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3.
Br J Cancer ; 112(12): 1921-8, 2015 Jun 09.
Article in English | MEDLINE | ID: mdl-25942399

ABSTRACT

BACKGROUND: Despite major advances in the management of metastatic colorectal cancer (mCRC) with liver-only involvement, relapse rates are high and reliable prognostic markers are needed. METHODS: To assess the prognostic impact of BRAF and RAS mutations in a large series of liver-resected patients, medical records of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially curative liver resection were selected. BRAF and RAS mutational status was tested on primary and/or metastases by means of pyrosequencing and mass spectrometry genotyping assay. Primary endpoint was relapse-free survival (RFS). RESULTS: In the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt) patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7, 11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043). At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09-4.87; P=0.029) and to RAS mutant (multivariate HR=2.06; 95% CI, 1.02-4.14; P=0.044). Similar results were obtained in terms of overall survival. Compared with all wt patients, RAS mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05-2.07; P=0.025), but such effect was lost at multivariate analyses. CONCLUSIONS: BRAF mutation is associated with an extremely poor median RFS after liver resection and with higher probability of relapse and death. Knowledge of BRAF mutational status may optimise clinical decision making in mCRC patients potentially candidate to hepatic surgery. RAS status as useful marker in this setting might require further studies.


Subject(s)
Colorectal Neoplasms/genetics , Genes, ras , Liver Neoplasms/genetics , Liver Neoplasms/surgery , Mutation , Proto-Oncogene Proteins B-raf/genetics , Aged , Biomarkers, Tumor/genetics , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/pathology , Disease-Free Survival , Female , Humans , Liver Neoplasms/enzymology , Liver Neoplasms/secondary , Male , Middle Aged , Prognosis , ras Proteins/genetics
4.
Acta Gastroenterol Belg ; 73(2): 287-91, 2010.
Article in English | MEDLINE | ID: mdl-20690573

ABSTRACT

Amyloidosis, a potentially fatal disease, is characterized by an abnormal deposition of autologous proteins. Heart, liver, kidneys, lung, thyroid, skin and the gastrointestinal tract can be involved; in this last case mucosal alterations or disturbances of the motility leading to pseudo-obstruction, bleeding, diarrhea and malabsorption can be present. However, the data concerning the possible gastrointestinal presentations of amyloidosis are scanty and heterogeneous. We report the case of a patient presenting severe gastrointestinal symptoms caused by a megaduodenum. The patient was thoroughly investigated and lesions appeared limited to the upper gastrointestinal tract in the absence of a systemic disorder. However, at follow up the patient developed cardiac dilatation and bioptic samples revealed the presence of amyloidosis.


Subject(s)
Amyloidosis/diagnosis , Duodenal Diseases/etiology , Amyloidosis/complications , Amyloidosis/pathology , Dilatation, Pathologic , Duodenal Diseases/pathology , Fatal Outcome , Humans , Male , Middle Aged , Myocardium/pathology
5.
Ann Oncol ; 20(2): 265-71, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18765464

ABSTRACT

BACKGROUND AND AIM: Capecitabine is an orally bioavailable prodrug that is converted to 5-fluorouracil through several enzymatic steps, the last of which is mediated by thymidine phosphorylase (TP). TP has been reported to be expressed at higher levels in cancer tissue compared with normal counterpart. The present study aimed at evaluating the potential relationship between TP expression and benefit from capecitabine in patients with metastatic breast cancer (BC). METHODS: Immunohistochemistry for TP and other biological markers was carried out on paraffin-embedded cancer tissues of 61 patients with BC treated with at least three cycles of capecitabine as single agent for metastatic disease. All patients had received capecitabine 1000 mg/m(2) b.i.d. days 1-14 every 21 days. The following variables were analyzed as potential determinants of benefit from capecitabine: TP expression, estrogen receptor (ER) and progesterone receptor status, human epidermal growth factor receptor-2 (HER-2) status, MIB-1 expression, performance status at the beginning of capecitabine treatment, stage at diagnosis, grade, presence of visceral metastases at the beginning of capecitabine treatment, and previous chemotherapy. RESULTS: Overall, median time to progression (TTP) was 6.5 months (range 1.4-33). On multivariate analysis, ER status [hazard ratio (HR) for progression = 0.31; 95% confidence interval (CI) = 0.15-0.64; P = 0.002], presence of visceral metastases at the beginning of capecitabine treatment (HR = 2.30; 95% CI = 1.21-4.39; P = 0.01), and capecitabine as first- or second-line treatment (HR = 2.28; 95% CI = 1.21-4.32; P = 0.01) independently predicted TTP. TP was highly expressed in 34 of 61 cases (55.7%). In the subgroup of patients with TP-expressing tumor, TTP was significantly longer in patients who received anthracyclines and taxanes before capecitabine (median TTP 7.5 versus 3.3 months, P = 0.01, log-rank test). Similarly, patients with a TP-positive tumor showed a longer TTP if they received taxanes before capecitabine than patients with TP-positive tumor who did not receive this treatment (7.3 versus 3.4 months, P = 0.03). CONCLUSIONS: These data provide further evidence that TP expression in BC could represent a biomarker of sensitivity to capecitabine treatment. Prospective studies with translational approach are desirable to confirm the predictive and prognostic role of TP.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/enzymology , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Thymidine Phosphorylase/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Capecitabine , Deoxycytidine/therapeutic use , Disease Progression , ErbB Receptors/metabolism , Female , Fluorouracil/therapeutic use , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Thymidine Phosphorylase/analysis , Time Factors , Treatment Outcome , Ubiquitin-Protein Ligases/metabolism
6.
G Ital Nefrol ; 25(4): 459-74, 2008.
Article in Italian | MEDLINE | ID: mdl-18663693

ABSTRACT

Hematopoietic stem cell transplantation, autologous or allogeneic, is a well established hematology procedure. There can be a number of renal complications in this setting, which may occur in every phase but all strongly influence prognosis. Among the late complications, there is the well-known possibility of progressive chronic renal failure, appearing together with hypertension and modest alterations of the urinary sediment, and characterized by pathological findings of thrombotic microangiopathy, often without the corresponding clinical aspects. This clinical picture must be distinguished from other forms of clinically more severe thrombotic microangiopathy, such as those occurring in the early post-transplant period, and from other causes of renal disease in the hematopoietic stem cell transplantation setting. Total body irradiation, chemotherapeutic drugs, calcineurin inhibitors and opportunistic infections have all been considered as causal factors. The nosological classification is still poorly defined, as are the real prognosis and the best treatment. Kidney biopsy is a necessary tool to make a correct diagnosis, assess the frequency of the condition, make a prognostic judgment, and set up rational treatment.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Kidney Failure, Chronic/etiology , Female , Humans , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/therapy , Middle Aged , Prognosis
7.
J Neurooncol ; 78(3): 317-20, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16598427

ABSTRACT

A rare embryonal brain tumor has been diagnosed in a 4-year-old boy. The mass, located at the pons and mesencephalon, has been histologically classified as an embryonal tumor containing abundant neuropil and true rosettes. After surgical complete removal of the neoplasia, the child received intensive combined chemotherapy and radiotherapy. He is alive and free of disease at 34 months from surgery. Difficulties in histological definition, possible suggestions for treatment proposals are discussed.


Subject(s)
Brain Neoplasms/pathology , Neuroectodermal Tumors, Primitive/pathology , Neuropil/pathology , Brain Neoplasms/classification , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Child, Preschool , Combined Modality Therapy , Humans , Magnetic Resonance Imaging , Male , Mesencephalon/pathology , Neuroectodermal Tumors, Primitive/classification , Neuroectodermal Tumors, Primitive/drug therapy , Neuroectodermal Tumors, Primitive/radiotherapy , Pons/pathology , Treatment Outcome
8.
Clin Nephrol ; 61(5): 352-6, 2004 May.
Article in English | MEDLINE | ID: mdl-15182131

ABSTRACT

Castleman's is an uncommon lymphoproliferative disorder secondary to lymphoid follicle hyperplasia and marked capillary proliferation with endothelial hyperplasia. This illness can be associated with glomerulonephritis (GN). Here, we report a case with steroid-dependent nephrotic syndrome secondary to proliferative mesangial glomerulonephritis in a patient with Castleman's disease, that was diagnosed several years before. Considering the involvement of IL-6 in Castleman's disease we treated the patient with thalidomide obtaining the remission of the nephrotic syndrome. Our experience suggests a possible role of thalidomide in the treatment of glomerular pathology when a role of IL-6 is hypothesized.


Subject(s)
Castleman Disease/complications , Glomerulonephritis, Membranoproliferative/complications , Immunosuppressive Agents/therapeutic use , Nephrotic Syndrome/drug therapy , Thalidomide/therapeutic use , Aged , Biopsy , Female , Glomerulonephritis, Membranoproliferative/drug therapy , Glomerulonephritis, Membranoproliferative/pathology , Humans , Kidney Glomerulus/pathology , Nephrotic Syndrome/etiology
9.
Ultrastruct Pathol ; 28(4): 181-97, 2004.
Article in English | MEDLINE | ID: mdl-15693630

ABSTRACT

Electron microscopy defined classic patterns of hereditary glomerular disease long before genetics revealed an underlying specific mutation. Genetic analysis is now easier to perform in clinical practice but an earlier optimism that genetics would predict disease severity and phenotype is challenged. The classic paradigm is Alport nephritis in which only a subset of mutations may predict glomerular abnormalities and disease severity. Interpretation of ultrastructural pathology of monogenetic diseases like Alport nephritis is complicated when the proband is the first family member to be diagnosed or there is discrepancy between clinical presentation and ultrastructural changes. In this review the authors have selected a dozen cases representative of common monogenetic glomerular diseases as a platform to discuss the utility of diagnostic electron microscopy in the era of molecular genetics. The emphasis is on genotype/glomerular phenotype correlations.


Subject(s)
Kidney Diseases/genetics , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Kidney Glomerulus/ultrastructure , Microscopy, Electron, Transmission , Adolescent , Adult , Aged , Child, Preschool , Female , Genotype , Humans , Infant , Kidney Glomerulus/physiology , Male , Phenotype
10.
G Ital Nefrol ; 21 Suppl 26: S19-27, 2004.
Article in Italian | MEDLINE | ID: mdl-15732040

ABSTRACT

Although the diagnostic and therapeutic outcome of renal transplantation has successfully improved during the last decades, acute graft rejection (AGR) is still an ongoing cause of concern being often associated with irreversible graft dysfunction. Renal biopsy remains a valuable tool in the initial assessment of the potential graft malfunction especially during the early post-transplant period. It is an accurate and sensitive means for detecting prognostically relevant microscopic abnormalities, and assisting in subsequent patient management. For long time, the histopathologic evaluation of AGR has suffered from an irreducible bias with poor interobserver rates. Nowadays, the classification schemes of AGR include the BANFF approach and the National Institute of Heath Collaborative Clinical Trials in Transplantation (NIH-CCTT) system: both have been originally designed in order to improve the diagnostic reproducibility of AGR among pathologists. Arteritis and tubulitis, along to clinical information, constitute the cardinal features of the BANFF classification. Distinguishing features of the traditional NIH-CCTT system includes microscopic criteria such as assessment of interstitial hemorrhage, extent and quality of inflammatory infiltrate, and acute glomerulitis, in addition to tubulitis and arteritis. The BANFF classification has apparently gained more popularity than the time-honored NIH-CCTT system since, if used in the appropriate clinical context, it allows a more accurate assessment of AGR, provides prognostically relevant information, and has a better reproducibility rate among pathologists. Nevertheless, the accuracy trend has not significantly improved during the last few years.


Subject(s)
Graft Rejection/diagnosis , Kidney Transplantation , Kidney/pathology , Acute Disease , Arteritis/diagnosis , Graft Rejection/classification , Graft Rejection/pathology , Humans , Inflammation/diagnosis , Kidney/blood supply , Kidney/surgery , Kidney Transplantation/pathology , Kidney Tubules/pathology , Observer Variation , Reproducibility of Results
11.
Cancer ; 85(9): 1910-6, 1999 May 01.
Article in English | MEDLINE | ID: mdl-10223229

ABSTRACT

BACKGROUND: Extragonadal yolk sac tumors of the gastrointestinal tract are extremely rare neoplasms. Their greater rarity compared with other extragonadal yolk sac tumors suggests that different pathogenetic mechanisms could be involved according to the site of origin. This report describes a case of a combined yolk sac tumor and adenocarcinoma that arose in a gastric stump in a man age 61 years 43 years after he underwent distal gastric resection and gastrojejunostomy (Billroth II operation) for a benign duodenal ulcer. The coexistence of an adenocarcinomatous component with the yolk sac component suggests that the two histologic patterns may represent distinct phenotypes arising from a common mucosal epithelial cell. METHODS: Immunohistochemical and molecular techniques were used to define the mutation pattern of p53 in both components of the tumor. RESULTS: Single-strand conformation polymorphism and sequencing analyses demonstrated the same pattern of p53 mutation in the adenocarcinomatous and yolk sac tumor components. CONCLUSIONS: This finding suggests that the two tumors could have been derived from the same cellular clone and supports the hypothesis that the two components represented a heterogeneous differentiation of the same tumor.


Subject(s)
Adenocarcinoma/genetics , Endodermal Sinus Tumor/genetics , Gastric Stump/pathology , Neoplasms, Multiple Primary/genetics , Stomach Neoplasms/genetics , Adenocarcinoma/pathology , Clone Cells , DNA, Neoplasm/genetics , Endodermal Sinus Tumor/pathology , Genes, p53 , Humans , Immunohistochemistry , Male , Middle Aged , Mutation , Neoplasms, Multiple Primary/pathology , Stomach Neoplasms/pathology , Stomach Ulcer/surgery
12.
Adv Clin Path ; 3(1-2): 35-41, 1999.
Article in English | MEDLINE | ID: mdl-10655572

ABSTRACT

Thymic carcinomas (primitive malignant epithelial neoplasms of the thymus) are rare tumors which generally remain silent for long periods and rarely metastatize outside the chest. The authors present a case of a 49 year-old patient, with mediastinal mass complicated by pericardial effusion and rapidly extensive liver metastasis. Data in the literature indicate that completeness of the excision at initial operation is the most important prognostic factor, but the presence of necrosis, high number of mitosis and endolymphatic emboli in the specimens could indicate a poor prognosis, suggesting a tempestive treatment and a close follow-up.


Subject(s)
Liver Neoplasms/secondary , Thymoma/secondary , Thymus Neoplasms/pathology , Diagnosis, Differential , Humans , Liver Neoplasms/diagnostic imaging , Male , Mediastinal Neoplasms/diagnostic imaging , Mediastinal Neoplasms/secondary , Middle Aged , Radiography, Thoracic , Thymoma/diagnostic imaging , Thymus Neoplasms/diagnostic imaging , Tomography, X-Ray Computed
14.
Anal Quant Cytol Histol ; 18(6): 438-52, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8978868

ABSTRACT

OBJECTIVE: To correlate stage-related and histologic features of non-small cell lung cancer (NSCLC) with DNA flow cytometric parameters. STUDY DESIGN: The clinicopathologic features, DNA flow cytometric parameters (ploidy type, S-phase fraction and DNA index [DI]) of 72 surgically resected NSCLC were reviewed. RESULTS: NSCLC were classified on the basis of their DI in diploid, peridiploid, hypotriploid, triploid, hypertriploid, tetraploid, hypertetraploid and multiploid tumors. DI was significantly related to pleural infiltration, pT, histologic type and evidence of necrosis. Tumors infiltrating the pleura were mostly triploid or hypertriploid; high pT stages were also hypertetraploid. Adenocarcinomas showed a wide DI distribution, squamous carcinomas were mostly diploid, triploid or hypertriploid and large cell carcinomas were mostly triploid, hypertriploid and hypertetraploid. The best combination of features able to predict disease relapse was pT plus pN plus grading and divergent differentiation. CONCLUSION: Many stage-related and histologic features are associated with particular DI classes, which vary in relation to the feature itself and, in some cases, regardless of classical methods of grading and histologic typing. DNA content analysis highlights greater biologic heterogeneity in NSCLC than evidenced morphologically.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , DNA, Neoplasm/analysis , Flow Cytometry/methods , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Adult , Age Factors , Aged , Female , Humans , Male , Middle Aged
15.
Anal Quant Cytol Histol ; 18(5): 355-60, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8908307

ABSTRACT

OBJECTIVE: To evaluate and correlate morphologic features, glial fibrillary acidic protein (GFAP) reactivity and DNA content parameters in 32 pleomorphic adenomas of the salivary glands. STUDY DESIGN: The adenomas were subclassified according to the proportion of stroma and type of stromal differentiation. DNA flow cytometry was carried out on paraffin-embedded material. GFAP reactivity was determined immunohistochemically and evaluated as the percentage of positive cells. Follow-up ranged from 17 to 71 months; no recurrences were observed. RESULTS: Seven cases were aneuploid, 10 peridiploid and 15 diploid. Nondiploid tumors had a significantly higher S-phase fraction. Nondiploid adenomas were significantly associated with a greater percentage of stroma, while S-phase fraction showed only a trend toward being higher in tumors with a greater quota of stroma. Ploidy type and S-phase fraction were unrelated to sex, age, tumor diameter or site. GFAP reactivity was unrelated to subtype or S-phase fraction; a higher frequency of diploid tumors was seen among cases with a greater number of reactive cells. CONCLUSION: Aneuploidy is present in a significant percentage of typical cases. It is unrelated to tumor bulk and appears to have no effect on recurrence as long as surgical excision is complete.


Subject(s)
Adenoma, Pleomorphic/chemistry , DNA/analysis , Flow Cytometry , Glial Fibrillary Acidic Protein/analysis , Salivary Gland Neoplasms/chemistry , Adenoma, Pleomorphic/classification , Adolescent , Adult , Age Factors , Aged , Female , Humans , Immunohistochemistry , Male , Middle Aged , Ploidies , Retrospective Studies , S Phase , Salivary Gland Neoplasms/classification , Sex Factors
17.
Am J Pathol ; 147(2): 434-44, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7639336

ABSTRACT

Apoptosis seems to be involved in different stages of immune cell development. In particular, experimental evidence suggests that it is a major form of cell death in the thymus. The present analysis of human thymocytes reveals that a fraction of these cells, cultured in vitro, undergoes spontaneous apoptosis. This observation is based both on molecular (DNA fragmentation) and morphological (electron microscopic) investigations of the cells. The apoptotic thymocytes are CD3- or CD3lo, CD4lo, and CD8lo and do not express Bcl-2 protein. Furthermore, thymocytes die by apoptosis when exposed to pharmacological stimuli, such as tumor necrosis factor-alpha, dexamethasone, ATP, or Ca++ ionophore. Thus the apoptotic machinery in thymocytes can be triggered by an imbalance in growth factors in the in vitro culture media and can be modulated by various biochemical signals. The process of spontaneous apoptosis is independent of mRNA or protein synthesis, as actinomycin D and cycloheximide fail to inhibit this phenomenon. Furthermore, apoptosis seems to require active oxidative phosphorylation, as it is prevented by incubation of the cells with inhibitors of the respiratory chain.


Subject(s)
Apoptosis , Thymus Gland/cytology , Child, Preschool , Humans , Infant , Infant, Newborn , Lymphocyte Subsets/physiology , Microscopy, Electron , Oxygen Consumption , Phenotype , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2 , Stimulation, Chemical , Thymus Gland/physiology
18.
Cardiovasc Pathol ; 4(1): 47-55, 1995.
Article in English | MEDLINE | ID: mdl-25850780

ABSTRACT

Right ventricular dysplasia (RVD) is a cardiac anomaly characterized by replacement of variable amounts of right ventricular myocardium by adipose tissue. This condition is believed to be a selective disorder involving extensively the right ventricle, but there are occasional reports of concomitant "minor" abnormalities of the left ventricle. The object of this report concerns a patient who died after heart transplantation because of an unsuspected RVD of the donor heart. We present a morphometric study of the heart in order to evaluate the distribution of the fat on both ventricles and to understand the structural basis of the heart failure. The results show that a large portion of the right ventricle is replaced by fat with a quite homogeneous distribution; the left ventricle is also largely replaced by adipose tissue that is primarily localized at the apex and decreases from the apex to the basis. The remodeling of the heart is attributable to a conspicuous increase in volume of the right ventricle associated with a normal number of myocytes that are longer than normal. For these reasons, according to Starling's law, the heart develops congestive failure.

19.
Cancer ; 73(5): 1332-4, 1994 Mar 01.
Article in English | MEDLINE | ID: mdl-8111697

ABSTRACT

The occurrence of an accessory liver is extremely rare and usually has no clinical significance. This malformation may harbor the same pathologic processes present in the anatomically normal liver.


Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Liver/abnormalities , Carcinoma, Hepatocellular/complications , Humans , Liver Neoplasms/complications , Male , Middle Aged
20.
Nephron ; 67(1): 104-8, 1994.
Article in English | MEDLINE | ID: mdl-8052350

ABSTRACT

We describe a case, seemingly sporadic, in which ocular and acral malformations were associated with an interstitial nephropathy; we made a diagnosis of acro-renal-ocular syndrome. There was no stasis, reflux, or urinary tract infection in our patient. We believe that interstitial nephritis in acro-renal-ocular syndrome may not always be pyelonephritis, as previously reported.


Subject(s)
Bone and Bones/abnormalities , Eye Abnormalities/complications , Nephritis, Interstitial/complications , Pyelonephritis/complications , Adult , Diagnosis, Differential , Extremities , Female , Humans , Nephritis, Interstitial/diagnosis , Nephritis, Interstitial/pathology , Pyelonephritis/diagnosis , Pyelonephritis/pathology , Syndrome , Uterus/abnormalities
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