalence of acetowhite areas in male partners of women affected by HPV and squamous intra-epithelial lesions (SIL) and their prognostic significance. A multicenter study.

BACKGROUND: Estimates for the prevalence of cervical HPV infection vary and are only available for a few populations with regard to male partners. Attention has been drawn to the male role in cancer progression from cervical intra-epithelial neoplasia, but most of the male lesions are subclinical and only visible after acetowhite staining. The prognostic significance of acetowhite areas, of male partners of women affected by HPV and preneoplastic lesions, was evaluated. MATERIALS AND METHODS: A cohort of 3210 male partners of women affected by HPV infection and/or preneoplastic lesion of the lower genital tract was observed from 1987 to 2001. Acetowhite changes were assessed 5 min after the application of 5% solution of acetic acid and biopsies were tested for HPV-DNA by PCR. Patients with HPV lesions underwent CO2 laser surgery and follow-up. RESULTS: Of the 3210 male partners, 39.12% exhibited clinical HPV lesions and 3.64% subclinical lesions identified as acetowhite areas. In the group of 117 male partners with acetowhite areas, the HPV-DNA test was positive (HPV 6-11) in 36.75% and negative in 63.24% (p<0.001). No statistical differences were observed between HPV+/- groups regarding their sexual habits. The HPV-positive infection group compared to the HPV-negative group showed a statistically significant difference for CO2 laser surgery (p<0.001). CONCLUSION: The acetic acid test can give false-positives and is not a specific indicator of HPV infection, and thus the limited efficacy of tests for acetowhite areas was confirmed. The treatment of clinical lesions is necessary. Follow-up represents the major route to the diagnosis of preneoplastic lesions in men and for the prevention of cervical carcinoma in their female partners.

Follow-up of high-grade squamous intra-epithelial lesions (H-SIls) in human immunodeficiency virus (HIV)-positive and human papillomavirus (HPV)-positive women. analysis of risk factors.

BACKGROUND: Human immunodeficiency virus (HIV)-positive women are at high risk of co-infection from human papillomavirus (HPV) and of developing squamous intraepithelial lesions of the cervix. MATERIALS AND METHODS: From April 1997 to March 1999, 86 women, affected by high-grade squamous intra-epithelial lesions (H-SILs), were enrolled: 41 were HIV+ (CD4+ count >500/ml) and 45 were HIV-. The diagnosis of high-grade squamous intra-epithelial lesion (H-SIL) was established for each patient by Pap test, colposcopy and guided biopsy. For all samples, the HPV/DNA test was also performed by PCR. The patients' lesions and recurrence were treated by cone biopsy or large loop excision (LEEP). Annual controls were performed for 5 years. RESULTS: A high rate of alcohol and drug use (60.7% vs. 31.4%; p=0.004; 80% vs. 27.5%; p<0.001, respectively) and number of male partners (4.5 vs. 3.0; p<0.001) were found in the HIV+ patients, compared to the HIV- patients. Both groups were HPV+ for high-risk types. No difference was found in the percentage of patients who had received a second LEEP. CONCLUSION: Our findings suggest the treatment of H-SIL in HIV-positive women, for a longer disease-free survival, or a lower risk of developing cervical cancer.

Bisphosphonates and oral cavity avascular bone necrosis: a review of twelve cases.

BACKGROUND: Intravenous bisphosphonates are the current standard of care for the treatment of hypercalcemia of malignancy and for the prevention of skeletal complications associated with bone metastases. Recently, retrospective case studies have reported an association between long-term bisphosphonate therapy and osteonecrosis of the jaws. PATIENTS AND METHODS: The data for twelve patients, referred to either an oral and maxillofacial surgeon or to an oral medicine specialist for the management of clinically apparent chronic oral osteonecrosis of unknown etiology, were reviewed. All had received cancer-related therapy simultaneously with bisphosphonate management. RESULTS: The typical presenting symptoms were pain and exposed bone at the site of a previous tooth extraction. In most patients, the lesions initially occurred after dental extraction or other odontostomatological procedures, while five had a spontaneous event. Biopsy of the involved area showed the presence of necrotic lacunae, with infiltration of lymphocytes and histiocytes. In nine cases, there was histological or cytological diagnosis of suspicious osteomyelitis. No correlation was observed between the intraoral lesions and myelosuppression secondary to antineoplastic therapy. CONCLUSION: Based on the patients' respective histories, clinical presentations and responses to surgical and antibiotic treatments, it appears that the pathogenesis of this osteonecrotic process is most consistent with localized vascular insufficiency. In our opinion, the mechanism by which bisphosphonates compromise bone vascularity may be related to their effect on the osteoclasts. The potent bisphosphonate-mediated inhibition of osteoclast function serves to decrease bone resorption and inhibit normal bone turnover remodeling, resulting in microdamage accumulation and a reduction in some mechanical properties of the bone.

Fractionated ionizing radiation exposure induces apoptosis through caspase-3 activation and reactive oxygen species generation.

BACKGROUND: Radiation therapy (RT) is a well established therapeutic modality for the treatment of solid tumors. In particular, post-operative RT is considered the standard treatment adjuvant to surgery since its ability to prolong median survival of patients with malignant astrocytoma has been shown; nevertheless the ionizing radiation (IR) treatment fails in a considerable number of astrocytoma patients. MATERIALS AND METHODS: Using an ADF human astrocytoma cell line the molecular mechanisms involved in the DNA damage induced by fractionated irradiation (FIR) and single IR treatment have been investigated. RESULTS: FIR and single IR treatment inhibited the growth of the ADF human astrocytoma cell line. FACS analysis revealed that FIR treatment, but not single IR treatment, induced growth inhibition associated with the induction of apoptosis. Apoptosis was related to caspase-3 activation and reactive oxygen species (ROS) generation. ROS formation depends on the up-regulation of the cytochrome P450 enzyme gene. On the contrary, 12.5 Gy induced necrotic cell death up-regulating the HSPD1, HSPCB, HSPCA and HSPB1 genes. CONCLUSION: FIR treatment induced cell death through caspase-3 and ROS-mediated apoptosis.

Myc down-regulation sensitizes melanoma cells to radiotherapy by inhibiting MLH1 and MSH2 mismatch repair proteins.

PURPOSE: Melanoma patients have a very poor prognosis with a response rate of <1% due to advanced diagnosis. This type of tumor is particularly resistant to conventional chemotherapy and radiotherapy, and the surgery remains the principal treatment for patients with localized melanoma. For this reason, there is particular interest in the melanoma biological therapy. EXPERIMENTAL DESIGN: Using two p53 mutant melanoma models stably expressing an inducible c-myc antisense RNA, we have investigated whether Myc protein down-regulation could render melanoma cells more susceptible to radiotherapy, reestablishing apoptotic p53-independent pathway. In addition to address the role of p53 in the activation of apoptosis, we studied the effect of Myc down-regulation on radiotherapy sensitivity also in a p53 wild-type melanoma cell line. RESULTS: Myc down-regulation is able per se to induce apoptosis in a fraction of the cell population (approximately 40% at 72 hours) and in combination with gamma radiation efficiently enhances the death process. In fact, approximately 80% of apoptotic cells are evident in Myc down-regulated cells exposed to gamma radiation for 72 hours compared with approximately 13% observed after only gamma radiation treatment. Consistent with the enhanced apoptosis is the inhibition of the MLH1 and MSH2 mismatch repair proteins, which, preventing the correction of ionizing radiation mismatches occurring during DNA replication, renders the cells more prone to radiation-induced apoptosis. CONCLUSIONS: Data herein reported show that Myc down-regulation lowers the apoptotic threshold in melanoma cells by inhibiting MLH1 and MSH2 proteins, thus increasing cell sensitivity to gamma radiation in a p53-independent fashion. Our results indicate the basis for developing new antitumoral therapeutic strategy, improving the management of melanoma patients.

PRb2/p130, p107 and p53 expression in precancerous lesions and squamous cell carcinoma of the uterine cervix.

The aim of this study was to investigate pRb2/p130, p107 and p53 expressions in precancerous lesions and squamous cell carcinoma (SCC) of the uterine cervix. We evaluated Human Papillomavirus (HPV) testing and typing and pRb2/p130, p107 and p53 expressions (antibody D07) of 48 patients showing low-grade cervical intraepithelial neoplasia (LCIN, 18 cases), high-grade CIN (HCIN, 13 cases) and SCC (17 cases). Paraffin-embedded tissue sections were analyzed for the study. High-risk HPV types were present in 67%, 89% and in 100% of HPV-positive LCIN, HCIN and SCC, respectively (Spearman's correlation coefficient: 0.393, p=0.035). Positive pRb2/p130 expression was detected in 89% of LCIN, 77% of HCIN and in 35% of SCC (p=0.001), whereas diffuse p107 expression was 72%, 62% and 100%, respectively (p=0.024). The results of p53 expression in CINs and SCCs showed values (not statistically significant) comparable with the literature data concerning the antibody D07. For the first time, we tested pRb2/p130 and p107 expressions in CINs and SCCs. We found a progressive decrease in pRb2 expression from CINs to SCCs that suggests an important role of pRb2 in cervical carcinogenesis. Indeed, p107 expression does not seem to be a useful factor. In our opinion, confirmed by the literature data, p53 immunostaining helps to biologically characterize CIN (in particular LCIN) when each case is evaluated separately considering HPV testing/typing.

Accuracy rates of US-guided vacuum-assisted breast biopsy.

A prospective study designed to measure the accuracy of mammography (MRx), ultrasound (US), fine-needle aspiration cytology (FNAC) and one of the most recently introduced techniques, vacuum biopsy (VB), in the diagnosis of breast cancer is reported. A sample of 146 breast lesions on 135 patients were examined. The design of the study made it possible to compare MRx, US, FNAC and VB directly, because it excluded several confounding variables. Statistical indicators--sensitivity, specificity, predictive values (PPV and NPV), false-negative and false-positive rates (FN and FP), suspicious plus indeterminate rate and likelihood ratios (LR)--were calculated. The NPV of MRx and US were remarkably high (92.4% and 97.9%, respectively), confirming previous reports. The complete sensitivity of FNAC was 80%, while specificity was 99.1% and LR of positive tests 88.8. The combined score of FNAC, US and MRx resulted in a good increase in complete sensitivity (97.1%), when compared with the results of the single diagnostic tests evaluated separately. The absolute sensitivity of VB was 97.1% and specificity was 100%. In conclusion, considered together, MRx, US and FNAC appear to be reliable diagnostic procedures and, when they are all negative, the possibility of a cancer is extremely low, although it cannot be completely ruled out. The VB test had the highest absolute sensitivity among all the methods compared. Therefore, this technique could be considered conclusive in diagnostically doubtful cases, avoiding open surgical biopsy.

Gastric mucosa alterations in first-degree relatives of gastric cancer patients.

BACKGROUND: First-degree relatives of gastric cancer patients have an increased risk of developing such neoplasia, and several alterations in gastric mucosa of these subjects have been described. On the other hand, both gastric cell hyperproliferation and abnormalities of adhesion molecules have been involved in gastric carcinogenesis. We studied gastric mucosa alterations in first-degree relatives of gastric cancer patients. PATIENTS AND METHODS: This prospective, case-controlled study enrolled 39 first-degree relatives of gastric cancer patients and 39 matched controls. Biopsy specimens obtained at endoscopy were used to assess epithelial cell proliferation plus E-cadherin and beta-catenin expression by immunohistochemical methods. H. pylori infection was assessed by histology and a rapid urease test. RESULTS: Gastric epithelial cell proliferation values were not significantly different between the patient and control groups. H. pylori infection significantly increased cell proliferation values both in patients and in controls, without a significant difference between the two groups. Moreover, cell proliferation values were significantly higher in cases harboring intestinal metaplasia than in those without it. Alterations of the adhesion molecules were described exclusively in those patients harboring intestinal metaplasia. In detail, a reduction of both E-cadherin and beta-catenin expression was observed in 8 (67%) out of 12 first-degree relatives and in 6 (67%) out of 9 controls with intestinal metaplasia (p = 0.4). These alterations were similarly distributed between H. pylori infected and uninfected cases. CONCLUSION: Our data showed that a family history of gastric cancer itself is not associated with gastric cell hyperproliferation. However, both cell hyperproliferation and alterations of adhesion molecules have been detected in those patients with intestinal metaplasia.

Nail disorders in a woman treated with ixabepilone for metastatic breast cancer.

Ixabepilone (Ix) (BMS-247550) is a potent member of a new class of microtubule-stabilizing cytotoxic agents known as epothilones. In pre-clinical studies, Ix has shown anticancer activity against several cancer types, including paclitaxel-resistant models, both in vitro and in vivo. The major toxicities associated with Ix are myelosuppression, sensory neuropathy and neutropenia. Other minor side-effects include asthenia/fatigue, stomatitis, anorexia, alopecia, skin reaction, hypersensitivity reactions and a fluid-retention syndrome. Although Ix is functionally correlated to taxanes, no previous evidence exists regarding Ix-related nail disorders. Here, we report a case of a 59-year-old woman treated with Ix at 40 mg/m2 day 1 q 21 days who, after 8 cycles of therapy, developed onycholysis and subungual hemorrhagic bullas in the fingernails.

Clinical experience with bevacizumab in colorectal cancer.

Angiogenesis, the process of generating new capillary blood vessels, is a fundamental requirement for normal physiological processes including embryogenesis, reproductive function and wound healing. Angiogenesis is also implicated in various pathological conditions including age-related retinal macular degeneration, diabetic retinopathy, rheumatoid arthritis, psoriasis and cancer growth and metastasis. Vascular endothelial growth factor (VEGF) is one of the best characterized of the pro-angiogenic growth factors, and multiple strategies have been developed to inhibit this pathway. Bevacizumab, a monoclonal antibody developed against VEGF, has shown initial preclinical and clinical activity. This review discusses the critical role of VEGF and summarizes the available data on the use of bevacizumab in colorectal cancer.

Relationship between beta-catenin expression and epithelial cell proliferation in gastric mucosa with intestinal metaplasia.

AIM: To investigate beta-catenin expression in patients with intestinal metaplasia, and to look for a possible relationship between beta-catenin expression and either epithelial proliferation values or Helicobacter pylori (H pylori) infection. METHODS: Twenty patients with complete type intestinal metaplasia were studied. beta-Catenin expression and epithelial cell proliferation in antral mucosa were assessed using an immunohistochemical analysis. H pylori infection was detected by histology and a rapid urease test. RESULTS: Reduced beta-catenin expression on the surface of metaplastic cells was detected in 13 (65%) out of 20 patients. Moreover, in eight (40%) patients intranuclear expression of beta-catenin was found. When patients were analyzed according to H pylori infection, the prevalence of both beta-catenin reduction at the cell surface and its intranuclear localization did not significantly differ between infected and uninfected patients. Cell proliferation was higher in patients with intranuclear beta-catenin expression as compared to the remaining patients, although the difference failed to reach the statistical significance (36+/-8.9 vs 27.2+/-11.4, P = 0.06). On the contrary, a similar cell proliferation value was observed between patients with reduced expression of beta-catenin on cell surface and those with a normal expression (28.1+/-11.8 vs 26.1+/-8.8, P = 0.7). H pylori infection significantly increased cell proliferation (33.3+/-10.2% vs 24.6+/-7.4%, respectively, P = 0.04). CONCLUSION: Both cell surface reduction and intranuclear accumulation of beta-catenin were detected in intestinal metaplasia. The intranuclear localization of beta-catenin increases cell proliferation. H pylori infection does not seem to play a direct role in beta-catenin alterations, whilst it significantly increases cell proliferation.

Clinico-pathological significance of cell-type-specific loss of heterozygosity on chromosome 7q21: analysis of 318 microdissected thyroid lesions.

A careful pathological examination often reveals the presence of different lesions at various stages of tumor progression and invasion, even in those thyroid glands presenting with solitary nodules. Each thyroid lesion is composed of many different cell types, reflecting the marked heterogeneity of normal thyroid tissue. Among the different chromosome regions altered in thyroid tumors, 7q21 appears to be specifically involved in malignant tumors, especially of the follicular type. This study was conducted to analyze the loss of heterozygosity (LOH) pattern at 7q21 in pure populations of cells from each single lesion harbored in surgically removed thyroid glands, and to evaluate its clinical significance. One hundred and forty-two thyroid glands were examined, all showing, as a common trait, a goitrous appearance associated with one single lesion in 114 cases and with more than one in the remaining 28 cases. A total number of 318 lesions was analyzed, consisting of 142 goiters (TG), 48 hyperplasias (TH), 80 adenomas (TA) and 48 carcinomas (TC). Five different types of cells were isolated by laser capture microdissection from each lesion. DNA was analyzed by PCR and polyacrylamide gel electrophoresis in search of LOH affecting five microsatellite markers, D7S660, D7S630, D7S492, D7S657, and D7S689. We detected LOH at 7q21 not only in thyroid malignant tumors but also in benign lesions. Allelic loss occurred exclusively in dark nucleus and eosinophilic cytoplasm cells, commonly observed in the follicular type of lesions. In these types of lesions allelic loss frequency increases along with neoplastic transformation (9% in TG, 41% in TH, 68% in TA and 100% in TC), and is directly correlated with thyroid gland volume as well as with the presence of multiple lesions. The highest LOH rate was observed for D7S492, indicating that the recurrent region of deletion was localized at the corresponding genetic locus at 7q21.2, in the same position where the common fragile site FRA7E was previously mapped. LOH at this locus represents an early event in the development of follicular TC and is associated with intense growth of thyroid glands.

New approaches to prevent intestinal toxicity of irinotecan-based regimens.

BACKGROUND: Irinotecan is a selective inhibitor of topoisomerase I, an enzyme part of the replication and transcription system of DNA. Irinotecan is employed, with different modalities, in the treatment of metastatic colorectal cancer, and recently it has been officially approved in association with fluorouracil (FU) and leucovorin (LV) as a first-line option in metastatic colorectal cancer. RESULTS: One of the problems linked to the administration of this drug is the high intestinal toxicity, which constitutes its dose limiting toxicity (DLT). In routine practice, loperamide is employed as symptomatic drug for the treatment of CPT-11-induced diarrhoea, but is not completely adequate to control the problem. The role of the intestinal bacterial microflora in the pathogenesis of CPT-11-induced intestinal toxicity has been recently discovered. The active metabolite of CPT-11, SN38, is generated from CPT-11 by sieric carboxylesterase, and subsequently conjugated to SN38-G by hepatic UDP-glucuronyltransferase. SN38-G is the inactive metabolite of CPT-11 and is excreted into the small intestine, from which it is eliminated in the faeces. Some studies have shown the ability of intestinal bacterial beta-glucoronidases to transform SN38-G into SN38, causing direct damage to the intestinal mucosa. Thus, alternative strategies such as intestinal alkalinization and anti-cyclooxygenase 2 (COX-2) therapy have been explored. CONCLUSIONS: In this review, we will illustrate the mechanisms which cause the CPT-11-induced diarrhoea and the potential measures available to prevent it.

Human papillomavirus in virgins and behaviour at risk.

Human papillomavirus (HPV) infection is one of the most common sexual transmitted diseases (STDs). We compared two groups of virgins with genital HPV lesions to evaluate the behaviour at risk in the transmission of HPV infection. Partners were also examined. HPV lesions were detected in 88 virgins, who have never had sexual intercourse. This can be due to vertical transmission, fomities and skin-to-skin contact. Many other hypothesis can be proposed to explain HPV genital infection, however, further studies are required.

Giant condyloma acuminatum or buschke-Lowenstein tumor: review of the literature and report of three cases treated by CO2 laser surgery. A long-term follow-up.

Giant condyloma acuminatum or Buschke-Lowenstein tumor (TBL) is a rare disease that arises on the male and female external genitalia. TBL arises from the confluence of multiple condylomata acuminata and it is induced a Human Papillomavirus infection. TBL presents a clinical malignancy, but it is known to be a histologically benign tumor, even if it carries a risk of malignant transformation. It is advisable to treat it early. After a review of the literature, three cases of giant condyloma acuminatum, treated by combined CO2 Laser surgery excision-vaporization and which underwent a long-term follow-up are described.

Testis metastasis as an initial manifestation of an occult gastrointestinal cancer.

Metastatic epithelial malignant tumor involving the spermatic cord and epididymis is rare and the prognosis of these patients is poor. Usually gastrointestinal cancers show diffusion to liver, lung and bone. Several routes by which a colorectal cancer can metastasize to the testis have been reported in literature. Herein we report a case of an occult gastrointestinal cancer with an intrascrotal metastasis in an adult patient with possible spread through the spermatic veins due to primary intestinal carcinoma. In the case of a testicular mass or hydrocele evidence in a patient with an unusual age for primary testis tumor, a diagnosis of metastatic cancer should be considered.

PET scanning evaluation of response to imatinib mesylate therapy in gastrointestinal stromal tumor (GIST) patients.

BACKGROUND: Unresectable or metastatic gastrointestinal stromal tumors (GISTs) exhibit a dynamic clinical course, with no evidence of benefit from any standard cytotoxic chemotherapy and an inevitably fatal outcome. With the introduction of Imatinib, an oral drug able to inhibit the KIT receptor tyrosine kinase, new questions arise regarding our ability to monitor treatment response with conventional methods and optimally manage such patients on treatment with new agents. MATERIALS AND METHODS: Herein we report two cases of patients with a history of GIST in treatment with Imatinib. RESULTS: After 4 weeks from treatment start, CT scan evaluation demonstrated a massive increase in the size of metastatic lesions, but a confirmatory PET excluded, in both patients, the presence of any metabolic activity in the previously known metastatic sites. Imatinib therapy was continued with subjective clinical benefit for 12 further months before a PET scan-confirmed disease progression had occurred in one patient and is still ongoing after 15 months in the other. CONCLUSION: These cases open the obvious question of whether conventional imaging techniques are adequate to assess the response to Imatinib treatment in GIST patients.