Predictors of higher number of stages in Mohs micrographic surgery for the treatment of squamous cell carcinoma of the head

BACKGROUND - Squamous cell carcinomas of the skin of the bead are better treated with Mobs micrographic surgery which has the lowest recurrence rates and allows spare normal tissue. There are some characteristics of squamous cell carcinoma that can be related to a higher number of surgical stages. OBJECTIVE - To study characteristic of head squamous cell carcinoma that predicts a higher number of Mohs surgical stages. METHODS - A retrospective analysis of 51 squamous cell carcinomas of the bead treated with Mobs surgery was performed to determine risk factors for a higher number of surgical stages. The characteristics analyzed were clinical limits, morphology, recurrence, histological differentiation and size and compared to the number of surgical stages. The analysis was performed by Fisher`s exact test and multivariate logistic regression. RESULTS - The recurrent squamous cell carcinomas showed a tendency for a higher number of stages (p=0,081). The Odds Ratio for a higher number of Mobs stages was three for inaccurate limits; although not statistically significant, it corroborates clinical and previous publication. CONCLUSION - Clinical characteristics of squamous cell carcinoma as recurrence and inaccurate limits would not predict, but could indicate tendency of a higher number of Mobs micrographic surgery stages.

Barrett`s esophagus (BE) and carcinoma in the esophageal stump (ES) after esophagectomy with gastric pull-up in achalasia patients: A study based on 10 years follow-up

Background: Subtotal esophagectomy and gastric pull-up with cervical anastomosis is the main treatment for advanced achalasia. This surgical technique has been associated to esophagitis and also Barrett`s epithelium following esophagectomy. Aim: To analyze late clinical, endoscopic, and pathologic findings in the esophageal stump (ES) mucosa after subtotal esophagectomy in patients treated for advanced chagasic achalasia. Methods: 101 patients submitted to esophagectomy and cervical gastroplasty were followed-up prospectively for a mean of 10.5 +/- 8.8 years. All patients underwent clinical, endoscopic and histopathological evaluation every 2 years. Gastric acid secretion was also assessed. Results: The incidence of esophagitis in the esophageal stump (45.9% at 1 year; 71.9% at 5 years, and 70.0% at 10 years follow-up); gastritis in the transposed stomach (20.4% at 1 year, 31.0% at 5 years, and 40.0% at 10 or more years follow-up), and the occurrence of ectopic columnar metaplasia and Barrett`s Esophagus in the ES (none until 1 year; 10.9% between 1 and 5 years; 29.5% between 5 and 10 years; and 57.5% at 10 or more years follow-up), all rose over time. Gastric acid secretion returns to its preoperative values 4 years postoperatively. Esophageal stump cancer was detected in the setting of chronic esophagitis in five patients: three squamous cell carcinomas and two adenocarcinomas. Conclusion: (1) Esophagitis and Barrett`s esophagus in the esophageal stump rose over time. (2) These mucosal alterations and the development of squamous cell carcinoma and adenocarcinoma are probably due to exposure to duodenogastric reflux, and progressively higher acid output in the transposed stomach.

Acinar cell carcinoma of the pancreas: is the absence of neuroendocrine component related to a more malignant behavior?

Background/Aims: Acinar cell carcinomas are uncommon malignant tumors of the pancreas, accounting for 1-2% of all the cases of exocrine pancreatic tumor. Some authors have estimated acinar cell tumors to be as aggressive as ductal adenocarcinoma of the pancreas whereas other series showed acinar cell tumors to have a favorable clinical outcome. This discrepancy in prognosis may be related to the cellular components of the tumor. Methodology: With the aim to evaluate the possible relationship between the presence of neuroendocrine differentiation and behavior of these tumors, the authors reviewed all patients presenting acinar cell carcinoma of the pancreas in the last 5 years with emphasis in the immunohistochemical evaluation. Results: Four patients presented neuroendocrine differentiation on immunohistochemical evaluation and had a more benign outcome. Two patients without neuroendocrine component had a disseminated disease at presentation. This data suggests that this tumor is less aggressive than ductal adenocarcinoma and even with nodal involvement, long term survival after complete resection can be achieved. Conclusions: It is possible that the absence of neuroendocrine component may be related to a less favorable outcome and adjuvant therapy may be necessary. Due to the rarity of this pancreatic tumor, this relationship remains to be confirmed with a multicentric study including a larger number of patients.

CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients

Head and neck squamous cell carcinoma (HNSCC) is associated with environmental factors, especially tobacco and alcohol consumption. Most of the carcinogens present in tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYPs) enzymes and detoxification of these substances is performed by glutathione S-transferases (GSTs). It has been suggested that genetic alterations, such as polymorphisms, play an important role in tumorigenesis and HNSCC progression. The aim of this study was to investigate CYP1A1, CYP1A2, CYP2E1, GSTM1, and GSTT1 polymorphisms as risk factors in HNSCC and their association with clinicopathologic data. The patients comprised 153 individuals with HNSCC (cases) and 145 with no current or previous diagnosis of cancer (controls). Genotyping of the single nucleotide polymorphisms (SNPs) of the CYP1A1, CYP1A2, and CYP2E1 genes was performed by PCR-RFLP and the GSTM1 and GSTT1 copy number polymorphisms (CNPs) were analyzed by PCR-multiplex. As expected, a significant difference was detected for tobacco and alcohol consumption between cases and controls (P < 0.001). It was observed that the CYP1A2*1D (OR = 16.24) variant and GSTM1 null alleles (OR = 0.02) confer increased risk of HNSCC development (P < 0.001). In addition, head and neck cancer alcohol consumers were more frequently associated with the CYP2E1*5B variant allele than control alcohol users (P < 0.0001, OR = 190.6). The CYP1A2*1C polymorphism was associated with tumor recurrence (log-rank test, P = 0.0161). The CYP2E1*5B and GSTM1 null alleles were significantly associated with advanced clinical stages (T3 + T4; P = 0.022 and P = 0.028, respectively). Overall, the findings suggested that the genetic polymorphisms studied are predictors of risk and are also associated with tumor recurrence, since they are important for determining the parameters associated with tumor progression and poor outcomes in HNSCC. (C) 2009 Elsevier Ltd. All rights reserved.

Extremely late development of pituitary carcinoma after surgery and radiotherapy

Introduction Pituitary carcinomas account for 0.1 or 0.2% of pituitary tumors. The authors report a rare case of a pituitary carcinoma mimicking a radio-induced meningioma. Case report Fifty-five years-old male presents a previous history of transcranial surgery in 1983 for invasive pituitary adenoma followed by whole-brain radiotherapy (5100 cGy). After three years he presented worsening of visual deficits and MRI evidenced recurrence of the lesion. In 1992, he underwent a transcranial approach to treat recurrent supraselar disease, followed by stereoctatic radiotherapy. In 2006, clinical condition was stable; however three right frontal extra-axial lesions were diagnosed by MRI, compatible with meningioma. The histological examination revealed pituitary adenoma. No lesions were found in craniospinal axis. Further treatment was not recommended by radiotherapists due previous actinic treatments. Two years radiological follow-up revealed no recurrence. Conclusion In these high risk cases, active and constant surveillance must be pertained, regardless the time of follow-up.

Evaluation of inverted papilloma and squamous cell carcinoma by nasal contact endoscopy

Background: Contact endoscopy (CE) was initially described as a method used in the analysis of uterine and vocal folds histology. The first nasal cavity CE studies achieved promising results regarding its use for the differentiation between benign and malignant lesions, considering that biopsy might cause some complications, especially bleeding. This study described and compared the findings of CE on inverted papilloma and nasosinusal squamous cell carcinoma (SCC) and tested the effectiveness of this exam as a noninvasive method for in vivo differentiation between these tumors. Methods: The patients included in this study were divided into group A, patients diagnosed with inverted papilloma, and group B, patients diagnosed with SCC. CE results were compared among themselves. CE images were presented to examiners not experienced with the method. Results: Twenty-two patients were examined, 13 in group A and 9 in group B. The main relevant differences in CE findings between those two groups were corkscrew vessels, presence of mitoses, keratinization and nuclear pleomorphism in carcinoma, and vacuolated cells in papilloma. The examiners were capable of defining the diagnosis of these nasal tumors only based on CE images. Conclusion: CE may be a useful noninvasive exam to be used in the in vivo diagnosis of inverted papilloma and nasosinusal SCC, which may enable better preoperative planning. (Am J Rhinol Allergy 24, 210-214, 2010; doi: 10.2500/ajra.2010.24.3467)

Imiquimod 5% Cream for the Treatment of Periocular Basal Cell Carcinoma

Purpose: The objective of this pilot study was to evaluate the efficacy and safety of 5% imiquimod cream in the treatment of periocular basal cell carcinoma (BCC) through the analysis of a case series. Methods: Eight subjects with primary nodular BCC of the eyelid were recruited. Treatment lasted 10 to 16 weeks. The average follow-up time was 11.7 months. Results: Of a total of 10 lesions, 80% resolved clinically and histologically and have remained asymptomatic since. Conclusion: Imiquimod cream 5% was shown to be an attractive alternative to surgical treatment of periocular BCC. Future studies with larger samples and longer follow-up periods are expected to provide more accurate information on the efficacy and safety of the drug.

Claudin and p53 expression in vulvar lichen sclerosus and squamous-cell carcinoma

Aims Vulvar squamous-cell carcinoma (SCC) is a rare gynaecological cancer. Vulvar SCC has been shown to develop from vulvar intraepithelial neoplasias, which are related to lichen sclerosus (LS). Most studies to date have compared vulvar SCC with LS only morphologically, but no detailed molecular analysis has been performed. The objective was to compare claudin and p53 expression in these diseases and determine if there was any association with expression and vulvar SCC progression. Methods Immunohistochemical analysis was performed in order to determine expression of p53 and claudin 1, 2, 3, 4, 5, 7 and 11 in human vulvar tissue samples from LS, SCC and control patients. Results Claudin 1, 2, 3, 4 and 5 were expressed comparably in the three groups. Claudin 7 and 11 expression was significantly decreased in LS and SCC samples compared with the control group. Expression of p53 was significantly increased in SCC and LS patient samples compared with the control group. Conclusions Claudin 7 and 11 were not expressed in LS and SCC. However, there was no significant difference in expression of any of the claudins between the LS and SCC samples. Furthermore, p53 expression is the highest in SCC patients and lowest in the control group. However, expression of p53 did not vary between samples from isolated LS and LS associated SCC patients, suggesting that increased p53 expression is not the determining factor in the progression of LS lesions to SCC.

Hematological indices at birth in relation to arterial and venous Doppler in small-for-gestational-age fetuses

Objective. To correlate Doppler results with hematological indices at birth in small-for-gestational-age (SGA) fetuses. Design. Prospective study. Setting. Tertiary teaching hospital, Sao Paulo, Brazil. Population. One hundred singleton pregnancies with SGA fetuses of > 27 weeks gestational age. Methods. All women had Doppler velocimetry of the umbilical arteries, middle cerebral artery, and ductus venosus within < 72 hours prior to delivery. After birth, umbilical artery blood was collected for hematological analysis. Main outcome measures. The association between fetal Doppler velocimetry pulsatility index (PI) and some hematological indices. Results. Umbilical artery PI showed a positive correlation with nucleated red blood cell count in the umbilical cord (r = 0.46; p<0.01), and a negative correlation with platelet count (r = -0.53; p<0.01) and white blood cell count (r = -0.42; p<0.01). Middle cerebral artery PI was positively correlated with platelet count (r = 0.43; p<0.01) and white blood cell count (r = 0.38; p<0.01), and was negatively correlated with nucleated red blood cell count (r = -0.39; p<0.01). The ductus venosus pulsatility index showed a positive correlation with nucleated red blood cell count (r = 0.36; p<0.01), and a negative correlation with platelet count (r = -0.37; p<0.01) and white blood cell count (r = -0.26; p<0.01). Conclusion. A significant positive or negative correlation between nucleated red blood cell, platelet and white blood cell counts, and Doppler indices suggests an association between placental insufficiency and the fetal hematological response.

Marijuana Smoking and the Risk of Head and Neck Cancer: Pooled Analysis in the INHANCE Consortium

Background: Marijuana contains carcinogens similar to tobacco smoke and has been suggested by relatively small studies to increase the risk of head and neck cancer (HNC). Because tobacco is a major risk factor for HNC, large studies with substantial numbers of never tobacco users could help to clarify whether marijuana smoking is independently associated with HNC risk. Methods: We pooled self-reported interview data on marijuana smoking and known HNC risk factors on 4,029 HNC cases and 5,015 controls from five case-control studies within the INHANCE Consortium. Subanalyses were conducted among never tobacco users (493 cases and 1,813 controls) and among individuals who did not consume alcohol or smoke tobacco (237 cases and 887 controls). Results: The risk of HNC was not elevated by ever marijuana smoking [odds ratio (OR), 0.88; 95% confidence intervals (95% Cl), 0.67-1.16], and there was no increasing risk associated with increasing frequency, duration, or cumulative consumption of marijuana smoking. An increased risk of HNC associated with marijuana use was not detected among never tobacco users (OR, 0.93; 95% Cl, 0.63-1.37; three studies) nor among individuals who did not drink alcohol and smoke tobacco (OR, 1.06; 95% Cl, 0.47-2.38; two studies). Conclusion: Our results are consistent with the notion that infrequent marijuana smoking does not confer a risk of these malignancies. Nonetheless, because the prevalence of frequent marijuana smoking was low in most of the contributing studies, we could not rule out a moderately increased risk, particularly among subgroups without exposure to tobacco and alcohol. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1544-51)

The outer wall of small airways is a major site of remodeling in fatal asthma

Background: Structural and inflammatory changes in asthma involve both the large and small airways, with involvement of the distal lung being related to disease severity. We have previously shown that changes in the extracellular matrix (ECM) composition of the distal lung are associated with loss of alveolar attachments in patients with fatal asthma. However, major ECM elements, such as collagen I and fibronectin and their regulators, have not been addressed at the distal level. Objective: We sought to evaluate ECM remodeling in the distal lungs of asthmatic patients. Methods: Using immunohistochemistry and image analysis, we determined the content of collagen I and III, fibronectin, and matrix metalloproteinases; (MMPs) 1, 2, and 9 and tissue inhibitors of metalloproteinase (MMPs) 1 and 2 in the large and small airways and lung parenchyma of 24 patients with fatal asthma and compared the results with those of 11 nonasthmatic control subjects. Protein content was defined as the area of positive staining divided by basement membrane or septum length. Results: We observed increased collagen I and decreased collagen III content in the small airways of asthmatic patients compared with that seen in control subjects. Greater fibronectin and MMP-1, MMP-2, and MMP-9 content was observed at the outer area of the small airways in asthmatic patients. NIMP content was also increased in the peribronchiolar parenchyma in asthmatic patients. In contrast, TIMP expression was only increased in the large airways of asthmatic patients compared with that seen in control subjects. Conclusions: The outer area of the small airways is a major site of ECM remodeling in fatal asthma, potentially contributing to functional changes and the loss of airway-parenchyma interdependence observed in patients with fatal asthma. (J Allergy Clin Immunol 2009;123:1090-7.)

Prognostic relevance of TTF-1 and MMP-9 expression in advanced lung adenocarcinoma

Background: The thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor that Could playan important role in cell differentiation and morphogenesis of lung tumors. Matrix metalloproteinase-9 (MMP-9) is a protease commonly expressed in non-small cell lung cancer, conferring angiogenic and metastatic potential. Methods: We assessed TTF-1 and MMP-9 tumor expression by immunohistochemistry in 51 patients with lung adenocarcinoma, stage 11113 or IV, treated with platinum regimens. A bicategorical prognostic model was obtained using the Kaplan-Meier method, COX regression, and conjunctive consolidation. Results: The median expression of TTF-1 was 30.0% (range: 0-85.9%). All tumors expressed MMP-9 (median: 78.7%: range: 15.2-96.1%). Median survival was 41.6 weeks, with estimated 1- and 2-year survival rates of 45.0% and 22.0%, respectively. Poor performance status (Karnofsky scale) - hazards ratio(HR): 1.03. 95% confidence interval (CI): 1.01-1.06: low TTF-1 expression (<40%) - FIR: 4.00, 95% CI: 1.75-9.09: and high MMP-9 expression (>= 80%) - HR: 2.82, 95% CI: 1.30-6.08 were independent prognostic factors. Patients could be stratified in three death risk groups according to markers expression: low risk (high TTF-1 and low MMP-9; median survival: 127.6 weeks), intermediate risk (low TTF-1 OF high MMP-9; median survival: 39.0 weeks): and high risk (low TTF-1 and high MMP-9: median survival: 16.4 weeks). Conclusion: TTF-1 and MMP-9 tumor expression as detected by immunohistochemistry may allow identification of different, clinically meaningful, prognostic groups of advanced lung adenocarcinoma patients treated with platinum regimens. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Annexin A1 subcellular expression in laryngeal squamous cell carcinoma

Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.

Immunophenotyping and remodeling process in small airways of idiopathic interstitial pneumonias: functional and prognostic significance

Background and Aims: To test whether different degrees of immunologic and fibrotic airway remodeling processes occur in idiopathic interstitial pneumonias (IIPs), with impact on functional tests and survival, we studied the collagen/elastic system and immune cell density in the bronchiolar interstitium of lungs with the major types of IIPs. Materials and Methods: Histochemistry, immunohistochemistry and morphometric analysis were used to evaluate collagen/elastic fibers and immune cells in the bronchiolar interstitium of open lung biopsies of patients with cryptogenic organizing pneumonia [COP/organizing pneumonia (OP) = 10], acute interstitial pneumonia [AIP/diffuse alveolar damage (DAD) = 20], nonspecific interstitial pneumonia (NSIP/NSIP = 20) and idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP) = 20. Results: OP lungs presented a significant increase in collagenous/elastic fibers and in the total density of immune cells in the bronchiolar interstitium compared to controls, DAD, NSIP and UIP. We observed a significant increase in CD4, CD8 and CD20 lymphocytes, as well as in neutrophils, macrophages and plasma cells in OP. The increased amount of elastic fibers in the bronchiolar interstitium from OP lungs has a direct association with forced vital capacity (FVC) (r(s) = 0.99, P = 0.03). The most important survival predictor was CD20+ lymphocytes in the bronchiolar interstitium. In decreasing order, patients with UIP [Odds Ratio (OR) = 35.01], high forced expiratory volume in 1 s (FEV1)/FVC FVC (OR = 7.01), increased CD20+ lymphocytes (OR = 4.44) and collagenous/elastic fiber densities (OR = 2.03 and OR = 1.49, respectively) in the bronchiolar interstitium were those who had the greatest risk of death, followed by those with AIP, NSIP and COP. Conclusion: Different degrees of immunologic and fibroelastotic airway remodeling processes occur in the major types of IIPs with impact on physiological tests and survival.

Peritumoural, but not intratumoural, lymphatic vessel density and invasion correlate with colorectal carcinoma poor-outcome markers

To evaluate whether lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) are useful markers of worse outcome in colorectal carcinoma and if LVD and LVI correlate to the classical clinical-pathological parameters, we analysed 120 cases of colorectal carcinomas selected from the files of Division of Pathology, Hospital das Clinicas, Sao Paulo University, Brazil. Assessment of LVD and LVI was performed by immunohistochemical detection of lymphatic vessels, using the monoclonal antibody D2-40. Higher LVD was found in the intratumoural area, when comparing with normal and peritumoural areas (p < 0.001). However, peritumoural LVD, but not intratumoural, correlated with both colonic-wall-invasion depth (p=0.037) and liver metastasis (p=0.012). Remarkably, LVI was found associated with local invasion (p=0.016), nodal metastasis (p=0.022) and hepatic metastasis (p < 0.001). Peritumoural LVD and LVI are directly related to histopathological variables indicative of poor outcome such as lymph-node status and liver metastasis.