Examination of micro-superficial lesions of up to 5 mm in size in the pharyngolaryngeal region.

OBJECTIVE: For low-grade intraepithelial neoplasia cases, pharyngolaryngeal lesions equal to or less than 5 mm in size do not generally progress to invasive carcinoma. However, micro-superficial lesions equal to or less than 5 mm that showed rapid growth have been recently encountered. This study aimed to identify the characteristics of preferential progression of lesions equal to or less than 5 mm in size. METHOD: Gross findings, endoscopic findings and pathological results of 55 lesions measuring equal to or less than 5 mm in diameter were retrospectively reviewed to identify factors that distinguish squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions. RESULTS: The overall sensitivity, specificity, accuracy, and positive and negative predictive value of background colouration and intrapapillary capillary loop pattern in differentiation of squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions were all 100 per cent. CONCLUSION: Diagnosis based on background colouration and the intrapapillary capillary loop pattern on narrow-band imaging facilitates the pathological examination of lesions measuring equal to or less than 5 mm.

Differential expression of angiotensin-converting enzyme-2 in human paranasal sinus mucosa in patients with chronic rhinosinusitis.

OBJECTIVE: Severe acute respiratory syndrome coronavirus-2 uses angiotensin-converting enzyme-2 as a primary receptor for invasion. This study investigated angiotensin-converting enzyme-2 expression in the sinonasal mucosa of patients with chronic rhinosinusitis, as this could be linked to a susceptibility to severe acute respiratory syndrome coronavirus-2 infection. METHODS: Ethmoid sinus specimens were obtained from 27 patients with eosinophilic chronic rhinosinusitis, 18 with non-eosinophilic chronic rhinosinusitis and 18 controls. The angiotensin-converting enzyme-2 and other inflammatory cytokine and chemokine messenger RNA levels were assessed by quantitative reverse transcription polymerase chain reaction. Angiotensin-converting enzyme-2 positive cells were examined immunohistologically. RESULTS: The eosinophilic chronic rhinosinusitis patients showed a significant decrease in angiotensin-converting enzyme-2 messenger RNA expression. In the chronic rhinosinusitis patients, angiotensin-converting enzyme-2 messenger RNA levels were positively correlated with tumour necrosis factor-α and interleukin-1ß (r = 0.4971 and r = 0.3082, respectively), and negatively correlated with eotaxin-3 (r = -0.2938). Angiotensin-converting enzyme-2 immunoreactivity was mainly localised in the ciliated epithelial cells. CONCLUSION: Eosinophilic chronic rhinosinusitis patients with type 2 inflammation showed decreased angiotensin-converting enzyme-2 expression in their sinus mucosa. Angiotensin-converting enzyme-2 regulation was positively related to pro-inflammatory cytokines, especially tumour necrosis factor-α production, in chronic rhinosinusitis patients.

Intellectual, adaptive and behavioural characteristics in four patients with 18p deletion syndrome.

BACKGROUND: The association of behavioural phenotype assessment with cytogenomic characterisation may provide a better comprehension of genotype-phenotype correlations in syndromes caused by chromosomal abnormalities, such as 18p deletion syndrome. METHOD: We report on four Brazilian patients with 18p deletion syndrome characterised by cytogenomic techniques and detailed neuropsychological evaluation. Intellectual, adaptive and behavioural characteristics were assessed through the Wechsler's Scales, the Vineland-II Scale and the Child Behaviour Checklist, respectively. Socio-economic measures including main caretaker educational level and family income as defined by Brazilian criteria for social class classification were also collected to evaluate a possible contribution of environmental factors in neurocognitive variability. RESULTS: Two out of four patients showed intellectual disability (IQ < 70). Wechsler's scale results suggest that in our sample, interpretation of social situations based on observation of non-verbal behaviour constitute a cognitive strength while judgement of social rules and language skills associated with word knowledge and verbal fluency may be a cognitive weakness. Concerning adaptive behaviour, motor and socialisation domains showed to better develop than communication and daily living skills on the Vineland-II Scale. Only one patient presented internalising behavioural problems based on the Child Behaviour Checklist. Our results also suggested that socio-economic status may contribute to overall patient development. CONCLUSION: Our results suggest that some 18p deletion syndrome patients may present average intellectual performance and that the segment deletion size and some families' socio-economic conditions may influence cognitive development.

Comparison of arginase isoform expression in patients with different subtypes of chronic rhinosinusitis.

OBJECTIVE: Although human paranasal sinuses are critical organs for nitric oxide production, little information is available regarding the role of arginase in alterations of arginine metabolism and nasal nitric oxide levels that may be informative for classifying chronic rhinosinusitis subtypes. METHODS: The expression and localisation of arginase and nitric oxide synthase isoforms in paranasal sinus mucosa were examined, and the fractional exhaled nitric oxide was measured in chronic rhinosinusitis without nasal polyps (n=18) and chronic rhinosinusitis with nasal polyps (n = 27) patients. RESULTS: Increased arginase-2 activities in chronic rhinosinusitis without nasal polyps patients were associated with significantly lower levels of nasal fractional exhaled nitric oxide. Chronic rhinosinusitis with nasal polyps patients showed significant NOS2 messenger RNA upregulation with concomitant higher levels of oral and nasal fractional exhaled nitric oxide. CONCLUSION: These results indicate that fractional exhaled nitric oxide is a valid marker for differentiating chronic rhinosinusitis phenotypes based on a delicate balance between arginase and nitric oxide synthase activities in nitric oxide production.

Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study.

BACKGROUND: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. METHODS: This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. RESULTS: We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. CONCLUSION: We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.

Is the prognostic impact of tumor location in patients with surgically resected esophageal squamous cell carcinoma affected by surgical approach?

AIM: The aim of the present study was to clarify differences in node metastasis mode and clinical outcomes based on tumor location in patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Participants comprised 228 patients with ESCC who underwent radical esophagectomy without preoperative supplement therapies. Lymph nodes were harvested from three fields: the neck, thorax, and abdomen. Patients were divided into three groups depending on tumor location [upper esophagus (UE), middle esophagus, or lower esophagus (LE)] and analyzed clinicopathologically. RESULTS: The LE group showed significantly more progressive ESCC in terms of tumor invasion (p = 0.025), node metastasis (p = 0.0071), and TNM stage (p = 0.0043). The LE group revealed a tendency to metastasize to extrathoracic (especially abdominal) nodes (p = 0.0008). Recurrent laryngeal node metastasis was increased in the UE group (p = 0.016). However, no prognostic differences were detected between groups according to tumor location. Likewise, subgroup analyses by surgical approach (open thoracotomy vs. thoracoscopy) and cancer stage (stage I/II, III, and IV) did not reveal any significant prognostic impact of tumor location. CONCLUSION: Lymphatic spread varied by tumor location, but no prognostic impact of tumor location could be detected in patients with ESCC in spite of surgical approach or cancer stage.

A complex chromosome rearrangement involving four chromosomes, nine breakpoints and a cryptic 0.6-Mb deletion in a boy with cerebellar hypoplasia and defects in skull ossification.

Constitutional complex chromosomal rearrangements (CCRs) are considered rare cytogenetic events. Most apparently balanced CCRs are de novo and are usually found in patients with abnormal phenotypes. High-resolution techniques are unveiling genomic imbalances in a great percentage of these cases. In this paper, we report a patient with growth and developmental delay, dysmorphic features, nervous system anomalies (pachygyria, hypoplasia of the corpus callosum and cerebellum), a marked reduction in the ossification of the cranial vault, skull base sclerosis, and cardiopathy who presents a CCR with 9 breakpoints involving 4 chromosomes (3, 6, 8 and 14) and a 0.6-Mb deletion in 14q24.1. Although the only genomic imbalance revealed by the array technique was a deletion, the clinical phenotype of the patient most likely cannot be attributed exclusively to haploinsufficiency. Other events must also be considered, including the disruption of critical genes and position effects. A combination of several different investigative approaches (G-banding, FISH with different probes and SNP array techniques) was required to describe this CCR in full, suggesting that CCRs may be more frequent than initially thought. Additionally, we propose that a chain chromosome breakage mechanism may have occurred as a single rearrangement event resulting in this CCR. This study demonstrates the importance of applying different cytogenetic and molecular techniques to detect subtle rearrangements and to delineate the rearrangements at a more accurate level, providing a better understanding of the mechanisms involved in CCR formation and a better correlation with phenotype.

First report of a small supernumerary der(8;14) marker chromosome.

Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes, generally equal in size or smaller than a chromosome 20 of the same metaphase spread. Most of them are unexpectedly detected in routine karyotype analyses, and it is usually not easy to correlate them with a specific clinical picture. A small group of sSMCs is derived from more than one chromosome, called complex sSMCs. Here, we report on a patient with a de novo complex sSMC, derived from chromosomes 8 and 14. Banding karyotype analysis, multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism (SNP)-based array, and fluorescence in situ hybridization (FISH) were performed to investigate its origin. Array and FISH analyses revealed a der(14)t(8;14)(p23.2;q22.1)dn. The propositus presents some clinical features commonly found in patients with partial duplication or triplication of 8p and 14q. This is the first report describing a patient with a congenital der(14)t(8;14)(p23.2;q22.1)dn sSMC.

Interstitial 4q Deletion and Isodicentric Y-Chromosome in a Patient with Dysmorphic Features.

We present a 2-year-old boy with a de novo 46,XY,idic(Y)(q11.221),del(4)(q26q31.1) karyotype. G-banding, FISH, MLPA, and SNP-array techniques were used to characterize the 24-Mb deletion in 4q and the breakpoint in the isodicentric Y-chromosome region between 15,982,252 and 15,989,842 bp. The patient presented with mild facial dysmorphism, hemangioma, mild frontal cerebral atrophy, and Dandy-Walker variant. Essentially, this case reveals that patients can present more complex genomic imbalances than initially suspected.

Different conformation of two supernumerary 18p isochromosomes, one with a concomitant partial 18q trisomy.

The presence of a supernumerary 18p isochromosome is a rare chromosomal abnormality that results in 18p tetrasomy. This is a report on the clinical, cytogenetic and molecular findings of 2 non-related patients with a supernumerary 18p isochromosome. Both patients present some features of the 18p tetrasomy syndrome (strabismus, low-set ears, long and narrow fingers and toes), but additional characteristics were also observed. Cytogenetic analysis, FISH, MLPA and SNP array techniques showed that one of the isochromosomes is symmetric and monocentric, while the other is asymmetric and dicentric, yet resulting in a similar tetrasomy of the 18pter-18p10 region, followed by a partial 18q11.2 trisomy, an unprecedented finding in the literature.

Clinical, cytogenetic and molecular study in a case of r(3) with 3p deletion and review of the literature.

Ring chromosome 3 is a rare abnormality with only 10 patients described in the literature. We report a patient with r(3) and ∼6-Mb distal 3p deletion. Single nucleotide polymorphism array, multiplex ligation-dependent probe amplification and fluorescence in situ hybridization techniques revealed that the ring was formed by a break in 3p26.1 and fusion with the subtelomeric region of 3q. The patient presents delayed psychomotor development, growth failure, minor anomalies and other features similar to patients with 3p monosomy. The analysis of 300 metaphase cells using G-banding and fluorescence in situ hybridization with centromeric probe revealed ring instability resulting in cells with secondary aberrations and with ring loss that could also be related to some phenotypic characteristics such as growth delay. This is the first patient with r(3) studied using molecular techniques that determined the exact breakpoints in order to establish a better karyotype-phenotype correlation.

Hypermethylation of p16 gene promoter correlates with loss of p16 expression that results in poorer prognosis in esophageal squamous cell carcinomas.

The purpose of this study was to analyze loss of p16 expression and its relationship to hypermethylation, clinicopathological parameters and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Tissue samples from 60 ESCC were subjected to histological analysis. Immunohistochemical staining for p16 expression was performed. DNA was extracted from these primary esophageal tumors and from sera from another 38 ESCC patients. The DNA was modified with bisulfite and analyzed for p16 promoter methylation by methylation-specific polymerase chain reaction. Twelve out of the 60 tumors (20%) were methylated at the p16 promoter and 48 tumors (80%) were unmethylated. There were no significant correlations between the methylation of the p16 promoter and clinicopathological parameters. Immunohistochemical staining revealed that 41 of the 60 tumors (68.3%) were p16-negative and 19 tumors (31.7%) were p16-positive. The correlation between negative p16 immunohistochemical staining and methylation was statistically significant (P = 0.0084). No instances of p16 methylation and p16 positive immunostaining were found. There was a close correlation between loss of p16 expression and poorer prognosis in ESCC (P = 0.0517 in overall survival, P = 0.0478 in disease-free survival). The p16 gene promoter hypermethylation was detected in the serum of two of 38 (5.2%) patients with ESCC. This indicates that p16 promoter methylation suppresses p16 expression and that the loss of expression has a close relationship with poor prognosis in patients with ESCC. The present results may lead to the development of new therapeutic strategies, such as p16(INK4A) gene therapy, to treat patients with ESCC.

Aneuploidy of chromosome 8 detected by fluorescence in situ hybridisation in ACP01 cell line gastric adenocarcinoma.

Gastric cancer is the third most frequent type of neoplasia and the second most important cause of death in the world. ACP01 is the first gastric adenocarcinoma cell line developed in Brazil. To evaluate chromosomal aberrations implicated in gastric carcinogenesis, we analysed three different passages (6th, 12th and 35th) of ACP01 cell line by fluorescence in situ hybridisation using chromosome 8 alpha-satellite probe. Most of the chromosome 8 alterations found involved a numerical increase of this chromosome. Chromosome 8 trisomy was detected in all cases, varying from 37% (6th passage) to 67% (35th passage), and chromosome 8 tetrasomy (also observed in all passages) varied from 2.5% (6th passage) to 30% (35th passage). The presence of five signals for chromosome 8 was observed in all passages with the highest frequency found in the 12th passage (20%). Our results confirm that trisomy of chromosome 8 is a common biological phenomenon in adenocarcinoma of stomach and can be used as a gastric mucosa malignancy marker. Although gastric tumours are frequent neoplasias, papers on their cytogenetics are scarce in the literature. It is, therefore, necessary to conduct new studies aiming to identify peculiar genetic characteristics of a tumour, which might help in diagnosis and prognosis of this disease, besides allowing more accurate therapeutic conduct to be established.

Early and late gastric cancer arising in the remnant stomach after distal gastrectomy.

AIM: Following distal gastrectomy, carcinogenesis has been suggested to result from gastroduodenal reflux. In this study, surgical cases of gastric cancer arising after distal gastrectomy were analyzed clinico-pathologically and the possible link to reflux examined. PATIENTS: Thirty-two patients (24 males, 8 females; mean age, 68.7 years; age range, 33-84 years) with gastric cancer arising in the remnant stomach after gastrectomy (also known as gastric stump cancer) were included in this study. Patients were divided into two groups on the basis of the initial diagnosis (benign or malignant) prompting surgery, and distal gastrectomy reconstruction method (Billroth I or II). RESULTS: The interval between distal gastrectomy and detection of cancer in the remnant stomach of patients treated initially for a benign gastric condition vs. malignancy was 360+/-33.04 and 63+/-19.16 months (median+/-SE), respectively (p<0.0001). However, the benign and malignant groups did not differ significantly in the clinicopathological analysis of their stump cancers. All 10 patients in whom gastric cancer was diagnosed within five years of initial surgery had initially been surgically treated for malignancy. The interval between surgery and detection of gastric cancer in the Billroth I and Billroth II groups was 84+/-26.67 and 276+/-44.26 months (median+/-SE), respectively (p<0.01). In the remnant stomach, cancer tended to occur near the site of gastrojejunostomy in the Billroth II group (p=0.05). Helicobacter pylori infection was only detected histologically in four patients who had undergone Billroth I reconstructions after distal gastrectomy for malignancy. CONCLUSION: After distal gastrectomy, careful periodic endoscopic examination for microcarcinoma is required in patients, particularly in those who undergo surgery for malignancy, to maximize detection of gastric cancer.

Primary extramedullary plasmacytoma of the small intestine. A case report and review of the literature.

A case of primary extramedullary plasmacytoma of the small intestine in a 73-year-old Japanese woman was reported. The patient underwent local resection of the tumor, and showed no signs of local recurrence or dissemination of the disease after 28 months follow-up. The tumor cells had relatively large nuclei with distinct nucleoli and wide and slightly basophilic cytoplasm with a high N/C ratio which showed the morphology of atypical plasma cells. Immunohistochemical examination revealed that the tumor cells contained IgG gamma-type immunoglobulin in their cytoplasm but they did not contain IgA, IgM, IgD, and kappa-light chains. The tumor cells were also positive for CD79a and CD138 and negative for LCA, CD20 and CD45RO. These findings clearly indicated this case to be plasmacytoma.

Duplication 4p and deletion 4p (Wolf-Hirschhorn syndrome) due to complementary gametes from a 3:1 segregation of a maternal balanced t(4;13)(p16;q11) translocation.

We present clinical and cytogenetic data on a family with a t(4;13)(p16;q11) translocation present in four generations. The balanced translocation resulted in one individual with monosomy 4p and one individual with trisomy 4p, due to 3:1 segregation. The male patient with trisomy 4p was fertile and transmitted the extra chromosome to his daughter.

Two-step three-field lymph node dissection is beneficial for thoracic esophageal carcinoma.

Aggressive surgery including extensive lymph node dissection is considered necessary to improve the long-term survival of patients with esophageal carcinoma. While three-field lymph node dissection is widely performed for patients with thoracic esophageal carcinoma, cervical lymph node metastasis is uncommon. In order to reduce surgical stress, we have developed a two-step three-field lymph node dissection procedure for thoracic esophageal carcinoma. In the first-step operation, total thoracic esophagectomy through a right thoracotomy is performed. Mediastinal and abdominal lymph node dissection is performed synchronously. When recurrent nerve lymph node metastasis is pathologically positive, cervical lymph node dissection is performed about 3 weeks after the first operation (second step). Of 343 patients with carcinoma of the esophagus surgically treated in our department between 1990 and 2001, 146 underwent the operation described above. Three-field dissection was performed in 68 patients (group A), while two-field dissection was performed in 78 patients (group B). In the 68 group A patients, cervical lymph node metastasis was positive in 15 patients (22%). There was no marked difference in the onset of major complications between the two groups. The 5-year survival rate was 58% for group A and 61% for group B, not a statistically significant difference. In 78 of the 146 patients, it was possible to avoid cervical lymph node dissection without negatively affecting therapeutic outcomes. Two-step three-field lymph node dissection can reduce surgical stress of patients with good clinical outcome.

Rich example of geometrically induced nonlinearity: from rotobreathers and kinks to moving localized modes and resonant energy transfer.

We present an experimentally realizable, simple mechanical system with linear interactions whose geometric nature leads to nontrivial, nonlinear dynamical equations. The equations of motion are derived and their ground state structures are analyzed. Selective "static" features of the model are examined in the context of nonlinear waves including rotobreathers and kinklike solitary waves. We also explore "dynamic" features of the model concerning the resonant transfer of energy and the role of moving intrinsic localized modes in the process.

High level concentration of pyrimidine nucleoside phosphorylase in esophageal squamous cell carcinoma but no correlation with clinicopathological parameters.

Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine to 5'-fluorouracil, which exerts an anticancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). Recently, PyNPase has been shown to be identical to a potent angiogenic factor, platelet-derived endothelial cell growth factor. We analyzed the concentration of PyNPase and DPD in 33 patients with esophageal squamous cell carcinoma in fresh-frozen samples by enzyme-linked immunosorbent assay. In addition, we evaluated the clinical significance and prognostic value of PyNPase expression in esophageal carcinoma. The PyNPase concentration of tumor tissue was statistically higher than that of normal tissue of the esophagus (248 +/- 146 U/mg protein vs 73 +/- 63 U/mg protein, P = 0.0001), whereas DPD showed no difference (90 +/- 62 U/mg protein vs 88 +/- 62 U/mg protein, P = 0.825). The ratio of PyNPase to DPD of tumor tissue was statistically higher than that of normal tissue of the esophagus (3.3 vs 0.95, P = 0.0001). There were no significant differences between the group with high tumor to normal tissue ratios of PyNPase concentration and the low-ratio group in terms of the tumor length, depth, lymph node metastasis, lymph vessel invasion, vascular invasion, stage and survival. In conclusion, 5'-deoxy-5-fluorouridine may be effective on esophageal carcinoma and PyNPase concentration in esophageal carcinoma may not be a useful prognostic marker for patients with esophageal squamous cell carcinoma.