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PubMed2000

Embryonal tumors in the adult population: implications in therapeutic planning.

The natural history of neuroectodermal tumors is still debated as far as prognostic factors are concerned; the same uncertainty applies to the optimal radiotherapy schedule and even more to the presumptive additive effect of chemotherapy. The rarity of these tumors and the heterogeneity of management make interpretation of literature data also more difficult. We evaluated clinical course in a cohort of 39 patients, including 31 with medulloblastoma (MB) and 8 with primitive neuroectodermal tumors (PNET). All patients were treated with radiotherapy, a standardized chemotherapy protocol including PCV scheme, and a second-line chemotherapy with cisplatin and etoposide (VP16) at recurrence. In 27 patients, intrathecal chemotherapy was also delivered. Median follow-up was 10.8 years. Overall, PNET had a worse outcome as compared to MB: median survival times were 42.8 vs. 92.6 months, respectively (p = 0.05). At 5 years, 45% of MB patients are alive. No significant difference in disease-free period was found between patients of different age, desmoplastic variant, tumor localization, or extent of surgery. Patients considered to be "high risk" had a significantly shorter disease-free period as compared with low-risk patients (27 vs. 54.7 months, p = 0.04). Systemic or intrathecal chemotherapy did not influence progression-free survival (PFS). However, in the majority of chemotherapy-treated patients, a low-dose craniospinal radiotherapy was also delivered. This combination of treatments may have avoided the expected increased percentage of failure. Moreover, more than half of recurrent patients had a partial response to chemotherapy that extended survival for approximately 3 years. Repeated surgery and chemotherapy at recurrence favorably influenced survival time.

Adult↗
PubMed1982

[Surgical treatment of Prinzmetal's angina pectoris by plexectomy associated with aortocoronary bypass. Apropos of 56 cases].

The results of coronary bypass surgery are generally not as good in Prinzmetal angina as in classical angina pectoris. The percentage of myocardial infarction, recurrent angina and death is much higher. One reason for these failures could be the persistence of coronary spasm. In order to prevent this, denervation of the pre-supra and retro aortic nerve plexuses was carried out in 56 patients (54 male, 2 female) with Prinzmetal angina and operable coronary arterial lesions. Forty patients had documented coronary spasm mainly of the left anterior descending (20 cases) or the right coronary artery (13 cases). Surgery consisted of cardiac denervation associated with direct myocardial revascularisation by implantation of I (37 cases), 2 (13 cases) or 3 (6 cases) aorto coronary bypass grafts. Two deaths were observed in the perioperative period (one low output syndrome and one severe arrhythmia) and one myocardial infarction in the postoperative period. Of the 54 survivors, 49 are asymptomatic and 2 have recurrent spontaneous angina. Exercise electrocardiography in 44 patients was negative in 40 cases. Continuous electrocardiographic recordings (Holter method) in 33 patients was negative for ischemia and of 25 bypass grafts controlled, 24 were patent. Seventy five methylergometrine provocation tests were performed: only 2 were positive, both in patients with recurrent attacks. Therefore, with respect to the total numbers of recurrent angina (2), post operative infarction (I), peri and post operative deaths (3), the percentage of poor results was only 10,7 p. 100, almost three times lower than in previously reported series. In conclusion, we can say that the association of cardiac denervation with coronary bypass surgery significantly improves the percentage of good results (89,3 p. 100 of patients presenting with Prinzmetal angina).

Adult↗
PubMed1986

[Differing progress patterns in cancer of the uterine cervix and variant effects of adjuvant chemotherapy based on histological type].

Clinical features of 644 surgically treated cases of cancer of the uterine cervix were analyzed according to their histological type. Large cell non-keratinizing carcinomas (L) showed node metastasis proportional to the grade of invasion in the cervix, and the lowest recurrence rate. Small cell non-keratinizing carcinomas (S) tended to have widely spread metastasis from an early stage of the primary lesion. Lateral recurrence from metastatic foci was common in this type. Keratinizing carcinomas (K) were localized in the cervix until the primary tumor became enlarged to a certain size. Central recurrence from invasive foci in the surrounding tissue or organ occurred more often than lateral recurrence in this type. Metastasis pattern of pure adenocarcinomas (A) was similar to that of S, but recurrence was delayed. Adenosquamous carcinomas (AS) showed a similar metastasis pattern to that of K, but recurrence was rapid and the ratio high. Prophylactic maintenance chemotherapy with Tegafur (800 mg/day) or Carboquone (0.5 mg/day) was performed in 187 cases for a period of 2 years after surgery. The effect of maintenance chemotherapy depended on the histological type. A marked effect was obtained in the groups of S and A, in which no recurrence has appeared so far. The recurrence rate of L dropped to 1/5 that of the control. However, unsatisfactory results were shown in the groups of K and AS including the keratinizing cell component. It is of significance that maintenance chemotherapy showed the highest effectiveness in S and A on which conventional adjuvant therapy, i.e. postoperative radiotherapy, has had the least effect. This has led us to consider that a proper selection of adjuvant therapies would contribute toward improving the postoperative prognosis of patients with cancer of the uterine cervix.

Adenocarcinoma↗
PubMed2005

MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever.

Autosomal recessive autoinflammatory disorder caused by mutations of the mevalonate kinase gene (MVK), leading to mild, incomplete MK enzyme deficiency (MKD), has been known so far as Hyper-IgD and periodic fever syndrome (HIDS) and regarded as mostly occurring in Northern Europe. Here we report the results of the molecular characterization of the first Italian series of patients affected with autoinflammatory disorders and periodic fever. A total of 13 different mutations, scattered throughout the MVK coding region, were identified in either homozygous or compound heterozygous state in 15 patients. The mutation leading to the V377I amino-acid change, already described also in other series, resulted the most common with a frequency of 50% of all MKD alleles. Among the other mutations, eight had never been described before, including an interstitial deletion of 19 nucleotides in exon 2. In addition to these nucleotide changes, private and polymorphic MVK variants have been detected in the patients under analysis and checked also in a set of control individuals. Clinical features are reported for each of the 15 MKD patients, and life-threatening infections and systemic amyloidosis presented as unexpected MKD-related complications. Our study demonstrates that MKD is a common cause of recurrent fever also in the Italian population, where it is associated with both a wide spectrum of previously unreported MVK mutations and peculiar phenotypic features.

Adolescent↗
PubMed2001

Altered respiratory tissue mechanics in asymptomatic wheezy infants.

Low-frequency forced oscillation (LFOT) and raised volume rapid thoracic compression (RVRTC) techniques were used to measure airways and respiratory tissue mechanics and forced expiratory volumes in 24 asymptomatic infants with recurrent wheeze. Total respiratory impedance spectra (Zrs) (0.5 to 20 Hz) were obtained (n = 22) and a model containing airway (resistance [Raw] and inertance [Iaw]) and constant-phase tissue (tissue damping [G] and tissue elastance [H]) compartments fitted to Zrs. Forced expiratory volumes (FEV(0.5)) were determined (n = 16). Standardized variants (Z scores) were calculated for comparison to a healthy population (Hall et al., Am J Respir Crit Care Med 2000;162:1397-1402). Wheezy infants had elevated H (Z scores: 0.61 +/- 0.20; p = 0.007) but not Raw (0.14 +/- 0.25; p > 0.2), G (0.41 +/- 0.21; p = 0.066), or FEV(0.5) (-0.25 +/- 0.25; p > 0.2) compared with healthy infants. Infants younger than 1 yr of age were not significantly different from normals, whereas lung function from infants older than 1 yr had deviated from normal infants, with Z scores of 0.58 +/- 0.2 (p = 0.018), 0.79 +/- 0.31 (p = 0.032), 1.06 +/- 0.25 (p = 0.002), and -0.94 +/- 0.22 (p = 0.007) for Raw, G, H, and FEV(0.5) respectively. We conclude that asymptomatic infants with recurrent wheeze have altered lung function. The abnormalities were more pronounced in respiratory tissue mechanics than in airway mechanics or forced volumes, highlighting the value of techniques capable of partitioning lung function into airway and respiratory tissue components.

Child, Preschool↗
PubMed2006

Specific features of differentiated thyroid carcinoma in patients over 70 years of age.

BACKGROUND AND OBJECTIVES: Among the geriatric population, there is a lower incidence of thyroid carcinoma (TC), but it accounts for 30% of all thyroid disorders compared to 6-8% in younger subjects. Prognosis, moreover, is worse in the elderly, as demonstrated by the fact that 81% of deaths related to these tumors occur in patients over 55. The aim of this retrospective study was to identify the characteristics of differentiated thyroid carcinoma (DTC) peculiar to the elderly. METHODS: Of 638 patients who underwent surgery for DTC over a period of 30 years, 46 were more than 70 years old. All the elderly patients had undergone radioioidine and TSH-suppression therapy following surgical resection. RESULTS AND CONCLUSIONS: Despite these measures, the rate of recurrence was 26.5% at 5 years and 63.6% at 10 years. The 5- and 10-year disease-specific survival rates were 87.8% and 63.6%, respectively. On an average, survival was 55.1 months when death was disease-related, and with regard to histological type, it was longer in papillary carcinoma than in the follicular variant, and longest of all in occult sclerosing carcinoma. Survival was greatest in patients with tumors less than 2 cm in diameter, characterized by the absence of extraglandular spread and by lymph node metastasis.

Adolescent↗
PubMed1987

Restenosis and its determinants in first and repeat coronary angioplasty.

Restenosis is the main problem limiting long-term success of percutaneous transluminal coronary angioplasty (PTCA) and is most accurately evaluated by follow-up angiography. We compared the primary and long-term results of angioplasty in 268 consecutive patients (293 segments) with first PTCA (PTCA 1, angiographic follow-up 98%) and in 66 patients (76 segments) with repeat PTCA after restenosis (PTCA 2, angiographic follow-up 92%). Forty clinical, angiographic and procedural factors were assessed in relation to outcome. Primary success rate was higher in PTCA 2 (91% vs 67.5%) and major complications were fewer (4.5% vs 16%). Higher inflation pressure (7.9 +/- 2.3 vs 6.8 +/- 1.8 atm, P less than 0.005) and larger balloons (3.5 +/- 0.5 vs 3.2 +/- 0.5 mm, P less than 0.005) were used for PTCA 2, resulting in lesser residual stenosis (33 +/- 16% vs 40 +/- 18%, P less than 0.05). Restenosis rate (greater than or equal to 70%) after PTCA 1 and after PTCA 2 (27% vs 36%, P = NS) and the mean time to recurrence (4.7 vs 5.3 months, P = NS) were similar. Procedural factors were the main determinants of long-term success in primary PTCA. The restenosis risk was independently related to residual stenosis greater than or equal to 45% (P less than 0.001), variant angina (P less than 0.05) and multivessel disease (P less than 0.05) after PTCA 1 and to male sex (P less than 0.001) and higher inflation pressure (P less than 0.05) after PTCA 2. Mild to moderate intimal tearing was associated with less restenosis after PTCA 1, but not after PTCA 2. Including 9 patients (10 segments) with a third PTCA, 70% of the 66 patients with repeat PTCA had a successful long-term outcome. Repeat angioplasty should therefore be considered as an integral part of PTCA therapy. Restenosis however remains a major concern. An optimal primary result with a minimal residual stenosis is decisive for first PTCA, whereas avoidance of a dissection by using lower inflation pressure on a restenosis might improve the long-term outcome of repeat PTCA.

Adult↗
PubMed1985

Hexosaminidase-A deficiency presenting as atypical juvenile-onset spinal muscular atrophy.

Three patients from two families had an unusual phenotypical variant of late-onset hexosaminidase-A deficiency. The clinical picture was dominated by spinal motor neuron involvement mimicking juvenile-onset spinal muscular atrophy. Atypical features included prominent muscle cramps, postural and action tremor, recurrent psychosis, incoordination, corticospinal and corticobulbar involvement, and dysarthria. The presence of these atypical features in patients whose lower motor neuron involvement would otherwise be consistent with juvenile-onset spinal muscular atrophy should raise the suspicion of the presence of hexosaminidase-A deficiency and GM2 gangliosidosis that can be proved by appropriate enzyme assays.

Adult↗
PubMed1995

Cellular immortality: a late event in the progression of human squamous cell carcinoma of the head and neck associated with p53 alteration and a high frequency of allele loss.

Many human tumors contain variant cells that, unlike their normal counterparts, possess indefinite proliferative potential in vitro. However, little is known of the relevance of these immortal cells to human carcinomas in vivo. To investigate immortality in a human tumor system, we established cultures from different stages of head and neck squamous carcinoma (SCC-HN). All the neoplastic cultures were transformed because they showed very low cornification in surface or suspension culture and were partially or completely resistant to suspension-induced death. Immortal variants were not detected in premalignant erythroplakia cultures, but their frequency increased with tumor progression, indicating that immortality is a late event in carcinogenesis. Some late-stage carcinomas still produced senescent cultures, but, significantly, all recurrent tumors were immortal. Immortal but not senescent carcinoma cultures were associated with p53 dysfunction and a high frequency of allele loss, indicative of tumor suppressor gene inactivation. These results show that there are at least two classes of human SCC-HN that are phenotypically and genotypically distinct and that the pathological stage of a given tumor is not necessarily indicative of the kind of cells it contains.

Aneuploidy↗
PubMed2004

Molecular pathogenesis of meningiomas.

Meningiomas are common central nervous system tumors that originate from the meningeal coverings of the brain and the spinal cord. Most meningiomas are slowly growing benign tumors that histologically correspond to World Health Organization (WHO) grade I. However, certain rare histological variants (clear cell, chordoid, papillary, and rhabdoid), as well as atypical (WHO grade II) and anaplastic (WHO grade III) meningiomas show a more aggressive biological behavior and are clinically associated with a high risk of local recurrence and a less favorable prognosis. This review summarizes the most important features of meningioma pathology and provides an up-to-date overview about the molecular mechanisms involved in meningioma initiation and progression. Current data indicate that meningioma initiation is closely linked to the inactivation of one or more members of the highly conserved protein 4.1 superfamily, including the neurofibromatosis type 2 gene product merlin/schwannomin, protein 4.IB (DAL-1) and protein 4.1R. The genetic alterations in atypical meningiomas are complex and involve losses on 1p, 6q, 10, 14q and 18q, as well as gains on multiple chromosomes. The relevant genes are still unknown. Anaplastic meningiomas show even more complex genetic alterations, including frequent alteration of the CDKN2A, p14ARF, and CDKN2B tumor suppressor genes at 9p21, as well as gene amplification on 17q23. A better understanding of the molecular mechanisms involved in meningioma pathogenesis may not only lead to the identification of novel diagnostic and prognostic marker but will also facilitate the development of new pathogenesis-based therapeutic strategies.

Animals↗
PubMed2004

Endoscopic management of adenoma of the major duodenal papilla.

BACKGROUND: It is well established that adenoma of the major duodenal papilla has a potential for malignant transformation. Standard treatment has been surgical (duodenotomy/local resection, pancreaticoduodenectomy). Endoscopic management is described, but there is no established consensus regarding the approach to papillectomy or the need for surveillance. This study describes endoscopic management and long-term follow-up of papillary tumors by 4 groups of expert pancreaticobiliary endoscopists. METHODS: Consecutive patients with papillary tumors referred to 4 pancreaticobiliary endoscopy centers for evaluation for endoscopic papillectomy were reviewed. For each patient, an extensive questionnaire was completed, which included 19 preoperative and 15 postoperative data points. A total of 103 patients (53 women, 50 men, age range 24-93) who underwent attempted endoscopic resection were included. Of these, 72 had sporadic adenoma, and the remaining patients had familial adenomatous polyposis, including Gardner's variant. Presenting symptoms were jaundice/cholangitis/pain (n=59), pancreatitis (n=18), and bleeding (n=12). Twenty-six patients were asymptomatic. RESULTS: Endoscopic treatment was successful, long term, in 83 patients (80%) and failed (initial failure or recurrent tumor) in 20 (20%) patients. Success was significantly associated with older age (54.7 [16.6] vs. 46.6 [21.7] years; p=0.08) and smaller lesions (21.1 [8.3] vs. 29.7 [7.2] mm; p<0.0001). Success rate was higher for sporadic lesions compared with genetically determined lesions (63 of 72 [86%] vs. 20 of 31 [67%]; p=0.02). There were 10 initial failures, which was more common for sporadic lesions (7 of 10). The overall success rate for papillectomy was similar in patients who had adjuvant thermal ablation (81%) compared with those who did not (78%). However, recurrence (n=10) was more common in the former group (9 of 10, [90%]; p=0.22). Complications (n=10) included acute pancreatitis (n=5), bleeding (n=2), and late papillary stenosis (n=3). Acute pancreatitis was more common in patients who did not have pancreatic duct stents placed (17% vs. 3.3%). Papillary stenosis was more frequent without short-term pancreatic duct stent placement (15.4% vs. 1.1%), although the difference was not statistically significant, because this complication was infrequent. CONCLUSIONS: Endoscopic treatment of papillary adenoma in selected patients appears to be highly successful. The majority can undergo complete resection after ERCP. In expert hands, complications are infrequent and may be avoided by routine placement of a pancreatic duct stent.

Adenoma↗
PubMed1983

Spontaneous remission is a frequent outcome of variant angina.

To assess the prevalence of spontaneous remission in variant angina, 100 patients with this diagnosis who had undergone coronary arteriography in the hospital and a follow-up of at least 1 year were studied. Patients with coronary bypass surgery or myocardial infarction were excluded. Remission was diagnosed in 45 of the 100 patients who had been angina-free and had had no treatment for more than 3 months (mean 18.3). The other 55 patients were receiving medical treatment; 37 had been angina-free for at least 6 months (mean 22.5) and angina persisted in 18. The persistent angina group had a lower prevalence of organic coronary stenoses 70% or greater: 4 of 18 versus 22 of 45 and 22 of 37 for the other two groups (p less than 0.05), and a longer history of rest angina before admission. The remission group contained more patients (17 of 45 versus 4 of 55 [p less than 0.001]) whose attacks had been documented only by provocative testing. Rest angina recurred when calcium antagonist drugs were discontinued in 15 of 51 instances, within 1 month in 11 patients and later in 4 patients. Remission was eventually attained in 35 of the 38 patients in whom these drugs were stopped. These results indicate that remission is a frequent outcome of variant angina. This fact should be considered in the evaluation of the long-term results of treatment and in the planning of care for an individual patient.

Adult↗
PubMed2001

Acute, severe self-limiting dysautonomia and hypertensive encephalopathy.

We describe two unrelated children with almost identical clinical illnesses comprising of severe, burning dysesthesia, allodynia, hypertensive encephalopathy, and laboratory evidence of both sympathetic and parasympathetic autonomic disturbance after a nonspecific viral illness. No underlying etiology was identified. Both patients displayed complete resolution of their clinical and radiologic findings after a number of months, and there was no recurrence over a follow-up period of 17 months to 4 years. Treatment of the patients' dysesthesias proved difficult, requiring multiple analgesics and intensive physiotherapy. We speculate that their illnesses may represent a pure autonomic variant of Guillain-Barré syndrome.

Acute Disease↗
PubMed2005

Familial nonmedullary thyroid cancer.

Familial nonmedullary thyroid cancer (FNMTC) is a syndrome of familial clustering of thyroid cancers of follicular cell origin. It is characterized by multifocality, early onset, more recurrences, and a higher degree of aggressiveness than nonfamilial thyroid cancers of follicular cell origin. An autosomal dominant inheritance pattern with reduced penetrance appears likely in most pedigrees. Although several candidate genes responsible for isolated clinical variants of FNMTC have been identified in single families, the gene(s) responsible for the vast majority of FNMTC cases has yet to be identified. Members of FNMTC cohorts should be followed longitudinally with physical examination and ultrasonography, and aggressively treated when cancer is diagnosed. When cancer is diagnosed, total thyroidectomy should be performed, and most patients should have a prophylactic central neck dissection and a therapeutic lateral functional neck dissection, postoperative radioiodine ablation and thyroid-stimulating hormone (TSH) suppressive therapy. Close follow-up with stimulated thyroglobulin levels, neck ultrasounds, and radioiodine scans are also central to the management strategy.

Humans↗
PubMed2001

Benign fibrous histiocytoma (dermatofibroma) of the face: clinicopathologic and immunohistochemical study of 34 cases associated with an aggressive clinical course.

Thirty-four cases of fibrous histiocytoma (dermatofibroma) arising on the face are reported. These neoplasms occurred frequently in females (24 female, 10 male) and showed a broad age range (12 to 85 years; mean: 43.6 years, median: 41 years). The neoplasms originated on the forehead (nine cases), the cheek (eight cases), the eyebrow (four cases), the temporal region (three cases), the nose (two cases), and the ear (one case); in seven cases the location face was given only. Five of 27 cases with follow-up information (median: 5 years) recurred locally; in one case four recurrences were excised within 8 years. The majority of cases extended into the subcutis and deep soft tissue including striated muscle (50% of cases). Histologically, only the minority of cases was composed entirely of histiocytoid and spindle-shaped tumor cells arranged in a storiform growth pattern. In many cases cellular fascicles and bundles of spindle-shaped tumor cells were noted in addition to classical morphological features of fibrous histiocytoma. A moderate mitotic rate (mean: 2.97 mitoses in 10 HPFs) was observed, and in few cases increased atypia was evident. Frank tumor necrosis and/or vascular invasion were not identified. Immunohistochemical studies revealed Factor XIIIa positivity in 13 out of 17, focal CD68 positivity in 6 out of 10, and alpha-smooth muscle actin positivity in 16 out of 19 cases tested. These lesions should be distinguished from dermatofibrosarcoma protuberans, including its fibrosarcomatous variant, leiomyosarcoma, and low-grade myofibroblastic sarcoma. Cases of fibrous histiocytoma of the face have to be excised with wider margins in comparison with examples of classical fibrous histiocytoma occurring on the extremities because of diffuse infiltration, involvement of deeper structures, and an increased rate of local recurrences.

Actins↗
PubMed2006

Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis.

OBJECTIVES: Chronic pancreatitis is a progressive inflammatory disorder leading to irreversible exocrine and/or endocrine impairment. It is well documented that mutations in the cationic trypsinogen (PRSS1) gene can cause hereditary pancreatitis. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) and the serine protease inhibitor Kazal type 1 (SPINK1) genes are also associated with pancreatitis. METHODS: We analyzed 381 patients with a primary diagnosis of chronic or recurrent pancreatitis using the Ambry Test: Pancreatitis to obtain comprehensive genetic information for the CFTR, SPINK1, and PRSS1 genes. RESULTS: The results identified 32% (122/381) of patients with 166 mutant CFTR alleles, including 12 novel CFTR variants: 4375-20 A>G, F575Y, K598E, L1260P, G194R, F834L, S573C, 2789 + 17 C>T, 621+83 A>G, T164S, 621+25 A>G, and 3500-19 G>A. Of 122 patients with CFTR mutations, 5.5% (21/381) also carried a SPINK1 mutation, and 1.8% (7/381) carried a PRSS1 mutation. In addition, 8.9% (34/381) of all patients had 1 of 11 different SPINK1 mutations. Another 6.3% (24/381) of the patients had 1 of 8 different PRSS1 mutations. Moreover, 1.3% of the patients (5/381) had 1 PRSS1 and 1 SPINK1 mutation. A total 49% (185/381) of the patients carried one or more mutations. CONCLUSIONS: Comprehensive testing of the CFTR, PRSS1, and SPINK1 genes identified genetic variants in nearly half of all subjects considered by their physicians as candidates for genetic testing. Comprehensive test identified numerous novel variants that would not be identified by standard clinical screening panels.

Acute Disease↗
PubMed2002

Maxillary sinus hypoplasia.

Functional endoscopic sinus surgery (FESS) is now a routine surgical procedure performed all around the world. A pre-operative computed tomography (CT) scan is considered mandatory in most countries where these are available but there are still some surgeons who question the need for imaging especially in patients due to undergo limited FESS or middle meatal antrostomy. There are excellent papers, describing how to read scans looking for anatomical abnormalities, but unfortunately their description of maxillary sinus hypoplasia and the associated uncinate process deformities are limited. This article describes two cases, one of unilateral and one of bilateral maxillary sinus hypopolasia (MSH) and discusses their implications. Awareness of these anatomical variants is crucial to avoid orbital complications.

Endoscopy↗