Value of real-time gastric juice analysis in upper gastrointestinal endoscopy.

AIM: Esophagogastroduodenoscopy (EGDS) cannot identify microscopic lesions. We determined the contribution of real-time gastric juice analysis in detecting lesions non-detectable with the simple endoscopic inspection. METHODS: Endoscopy, histology and gastric juice analysis were performed in 216 patients. We assessed six diagnostic strategies: EGDS (strategy-1), EGDS with antral biopsies (hematoxylin-eosin staining) in hypochlorhydrics (strategy-2) or all patients (strategy-3), EGDS with antral and fundic biopsies (hematoxylin-eosin staining) in hypochlorhydrics (strategy-4) or all patients (strategy-5), EGDS with antral and fundic biopsies (hematoxylin-eosin + immunohistochemical staining) in hypochlorhydrics (strategy-6). Then, we determined how many of the pathological conditions identified by the complete histological evaluation would have been detected by each strategy. RESULTS: In total, 220 pathological conditions were identified. Hypochlorhydria was correlated (r=0.67; P<0.01) with histological lesions (85% lesions were detected in hypochlorhydrics) and high ammonium levels, with H.pylori infection (r=0.69; P<0.01). Strategy-1 identified only 5% conditions, while strategies 3 and 5 detected 68.6% and 83.2% conditions, respectively. Strategies 2, 4 and 6 (based on gastric juice analysis) yielded detection rates (61.4%, 75.5%, 90.9%) similar to or better than those of strategies 3 and 5. CONCLUSION: Real-time gastric juice analysis provided information about the presence of gastric lesions in an otherwise "normal" stomach at EGDS. It improved the diagnostic yield and optimized resource utilization without any additional effort by the endoscopist.

Perendoscopic real-time assessment of pH improves detection of gastric preneoplastic conditions.

AIM: Gastric juice may constitute a precious source of clinicopathological information. We assessed the usefulness of real-time, perendoscopic, gastric juice pH determination in identifying preneoplastic conditions of the stomach, that often escape the mere endoscopic evaluation. METHODS: The study included 245 patients (115M; 130F; age 47±17). In each of them perendoscopic gastric juice pH was assessed by means of an innovative device, the Endofaster, and the results were correlated with histological evaluation (H&E, immunohistochemistry, argyrophil stains), and gastric acid secretion (BAO-PAO), and serum gastrin levels. The conditions evaluated were: atrophy, intestinal metaplasia, endocrine cell hyperplasia, hypergastrinemia. RESULTS: A total of 136 pathological conditions were detected and these resulted to be correlated with pH (r=0.67; P<0.01). The rate of pathological conditions was low in normochlorhydric patients (14.1%); most of these conditions were concentrated in patients with hypochlorhydria (85.9%) (P<0.001). Specifically, the number of patients with one or more pathological conditions increased proportionately with the rise in pH levels. An inverse correlation was detected between gastric juice pH and basal acid output (BAO) (r=-0.72; P<0.01). Endoscopic feature was normal/mild in most of patients with pathological conditions. CONCLUSION: Hypochlorhydria is a sensitive indicator of gastric risk conditions. Perendoscopic real-time assessment of pH can improve and extend optical analysis by allowing the detection of pathological conditions (either preneoplastic or not) that often escape diagnosis because not correlated with specific endoscopic pattern.

Successful treatment of Schnitzler's syndrome with anakinra after failure of rituximab trial.

We report a 50-year-old man who presented with a 5-year history of an intermittent widespread pruritic urticarioid rash and fever, fatigue, arthralgia and a monoclonal immunoglobulin-M paraprotein. The patient was initially treated with antihistamines and corticosteroids without the disappearance of symptoms. A skin biopsy from the urticarial rash on the thorax was performed, revealing dermal mononuclear and polymorphonuclear cell infiltrate and normal epidermis. A diagnosis of Schnitzler's syndrome (SS), a rare disorder in which the simultaneous occurrence of monoclonal gammopathy and chronic urticaria is usually observed, was made. After an unsuccessful trial with rituximab at a dosage of 375 mg/sqm weekly for 4 consecutive weeks, the patient was treated with anakinra, an inhibitor of interleukin-1alpha that is thought to be involved in the pathogenesis of the disease, at a dose of 100 mg daily given subcutaneously. He showed a prompt response to the drug and he is still well and symptom-free after 12 months of follow-up. On the basis of both this experience and the review of the literature we conclude that anakinra may be a promising option for the treatment of SS. However, these results need to be confirmed on a larger number of patients.

Pleomorphic hyalinizing angiectatic tumor of the male breast: a heretofore unreported occurrence.

Pleomorphic hyalinizing angiectatic tumor (PHAT) is considered an unusual mesenchymal tumor of intermediate malignant potential that is distinguished by a prominent angiectatic vasculature with clusters of thin-walled, fibrin-lined vessels surrounded by sheets of spindled and pleomorphic cells. This lesion occurs mostly in the subcutaneous soft tissues of the lower extremities. In this paper, the authors report the first case of PHAT involving the breast parenchyma of a 75-year-old man. The patient was referred to the hospital with a history of a painless left breast mass that had been growing for several years. The lesion did not recur after surgery. The tumor exhibited histopathologic and immunohistochemical features identical to those of a PHAT of other sites. The purpose of this report is to add a rare tumor to the differential diagnosis of mammary spindle cell neoplasms.

The effect of prebiotics in the management of neonatal hyperbilirubinaemia.

BACKGROUND: Breast milk oligosaccharides such as galacto-oligosaccharides (scGOS) and fructo-oligosaccharides (lcFOS) can influence the intestinal microbial flora. The latter, in turn, can modulate several intestinal and extraintestinal functions, including bilirubin metabolism. Supplementing infant formula with a prebiotic mixture might then be a novel and safe intervention to manage mild neonatal hyperbilirubinaemia. AIM: To investigate the effect of dietary supplementation with prebiotics on moderate hyperbilirubinaemia in healthy, term infants. METHODS: A prospective, double-blind, clinical trial was performed on seventy-six consecutive newborns who were randomly assigned to receive a formula containing 0.8 g/dL of a mixture from scGOS and lcFOS (ratio 9:1), or maltodextrines as placebo for 28 days. Bilirubin levels were determined by the transcutaneous bilirubin measurement within 2 h after birth (T1), at 24, 48 and 72 h and at 5, 7, 10 and 28 days of life. The number of stool per day was also recorded. RESULTS: Neonates receiving prebiotics showed a larger number of stools over all the duration of dietary intervention compared to that of those on placebo (Repeated Measures ANOVA p < 0.001; day 28 3.4 +/- 0.0.9 vs 1.7 +/- 0.9, respectively; Dunn test p < 0.05). Neonates whose formula was supplemented with prebiotics showed a lower transcutaneous bilirubin that was statistically significant from 72 h of life (5.46 +/- 1.6 vs 7.07 +/- 2.49, post hoc Dunn test, p < 0.05) throughout the duration of the dietary intervention (day 28 2.41 +/- 0.4 vs 2.85 +/- 0.5, post hoc Dunn test, p < 0.05). CONCLUSION: The addition of prebiotics to standard infant diet might represent a novel strategy to help control neonatal hyperbilirubinaemia.

Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients.

Myeloid sarcoma (MS) is a rare neoplasm whose knowledge is largely based on case reports and/or technically dated contributions. Ninety-two MSs in adulthood with clinical data available were evaluated both morphologically and immunohistochemically. Seventy-four cases were also studied by fluorescent in situ hybridization on tissue sections and/or conventional karyotyping on bone marrow or peripheral blood. Histologically, 50% of the tumors were of the blastic type, 43.5% either monoblastic or myelomonocytic and 6.5% corresponded to different histotypes. CD68/KP1 was the most commonly expressed marker (100%), followed by myeloperoxidase (83.6%), CD117 (80.4%), CD99 (54.3%), CD68/PG-M1 (51%), CD34 (43.4%), terminal-deoxy-nucleotidyl-transferase (31.5%), CD56 (13%), CD61/linker for activation of T cells (2.2%), CD30 (2.2%) and CD4 (1.1%). Foci of plasmacytoid monocyte differentiation were observed in intestinal cases carrying inv16. Chromosomal aberrations were detected in about 54% of cases: monosomy 7(10.8%), trisomy 8(10.4%) and mixed lineage leukemia-splitting (8.5%) were the commonest abnormalities, whereas t(8;21) was rare (2.2%). The behavior was dramatic irrespective of presentation, age, sex, phenotype and cytogenetics. Most if not all, long survivors received bone-marrow transplantation. The present report expands the spectrum of our knowledge showing that MS has frequent monoblastic/myelomonocytic differentiation, displays distinctive phenotypic profile, carries chromosomal aberrations other than t(8;21), and requires supra-maximal therapy.

Glomus coccygeum: a review.

With limited information about the coccygeal glomus found in classic textbooks, we deemed it necessary to review the subject. The illustrations presented in this article derive from four coccygeal glomera incidentally encountered during examination of pilonidal disease specimens. Familiarization with its microanatomical features may help to avoid inappropriate interpretation of this enigmatic structure.

Postchemotherapy residual masses in germ cell tumor patients: our experience.

BACKGROUND: The nature of post-chemotherapy tumor residuals can be determined only by excision and histological examination, but at present no consensus has been reached as to whether all patients with residual masses should undergo adjunctive surgery. PATIENTS AND METHODS: Between August 1991 and September 2004, 120 patients with metastatic germ cell tumors were diagnosed at our hospital and 35 of these patients (30%) underwent adjunctive surgery after cisplatin-based chemotherapy. If serum tumor markers were still raised salvage chemotherapy was administered. RESULTS: At the time of surgical intervention 30 patients (86%) had a partial remission with normal markers. Necrosis, differentiated teratoma and undifferentiated tumor were found in nine (30%), 19 (63%) and two (7%) of all patients. Five patients (14%) underwent postchemotherapy resections after second-line cisplatin-based combination chemotherapy. Four of the 35 patients died as a result of their malignant germ cell tumor. The median observation time after the initial diagnosis was 99 months (range 15-172 months). CONCLUSIONS: Secondary resection of residual masses after first or second-line chemotherapy is still an essential part of the treatment of metastatic testicular cancer. Resection of mature teratoma or viable cancer adds to long-term event-free and overall survival in these patients.

"Second hit" in sebaceous tumors from Muir-Torre patients with germline mutations in MSH2: allele loss is not the preferred mode of inactivation.

Muir-Torre syndrome is an autosomal-dominant inherited disorder predisposing to both sebaceous skin tumors and internal neoplasms. In a significant proportion of Muir-Torre syndrome patients skin tumors exhibit microsatellite instability as a hallmark of hereditary nonpolyposis colorectal cancer. Most individuals predisposed to hereditary nonpolyposis colorectal cancer harbor a germline mutation in the DNA mismatch repair genes MSH2 or MLH1. In Muir-Torre syndrome the vast majority of germline mutations have been identified in MSH2. Microsatellite instability in tumor tissue develops after somatic inactivation of the corresponding second mismatch repair allele ("second hit"). So far, the mechanisms of somatic inactivation of the second allele in microsatellite instability positive tumors from patients with known mismatch repair germline mutations are not well understood. We examined whether allele loss (loss of heterozygosity) is a frequent mechanism for inactivation of the second MSH2 allele in a sample of nine microsatellite instability positive skin tumors from eight unrelated Muir-Torre patients with known MSH2 germline mutations. Loss of heterozygosity was determined using microsatellite markers or heteroduplex analysis, respectively. Only one of the nine skin tumors exhibited loss of heterozygosity at the MSH2 locus. Thus, we could show in a sample of sebaceous tumors from patients with genetically proven Muir-Torre syndrome that loss of heterozygosity most probably is not the preferred mode of somatic inactivation of the second MSH2 allele.

Extraventricular neoplasms with neurocytoma features. A clinicopathological study of 11 cases.

The clinicopathological features of a series of neuronal and mixed neuronal and astrocytic neoplasms of the CNS are described. Patients were aged 5 to 63 years. Six cases were composed predominantly of small round cells with clear cytoplasm resembling central neurocytoma but lacked the characteristic intraventricular location of that tumor. The remaining five cases had similar neurocytomatous features associated with a benign astrocytic component. Ganglion cells and hyalinization vessels were observed in both groups. The growth fraction evaluated with monoclonal antibody Ki67Mib1 was low, ranging from 1 to 1.5%. Immunohistochemical detection of synaptophysin played a crucial role in identifying the neuronal nature of these neoplasms and was instrumental in distinguishing them from oligodendrogliomas, with which they are readily confused. The neuronal nature of the oligodendroglial-like cells was confirmed ultrastructurally in one case. The present cases, together with others reported previously, suggest that neoplasms of the CNS with "neurocytic" components are more frequent than generally assumed and expand the morphologic spectrum of neuronal and mixed neuronal-glial tumors. Except for one patient who died postoperatively, all patients were alive at follow-up ranging from 6 to 80 months.

Lipomatous myofibroblastoma: a potential diagnostic pitfall in the spectrum of the spindle cell lesions of the breast.

We report on two cases of myofibroblastoma (MFB) of the breast comprised predominantly of a mature fatty component, representing approximately three quarters of the entire tumour area. Both tumours consisted of a well-circumscribed lipomatous tumour mass containing dispersed nodular or irregularly shaped spindled cellular areas. The fatty component was represented exclusively by mature adipocytes, uniform in size and shape, lacking nuclear pleomorphism. The cellular areas contained spindly to oval cells with morphological and immunophenotypical features typical of MFB. The two components were so intimately admixed that a finger-like infiltrating growth pattern was apparent. The cases reported here as "lipomatous MFB" aim to clarify further the morphological spectrum of MFB of the breast. Lipomatous MFB may potentially mimic other benign or aggressive tumour-like lesions or even bland-looking malignant spindle cell tumours such as fibromatosis, nodular fasciitis, spindle cell lipoma, spindle cell liposarcoma, spindle cell variant of metaplastic carcinoma, spindle cell malignant myoepithelioma, and low-grade fibrosarcoma/malignant fibrous histiocytoma. The histogenesis of the present bimorphic mesenchymal tumours could be explained as the result of a dual, myofibroblastic and lipomatous, differentiation from a common pluripotential mesenchymal precursor cell, probably represented by the vimentin+/CD34+ fibroblast of the mammary stroma.

Percutaneous ethanol injection of large thyroid cystic nodules.

To evaluate the effect of percutaneous ethanol injection (PEI) in the treatment of large compressive thyroid cystic nodules (TCN), we studied 20 patients, potential candidates for surgery (tracheal displacement, nodule volume over 10 mL at ultrasonography) and not cured by aspiration alone: 14 experienced a recurrence after two complete evacuations of cystic fluid (watery nodules, WN); in six an aspiration was impossible because the cystic fluid was very thick (viscous nodules, VN). To exclude malignancy, both cytocentrifugate from WN and the smears from VN were examined. WN were treated with 1-4 sessions of conventional PEI; in VN a first PEI session was performed with the purpose of reducing the density of cystic fluid; then if cystic fluid was successfully aspirated, one or more PEI sessions were performed. Thyroid palpation, ultrasonography with nodule volume assessment, and assays for FT3, FT4, and TSH were performed 1 and 6 months after the last PEI. At month 6, 17 patients (85%) had volume reduction of more than 90% of the initial nodule volume; in 2 patients (10%) there was a reduction between 50 and 90%, and in one patient (5%) an appreciable swelling persisted after 3 injections. Nodule volume was significantly decreased below baseline at month 1 (10.9 +/- 13.3 vs 39 +/- 24 mL, p < 0.001), with a further reduction at month 6 (5 +/- 11.7 mL, p < 0.01 vs 1st month value). In most of the nodules the cystic portion completely disappeared; the residual tissue showed fibrous features, often with calcifications. In 11 patients follow-up was prolonged over the sixth month (15 +/- 4 months); the nodule volume did not significantly differ from the sixth month (3 +/- 2.2 mL) and the end of the follow-up (2.8 +/- 2.3 mL). In conclusion, we demonstrate that PEI may be a safe and effective procedure in the treatment of large TCN.

Percutaneous ethanol injection may be a definitive treatment for symptomatic thyroid cystic nodules not treatable by surgery: five-year follow-up study.

We present a prospective study on the long-term efficacy of percutaneous ethanol injection (PEI) treatment for thyroid cystic nodules. Among patients referred for symptomatic thyroid cystic nodules who had relapsed after two aspirations or whose nodules could not be aspirated due to the thickness of the cystic fluid, PEI was given when surgery was either refused or contraindicated. Forty-three patients were treated; the mean basal volume of the cysts was 38.4 mL. The purpose of the study was to evaluate long-term efficacy of PEI treatment on: (1) amelioration of symptoms and signs of local compression and (2) nodule volume reduction. In three subjects (7%), PEI failed to induce a significant (>50%) nodule reduction, so that surgical treatment was performed. In 40 patients (93%), an impressive nodule shrinkage was observed, reaching a plateau after 24 months (volume reduction = 91.9%+/-11.4%). A new PEI session was needed in two patients in whom a recurrence was noted within the first 6 months. After 6 months, no significant (> or =1 mL volume) nodule regrowth was observed up to 60 months. Both symptoms and tracheal displacement rapidly (within 1 month) and significantly (p<0.01) improved. After PEI, mild pain was the only side effect observed. No suspicious cytology was observed in any residual nodule greater than 1 mL 6 and 24 months after the last PEI session. Our data suggest that PEI is a first-line safe, effective, probably definitive, treatment for cystic thyroid nodules for which surgery is either refused or contraindicated.

Osteochondroma of the L-5 vertebra: a rare cause of sciatic pain. Case report.

Solitary or multiple osteochondromas, which are benign bone tumors that usually occur in the long bones, are rarely found in the vertebral column. When present in the spine, however, they have a predilection for the cervical or upper thoracic regions. The authors present the case of a solitary osteochondroma arising from the left L-5 articular process that contributed to sciatica; complete cure was achieved following its removal. It is possible to speculate that the cartilage of secondary ossification centers can be the origin of aberrant islands of cartilaginous tissue that cause the osteochondroma to form. The more rapid the ossification process of these centers, the greater the probability that aberrant cartilage will form. Therefore, the fact that osteochondromas are more frequently located in the higher segments of the vertebral column could be explained by the different durations of the ossification processes in these centers, which increase gradually below the cervical segments.

Muscular hamartoma of the breast. Case report and review of the literature.

Muscular hamartoma (MH) is a rare tumor-like lesion of the breast, and only 22 cases have been reported in the literature. We report an additional case of MH of the breast, giving a new immunocytochemistry-based insight into the histogenesis of the smooth muscle component. The expression of CD34 antigen in smooth muscle cells suggested that MH originates from stromal cells via leiomyomatous metaplastic changes. This hypothesis was supported by the evidence that stromal cells in the normal parenchyma nearby the hamartoma were positive for CD34 antigen and, focally, also positive for smooth muscle markers (alpha-smooth muscle actin and desmin). A complete list of differential diagnoses and a review of the literature on the topic are provided. Although the use of the term "muscular hamartoma" could be considered inappropriate because of the absence of smooth muscle tissue in the normal breast, the authors underline that this designation can be easily accepted if the histogenesis of the heterologous component is regarded as a result of a stromal cell metaplastic change.

Benign spindle cell tumors of the mammary stroma: diagnostic criteria, classification, and histogenesis.

Purely benign mesenchymal spindle cell neoplasms of the breast are currently labeled under various terms in the literature (benign spindle cell tumor, fibroma, spindle cell lipoma, myofibroblastoma, solitary fibrous tumor, myogenic stromal tumor). The lack of strict diagnostic criteria to clearly indicate such mesenchymal neoplasms is the main reason which generated the risk of terming the same lesion under different names or, conversely, of collecting different types under the same term. Although such neoplasms exhibit morphological and immunophenotypical heterogeneity, they actually represent variations of the same tumor entity, likely arising from the uncommitted vimentin+/CD34+ fibroblasts of the mammary stroma, capable of multidirectional mesenchymal differentiation. To cover the entire spectrum of such lesions, the term "benign spindle cell tumors (BSCTs) of the mammary stroma" is advocated. BSCTs can be subtyped into four main groups by light microscopy (LM) and immunocytochemistry (ICC): fibroblastic, myofibroblastic, fibrohistiocytic, and mixed forms. A simple and practical approach to a nosologically correct diagnosis and a list of differential diagnoses are presented. The awareness of the diversity of morphological and immunophenotypical features of BSCTs of the mammary stroma, including uncommon variants, is helpful to avoid confusion with other monomorphic bland-looking benign and malignant spindle cell tumors and tumor-like lesions of the breast.

Congenital mesoblastic nephroma: report of a Case with review of the most significant literature.

AIMS AND BACKGROUND: Congenital mesoblastic nephroma (CMN) is a rare pediatric tumor of the kidney with the highest peak of incidence during the first 3 postnatal months. It has previously been confused with Wilms' tumor (which, on the contrary, is rare during the first six months of age and is still considered a histogenetic congener). CMN almost always has a favourable prognosis. Therefore, CMN needs to be correctly diagnosed and differentiated from other pediatric renal neoplasms. Two morphological subtypes are currently distinguished histologically: the classical or leiomyomatous type and the atypical or cellular type. Mixed forms with a combination of the two patterns are also on record. Recurrence and even tumor-related death have been described in the literature and always related to the atypical form or to the mixed form, particularly in patients aged more than 3 months and in those cases in which the surgical removal was not complete. Opinions concerning post-surgical clinical management, especially in regard to adjuvant therapy, are not unanimous. METHODS: A case of CMN, predominantly of the classical histological subtype diagnosed in a baby with a follow-up of 6 years, is herein presented. The tumor was discovered at birth and surgically removed after one month. Since the tumor showed a high mitotic index (one of the characteristics of the cellular subtype) and the perirenal fat was focally involved with the tumor, the possibility of giving adjuvant chemotherapy was considered. Flow cytometric analysis was also performed which showed a diploid DNA content of neoplastic cells. RESULTS: The tumor was completely removed, surgical margins were free histologically, and no clear-cut histological features of the atypical subtype were noted. Flow cytometrically, it showed the euploid DNA content. Consequently no additional therapy was given. Six years after surgery the patient is developing well and is free of disease. He has regular follow-up examinations. CONCLUSIONS: CMN almost always pursues a benign clinical course if diagnosed under three months of age and if totally surgically excised independent of histological type. Criteria for management of atypical cases are not unanimous in regard to the benefit of additional therapy after surgery.

Surgical treatment of anterior callosal tumors.

OBJECTIVE: Thirteen patients with neoplasm of anterior corpus callosum have undergone our observation during the last two years. METHODS: For the diagnosis, all the patients underwent TC, NMR and stereotactic biopsy. In 6 cases with glioblastomas, a radiation treatment was adopted. The other 7 patients underwent total surgical treatment in 5 cases, and partial in 2 cases, as documented by postoperative contrast-enhanced CT scanning. Histologically, there were: 3 glioblastomas, 1 grade III astrocytoma, 1 neuroblastoma (PNET), 2 pilocytic astrocytomas. RESULTS: Neuropsychological tests carried out on the 5 patients still living showed persistent disturbances of verbal memory in all five and disturbances of verbal phonological fluency in 3 cases. No patient presented apraxia, dysgraphia and dyslexia. CONCLUSIONS: Thus, no severe neuropsychological deficits developed after surgical treatment of anterior callosal tumors.

Preoperative embolization in surgical treatment of spinal thoracic dumbbell schwannoma. A case report.

Schwannoma is the most common intraspinal tumor, which at times goes out of spinal canal and spreads into the paraspinal tissue to produce a dumbbell configuration. A 58-year-old woman is reported, in whom a plain thorax X-rays accidentally disclosed a mass located in the posterior mediastinum. Computerized tomography (CT) revealed a dumbbell lesion, 4.5 cm in diameter, in the right rib-vertebral groove at the T9 level. Spinal angiography showed localization of Adamkievicz artery at the T10 level on the left side. The lesion appeared hypervascular and was embolized by particulate agents (Contour Emboli 150-250 mu) with reduction of its blush. A combined two-team (thoracic and neurosurgeon) approach permitted an uneventful removal of a schwannoma.

Metaplastic breast carcinoma with epithelial phenotype of pseudosarcomatous components.

A case of metaplastic breast carcinoma was subjected to an immunohistochemical study to characterize its apparent fibrosarcomatous and chondrosarcomatous elements. Polyclonal and monoclonal antibodies against epithelial cell components such as keratin proteins, epithelial membrane antigen, membrane and cytoplasmic antigens of human mammary carcinoma cells, and carcinoembryonic antigen were used, as well as antibodies against the mesenchymal antigens, desmin, and vimentin. The cells with a mesenchymal appearance had an epithelial derivation, as shown by the presence of epithelial cell markers and absence of mesenchymal cell markers.