A prospective randomized comparison among SWL, PCNL and RIRS for lower calyceal stones less than 2 cm: a multicenter experience : A better understanding on the treatment options for lower pole stones.

PURPOSE: To prospectively evaluate the efficacy and safety of RIRS, SWL and PCNL for lower calyceal stones sized 1-2 cm. MATERIALS AND METHODS: Patients with a single lower calyceal stone with an evidence of a CT diameter between 1 and 2 cm were enrolled in this multicenter, randomized, unblinded, clinical trial study. Patients were randomized into three groups: group A: SWL (194 pts); group B: RIRS (207 pts); group C: PCNL (181 pts). Patients were evaluated with KUB radiography (US for uric acid stones) at day 10 and a CT scan after 3 months. The CONSORT 2010 statement was adhered to where possible. The collected data were analyzed. RESULTS: The mean stone size was 13.78 mm in group A, 14.82 mm in group B and 15.23 mm in group C (p = 0.34). Group C compared to group B showed longer operative time [72.3 vs. 55.8 min (p = 0.082)], fluoroscopic time [175.6 vs. 31.8 min (p = 0.004)] and hospital stay [3.7 vs. 1.3 days (p = 0.039)]. The overall stone-free rate (SFR) was 61.8% for group A, 82.1% for group B and 87.3% for group C. The re-treatment rate was significantly higher in group A compared to the other two groups, 61.3% (p < 0.05). The auxiliary procedure rate was comparable for groups A and B and lower for group C (p < 0.05). The complication rate was 6.7, 14.5 and 19.3% for groups A, B and C, respectively. CONCLUSIONS: RIRS and PCNL were more effective than SWL to obtain a better SFR and less auxiliary and re-treatment rate in single lower calyceal stone with a CT diameter between 1 and 2 cm. RIRS compared to PCNL offers the best outcome in terms of procedure length, radiation exposure and hospital stay. ISRCTN 55546280.

Kidney cancer focal cryoablation trend: does location or approach matter?

PURPOSE: We evaluated the current indications and surgical and survival outcomes for cryoablation (CA) using either a percutaneous (PCA) or a laparoscopic approach (LCA). We also investigated the ability of the PADUA score to predict the risk of complications and local recurrence. METHODS: A retrospective analysis was performed at two European tertiary referral centers. Parameters analyzed included size, location, approach, operative time, hospital stay, complications, and functional and oncologic outcomes. Univariate and multivariate analyses were performed. An ROC analysis was conducted to evaluate the accuracy of the PADUA score. RESULTS: Eighty patients were included. Mean tumor size was 2.6 cm. PCA was more often performed in posterior (95 vs. 60 %), inferior (72 vs. 32 %), and lateral (87 vs. 55 %) tumors. The global complication rate was 8.75 %, although proximity to the renal sinus resulted in a higher rate (30 vs. 4 %). Mean follow-up was 34 and 23 months for LCA and PCA, respectively. The 5-year recurrence-free survival was 76 and 90 % for LCA and PCA, respectively. Multivariate analysis showed that tumor involvement of the collecting system was predictive of recurrence. Under ROC analysis, PADUA score was a mild predictor for complications (AUC = 0.601) and a good predictor for recurrence (AUC = 0.723); PADUA ≥8 was identified as a cutoff for patients to a higher risk of recurrence. CONCLUSIONS: The percutaneous approach is confirmed to be the preferred CA technique for posterior and lateral tumors. CA in deeper renal lesions and tumors with PADUA score ≥8 might entail a higher risk of recurrence, and closer follow-up should be considered in these patients.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

Management of primary upper urinary tract carcinoma in situ diagnosed by ureteroscopic biopsy: Is bacillus Calmette-Guerin an alternative to nephroureterectomy?

BACKGROUND: Radical nephroureterectomy (RNU) represents the gold standard treatment for upper tract urothelial carcinoma (UTUC); however, attempts have been made to treat upper urinary tract CIS (UT-CIS) conservatively. The aim of this study was to compare the outcome of patients with primary UT-CIS treated in our center by means of RNU vs. bacillus Calmette-Guérin (BCG) instillations. METHODS: This retrospective study included patients with diagnosis of primary UT-CIS between 1990 and 2018. All patients had histological confirmation of UT-CIS in the absence of other concomitant UTUC. Histological confirmation was obtained by ureteroscopy with multiple biopsies. Patients were treated with BCG instillations, RNU or distal ureterectomy. Clinicopathological features and outcomes were compared between RNU and BCG groups. RESULTS: A total of 28 patients and 29 renal units (RUs) were included. Sixteen (57.1%) patients (17 RUs) received BCG. BCG was administered via nephrostomy tube in 4 patients, with a single-J ureteral stent in 5, and using a Double-J stent in 7. Complete response and persistence or recurrence were detected in ten (58.8%) and seven (41.2%) RUs treated with BCG, respectively. Eight (27.6%) RUs underwent RNU, and 4 (13.8%) Rus distal ureterectomy. No differences were found in recurrence-free survival (p=0.841) and cancer-specific survival (p=0.77) between the RNU and BCG groups. CONCLUSIONS: Although RNU remains the gold standard treatment for UT-CIS, our results confirm that BCG instillations are also effective. Histological confirmation of UT-CIS is mandatory before any treatment.

Primary urethral carcinoma: Results from a single center experience.

INTRODUCTION AND AIM OF THE STUDY: Primary urethral carcinoma (PUC) is a rare neoplastic disease arising in the urethra, without any evidence of a previous or synchronous carcinoma of the entire urinary tract. Since rare diseases are often incorrectly diagnosed and managed, the aim of this study was to analyze the experience of a single urology center in the treatment of PUC, focusing on neoplasms arising from the male anterior urethra. MATERIALS AND METHODS: Medical records of patients with neoplasms at the level of the penile and bulbar urethra who presented at our tertiary referral center between January 1988 and December 2018 were retrospectively reviewed. Patients with carcinoma of the prostatic urethra were excluded. The diagnosis was obtained with the aid of urethroscopy and lesion biopsy. Local staging was performed by means of contrast-enhanced MRI in selected patients. Staging was achieved by clinical examination, ultrasonography, and CT scan. Radical surgery (radical cystectomy + total penectomy + bilateral inguinal lymphadenectomy) was proposed to patients with ≥T2 tumors or cN+ with a good performance status, proximal tumor and without severe comorbidities. In case of nodal involvement, neoadjuvant chemotherapy was additionally offered. Patients with localized disease (

CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.

Cyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with known oncogenes, it promotes earlier tumor onset and metastasis. Integrative transcriptomic, metabolomic and functional data reveal that hyperactivation of the serine-glycine-one-carbon network is a metabolic hallmark inherent to CDK12-induced tumorigenesis. Consistently, in retrospective patient cohort studies and in patient-derived xenografts, CDK12-overexpressing breast tumors show positive response to methotrexate-based chemotherapy targeting CDK12-induced metabolic alterations, while being intrinsically refractory to other types of chemotherapy. In a retrospective analysis of hormone receptor-negative and lymph node-positive breast cancer patients randomized in an adjuvant phase III trial to 1-year low-dose metronomic methotrexate-based chemotherapy or no maintenance chemotherapy, a high CDK12 status predicts a dramatic reduction in distant metastasis rate in the chemotherapy-treated vs. not-treated arm. Thus, by coupling tumor progression with metabolic reprogramming, CDK12 creates an actionable vulnerability for breast cancer therapy and might represent a suitable companion biomarker for targeted antimetabolite therapies in human breast cancers.

Aurora B expression as a prognostic indicator and possible therapeutic target in oral squamous cell carcinoma.

The aim of this study is to investigate the expression of the chromosomal passenger protein Aurora B and its activated (phosphorylated) form in a large series of human oral squamous cell cancers (OSCC) and to evaluate its clinical and prognostic significance. Western blotting analysis revealed overexpression of both Aurora B and Thr-232 Phopsho-Aurora B in OSCC lines as compared to normal keratinocytes and bladder cancer cells. Furthermore, protein expression was analysed by immunohistochemistry in 101 OSCC of different site, stage and histological grade and in normal peritumoural areas. The intracellular localization of Aurora B in tumour cells was mainly nuclear, especially in proliferative areas, and significant overexpression was found in tumours in comparison to normal peritumoural areas (P=0.012). Staining results were correlated with clinicopathological parameters and long-term follow-up, and a significant association was found between protein expression and tumour stage (stage II, III and IV vs stage I, P=0.030) and size (<2cm vs >2cm, P=0.010). Cox regression analysis confirmed a poorer disease-free survival in cases with high expression of Aurora B protein. Kaplan-Meier curves showed shorter time to progression in patients with high levels of Aurora B expression (p<0.05). Moreover, the tumoral group with nuclear Aurora B immunolocalization had the worst prognosis (P=0.0364 in disease free survival). Our results suggest that assessing Aurora B expression might help in patients’ risk stratification and serve as a novel therapeutic target in advanced OSCCs.

Primary urethral carcinoma: Results from a single center experience. / Carcinoma uretral primario: resultados de la experiencia de un único centro.

INTRODUCTION AND AIM OF THE STUDY: Primary urethral carcinoma (PUC) is a rare neoplastic disease arising in the urethra, without any evidence of a previous or synchronous carcinoma of the entire urinary tract. Since rare diseases are often incorrectly diagnosed and managed, the aim of this study was to analyze the experience of a single urology center in the treatment of PUC, focusing on neoplasms arising from the male anterior urethra. MATERIALS AND METHODS: Medical records of patients with neoplasms at the level of the penile and bulbar urethra who presented at our tertiary referral center between January 1988 and December 2018 were retrospectively reviewed. Patients with carcinoma of the prostatic urethra were excluded. The diagnosis was obtained with the aid of urethroscopy and lesion biopsy. Local staging was performed by means of contrast-enhanced MRI in selected patients. Staging was achieved by clinical examination, ultrasonography, and CT scan. Radical surgery (radical cystectomy + total penectomy + bilateral inguinal lymphadenectomy) was proposed to patients with ≥T2 tumors or cN + with a good performance status, proximal tumor and without severe comorbidities. In case of nodal involvement, neoadjuvant chemotherapy was additionally offered. Patients with localized disease (

Whole and hemi-gland cryoablation for primary localized prostate cancer: Short and medium-term oncological and functional outcomes. / Crioablación total o hemiglandular para el cáncer de próstata primario localizado: resultados oncológicos y funcionales a corto y medio plazo.

INTRODUCTION: To compare oncological, functional and post-operative outcomes of hemi (HC) vs. whole gland (WGC) cryoablation as first line treatment of localized prostate cancer. MATERIAL AND METHOD: Sixty-six consecutive patients undertaking whole-gland cryoablation (WGC=40) or hemi-cryoablation (HC=26) in a tertiary referral centre between 2010 and 2018 were included. All patients had a low-intermediate risk prostate cancer according to D'Amico risk classification. Hemi-ablation was proposed in case of biopsy and prostate MRI proven unilateral prostate cancer. Primary endpoint was Cryotherapy Failure for which 3 definitions were considered and compared: 1) biochemical failure (> PSA nadir+≥ 2 ng/mL), 2) positive prostate re-biopsy with Gleason score ≥ 7, 3) initiation of further prostate cancer treatment. RESULTS: Median patients age at treatment was 74 [42-81] vs. 76 [71-80] years in WGC vs. HC group, respectively (p=.08). Low and intermediate D'Amico risk group were 15% and 85% vs. 23% and 77% (p=.75), respectively. Median follow- up time was 41 [1.5-99.0] vs. 27 [0.9-93] months (p=.03). Four-years cryotherapy failure free survival in WGC vs. HC were 69% vs. 53% with definition 1 (p=.24), 82% vs. 80% with definition 2 (p=.95), 83% vs. 77% with definition 3 (p=.73). Early and 1-year urinary continence were 60% and 83% in WGC vs. 72% and 83% in HC (p=.26). De novo impotency after cryotherapy was 75% vs. 46% (p=.33) in WGC vs. HC. CONCLUSIONS: In our cohort of highly selected patients with unilateral low/intermediate risk PCa, hemi-cryoablation may provide similar oncological outcomes and less early complications compared to whole-gland cryoablation.

Aberrant DNA hypermethylation of hMLH-1 and CDKN2A/p16 genes in benign, premalignant and malignant endometrial lesions.

PURPOSE OF INVESTIGATION: aberrant gene function and transcriptional silencing by CpG island hypermethylation have become a critical component in the initiation and progression of endometrial cancer. The aim of this study was to investigate the methylation status of genes associated with aberrant DNA hypermethylation in benign, premalignant and malignant endometrial lesions. METHODS: using nested methylation-specific PCR, we assessed the methylation of the promoter regions of two genes, hMLH1 and CDKN2A/p16, in tissue samples from endometrial polyps (EP), atypical hyperplasia (AH) and endometrial cancer (EC). RESULTS: the promoter region of at least one of the two genes was aberrantly methylated in EP (hMLH1 42%, CDKN2A/p16 16%), AH (hMLH1 16%, CDKN2A/p16 50%), EC (hMLH1 50%, CDKN2A/p16 75%). Interestingly, hypermethylation of both genes was found with significant increased frequence in AH and EC, but not in benign lesions. CONCLUSIONS: our preliminary findings seem to suggest that the association of the two genes hMLH1 and CDKN2A/p16 may allow a differential diagnosis between benign and premalignant/malignant endometrial lesions; this further supports the hypothesis that methylation of such DNA mismatch repair and tumour-suppressor genes may be associated with endometrial carcinogenesis thus representing a valuable target for selective pharmacologic therapy.

The impact of age on intravesical instillation of Bacille Calmette-Guerin treatment in patients with high-grade T1 bladder cancer.

Intravesical instillation of Bacille Calmette-Guèrin (BCG) is the standard adjuvant treatment for high-risk non muscle invasive bladder cancer (NMIBC). Since its mechanism of action is supposed to be linked to the immune system efficiency and senescence could negatively affect this efficiency, BCG efficacy in the elderly has been questioned. This study aimed to assess the impact of age on BCG efficacy and safety in patients with high-grade T1 bladder cancer (BC).Among 123 patients with high-grade T1 BCG scheduled for BCG treatment, 82 were <75 year-old (group A) and 41 were ≥75 year-old (group B). Follow-up: urine cytology and cystoscopy every 3 months for the first 2 years, every 6 months for the third year, and then yearly. Tumor recurrence was defined as pathological evidence of disease at the bladder biopsy; tumor progression was defined as pathological shift to muscle invasive disease at the bladder biopsy or the imaging techniques showing recurrent BC and distant metastasis likely related to it.The median follow-up was 65 months (range 11-152). Recurrence occurred in 35 patients, 19 (23.2%) in the group A and 16 (39%) in the group B. Progression occurred in 18 patients, 12 (14.6%) in the group A and 6 (14.6%) in the group B. Recurrence free rate was similar in both groups up to 2 years. The 5 years progression rate was almost the same in both groups A and B (85.9% vs 84.7%), whereas the 5 years cancer-specific survival (CSS) was 92.6% in the group A and 85.4% in the group B. Of the 18 patients with progression, 11 underwent cystectomy; 12 patients died because of their BC. Kaplan-Meier plots pointed out no difference in recurrence-free, progression-free, and CSS between the 2 groups. Adverse events were similar in the 2 groups. Only 4 (3.3%) patients, 2 (2.4%) in the group A and 2 (4.8%) in the group B, experienced mild adverse reactions compatible with treatment.Elderly patients with high-grade T1 BC are not poorer candidates to BCG treatment, as they had similar benefit and adverse reactions than those aging ≥75 years.

Large oral soft tissue metastasis from anaplastic carcinoma of the lung mimicking a primitive malignancy: case report and brief review of the literature.

Metastatic tumours to the oral region are rare, and those reported in the buccal soft tissues are even less frequent. We describe a case of anaplastic carcinoma of the lung in a 60-year-old man, presenting a huge oral metastasis as the first sign of his primitive lung malignancy. Clinically, the oral lesion mimicked a high-grade primitive carcinoma of the oral cavity. The biopsy established the gingival metastasis from lung cancer which was confirmed by a fine-needle aspiration cytology examination. We report an uncommon case of metastatic lung carcinoma to the gingiva emphasizing the differential diagnosis between primary and metastatic tumours; a short discussion on the pathways of metastatization to oral cavity soft tissues, as well as brief review of the literature are also presented.

Fragmentation targeted at preferred discontinuities: A new concept in endolithotripsy with Holmium laser:YAG. / Fragmentación dirigida a discontinuidades preferentes: un nuevo concepto en endolitotricia con láser Holmium:YAG.

INTRODUCTION: There are currently 3holmium laser, YAG (Ho:YAG) endolithotripsy procedures that are considered basic (fragmentation, pulverisation, "pop-corn" technique). We present the technique of fragmentation targeted at preferred discontinuities (FTPD), a new concept of endolithotripsy by Ho:YAG laser. MATERIAL AND METHODS: The FTPD technique is based on the selective application of energy (targeting a specific preselected point) to an area that is visually prone to the formation of a fracture line or preferred discontinuity (conditioned by the anisotropy of the urolithiasis). The ideal energy regimen (setting) is a high range of working energy (2-3J) with a very low frequency range (5-8Hz) and short pulse width. Between January 2015 to February 2017, the FTPD technique was used in 37 procedures (7 NLP, 16 RIRS, 12 URS, 2 cystolithotomies), with a Ho:YAG laser (Lumenis Pulse 120H®, Tel-Aviv, Israel). Maximum power used: 24W (3J/8Hz) with fibres of 365µ and 273µ (URS, RIRS), and 32W (4J/8Hz) with fibres of 550µ (NLP, cystolithotomy). RESULTS: Strategic improvement was achieved in all cases using the TFPD technique to continue the endolithotripsy or remove fragments. No complications were recorded after the use of this method. CONCLUSIONS: FTPD can be considered a complementary option in combination with the basic methods of fragmentation and pulverisation. In our experience, it constitutes significant progress in optimising the performance of Ho:YAG laser endolithotripsy.

Cyclooxygenase isozymes in oral squamous cell carcinoma:a real-time RT-PCR study with clinic pathological correlations.

COX-2 expression in tumour cells has been associated with carcinogenesis in many human neoplasms, including head and neck cancer, while the COX-1 isoform of the cyclooxygenase enzyme is constitutively expressed in normal tissues. We measured COX-1 and COX-2 m-RNA expression in samples of both oral cancer and matched oral mucosa from 22 patients by RealTime RT-PCR; clinic pathological data (grading, TNM staging, inflammation, follow-up) of all patients were available for statistical evaluation. Most of the tumor samples in our study expressed at least one cyclooxygenase enzyme (COX-1 or COX-2 mRNA) more than their matched normal oral mucosa (p<0.05), with no correlation with the entity of inflammation, and a significant inverse relationship was found between COX-1 and COX-2 in each sample. Higher levels of COX-2 expression were associated with poor disease-free survival (p<0.05), but not with overall survival and higher tumor stage and grade. Our results suggest that COX-1 may play a role in oral carcinogenesis, and could be regarded as a potential therapeutic target by chemo preventive drugs; moreover, COX-2 expression might be addressed as a new prognostic tool in the clinical management of OSCC.

Confocal laser scanning microscope study of terminal villi vessels in normal term and pre-eclamptic placentas.

The aim of this study was to compare immunocytochemical confocal scanning laser microscopy measures of villus capillarization in control placentas with pre-eclamptic ones. Accordingly, placentas from normal term pregnancies (n=3) and cases of late-onset pre-eclampsia without intrauterine growth retardation (IUGR) featuring normal uterine artery Doppler (n=3) were analyzed by confocal scanning laser microscopy (CSLM), which is a powerful technique for obtaining three-dimensional reconstructions of any kind of blood vessels (arteries, veins, capillaries). A laser light beam is used in order to detect CD34 antibody-related immunofluorescence, which is a marker of endothelial cells. Villus capillarization was assessed by estimating the following parameters: number of pixels, mean, maximum and minimum immunofluorescence amplitude. Our results show a significant hyper-ramification of the capillary loop in pre-eclamptic placentas, featuring irregular profile and narrow lumina. Such findings support the hypothesis that several agents causing angiogenesis and vasoconstriction affect villus vessels in pre-eclamptic placentas, thus promoting a lasting condition of fetal hypoxia by decreasing endothelial surface and materno-fetal exchanges.

Role of Runx2 phosphorylation in prostate cancer and association with metastatic disease.

The osteogenic transcription factor, Runx2, is abnormally expressed in prostate cancer (PCa) and associated with metastatic disease. During bone development, Runx2 is activated by signals known to be hyperactive in PCa including the RAS/MAP kinase pathway, which phosphorylates Runx2 on multiple serine residues including S301 and S319 (equivalent to S294 and S312 in human Runx2). This study examines the role of these phosphorylation sites in PCa. Runx2 was preferentially expressed in more invasive PCa cell lines (PC3>C4-2B>LNCaP). Furthermore, analysis using a P-S319-Runx2-specific antibody revealed that the ratio of P-S319-Runx2/total Runx2 as well as P-ERK/total ERK was highest in PC3 followed by C4-2B and LNCaP cells. These results were confirmed by immunofluorescence confocal microscopy, which showed a higher percentage of PC3 cells staining positive for P-S319-Runx2 relative to C4-2B and LNCaP cells. Phosphorylated Runx2 had an exclusively nuclear localization. When expressed in prostate cell lines, wild-type Runx2 increased metastasis-associated gene expression, in vitro migratory and invasive activity as well as in vivo growth of tumor cell xenografts. In contrast, S301A/S319A phosphorylation site mutations greatly attenuated these Runx2 responses. Analysis of tissue microarrays from 129 patients revealed strong nuclear staining with the P-S319-Runx2 antibody in primary PCas and metastases. P-S319-Runx2 staining was positively correlated with Gleason score and occurrence of lymph node metastases while little or no Runx2 phosphorylation was seen in normal prostate, benign prostate hyperplasia or prostatitis indicating that Runx2 S319 phosphorylation is closely associated with PCa induction and progression towards an aggressive phenotype. These studies establish the importance of Runx2 phosphorylation in prostate tumor growth and highlight its value as a potential diagnostic marker and therapeutic target.

Failure of detection of the tyrosine to histidine substitution at the residue 33 of thymidylate synthase in human colorectal cancer. A preliminary study.

Structural changes in the macromolecular targets of pharmacological agents can result in alterations in the efficacy of these agents. In previous studies Berger et al. (1) identified a variant structural form of thymidylate synthase (TS) that is associated with relative resistance to 5-fluoro-2'-deoxyuridine, in a human colonic tumor cell line. They observed that expression of the variant TS, which differs from the normal form by a tyrosine to histidine substitution at residue 33, confers a 4-fold level of drug resistance in mammalian cells, as well as in bacteria. Now we report on the use of RT-PCR techniques to see if that variant TS form could be present in human samples from patients who underwent surgery for primary colorectal cancer and been previously untreated and to try to find relationships between that hypothetical variant TS form and the 5-Fluorouracil treatment. The possible role of Tyr-33 in 5-fluoropyrimidine-mediated inhibition of TS is discussed.

The role of thymidylate synthase levels in the prognosis and the treatment of patients with colorectal cancer.

Inhibition of Thymidylate Synthase (TS) by the 5-Fluorouracil (5Fu) active metabolite Fluoro-deoxy-uridine-monophosphate (FdUMP) is considered to be the main mechanism of action of 5Fu. TS level from tumors and normal mucosa of 62 untreated patients who underwent surgery for primary colorectal adenocarcinoma was performed. The aim of this study was to evaluate the possibility of considering the TS level as a prognostic factor of the disease. A large variation in the level of the enzyme was found among tumors. Our data demonstrate that there is no association with age, sex, and tumor size; however there are significant relationships between TS levels and staging and histological grading. In fact the TS values are higher in Dukes' A and in G1 than in Dukes' D and G3 tumors (p < 0.05). Another significant association has been found between the TS level and tumor site: pts with right colon neoplasias had higher TS levels than pts with left and rectum ones. An interesting trend was found between the TS levels and survival parameters. Pts who had lower TS levels had a significantly increased risk of death (p < 0.05) over pts with a higher outcome. Our data support the hypothesis that a high TS level is a favourable prognostic factor in human untreated colorectal carcinomas according to our previous preliminary data (1).

[Sarcoidosis presenting with Raynaud's syndrome: a case report]. / Fenomeno di Raynaud come esordio di sarcoidosi: descrizione di un caso clinico.

We report a case of association between sarcoidosis and Raynaud's syndrome. A 39 year old female presented fatigue, Raynaud's syndrome, IgG and erithrosedimentation rate (ESR) increase, polyarthralgy in which disseminated micronodular infiltration in the chest X-ray and histological demonstration of non-caseating epitheloid microgranulomas led to a diagnosis of concomitant sarcoidosis. Clues to the diagnosis of sarcoidosis coexisting with autoimmune disease are discussed.