Squamous Neoplasia in the Esophagus.

CONTEXT.­: Squamous lesions of the esophagus encompass a spectrum of disorders ranging from reactive changes and benign papilloma to squamous dysplasia and squamous cell carcinoma, which may pose diagnostic challenges especially in superficial biopsies. OBJECTIVE.­: To provide a review on the typical features of squamous neoplasia in the esophagus, with an emphasis on the key diagnostic features as well as differential diagnosis from mimicking lesions. DATA SOURCES.­: Data sources include published peer-reviewed literature and personal experiences of the authors. CONCLUSIONS.­: Accurate diagnosis of squamous neoplasia requires adherence to established diagnostic criteria, attention to subtle histologic features, and correlation with clinical and imaging findings. In difficult cases, multiple biopsies may be necessary to reach a definitive diagnosis.

Common benign and malignant oral mucosal disease.

BACKGROUND: Mucosal diseases of the oral cavity are relatively common, and patients often seek initial assessment from their general practitioner. OBJECTIVE: The aim of this article is to provide an overview of common oral mucosal diseases to help with formulating a differential diagnosis and stratifying the urgency of referral. DISCUSSION: Pathological mucosal conditions of the oral cavity and jaws commonly present as a mucosal ulcer or a white, red or pigmented lesion. In this review, the authors outline the most common conditions organised according to their clinical presentation and describe their typical appearance and management.

Hydrochlorothiazide treatment and risk of non-melanoma skin cancer: Review of the literature. / Terapêutica com hidroclorotiazida e risco de cancro cutâneo não melanoma: revisão da literatura.

Non-melanoma skin cancer is the most prevalent malignancy in fair-skinned people and its incidence is increasing. Recently, studies have suggested that antihypertensive drugs may increase the risk of these tumors, particularly hydrochlorothiazide, due to its photosensitizing properties. The Portuguese National Authority for Medicines and Health Products, INFARMED, has issued an alert to healthcare professionals concerning the increased risk of non-melanoma skin cancer in patients exposed to cumulative doses of this drug. However, study results have been heterogeneous and sometimes conflicting. The high incidence of non-melanoma skin cancer and the large number of patients under chronic hydrochlorothiazide therapy may thus have important public health consequences. In this article, the authors review the published evidence and conclude that there may be an association between hydrochlorothiazide use and the risk of non-melanoma skin cancer, but also point out some limitations of the studies in the literature. It is important to promote preventive strategies against sun exposure, regular skin examinations, and individual assessment of the benefits of hydrochlorothiazide use, particularly in patients with previous skin cancer.

Lung Cancer in a Tertiary Hospital in Nepal: Clinical-Radiological Profile and Histological Subtypes.

BACKGROUND: Lung cancer is the most common cancer worldwide and in Nepal. Non small cell carcinoma is the commoner histological type. The incidence of adenocarcinoma subtype is increasing globally. This study aims to evaluate the clinical-radiological and histological profile and the diagnostic yield of various modalities in the diagnosis of lung cancer at a tertiary hospital in Nepal. METHODS: This is a prospective cross-sectional study conducted at National Academy of Medical Sciences, Kathmandu. Patients presenting with clinical and radiological features consistent with lung cancer and undergoing tissue sampling were included. The clinical and radiological characteristics, distribution of various histological subtypes and the diagnostic yield of various modalities were evaluated. RESULTS: Of the 253 patients screened, 77 meeting the inclusion criteria were enrolled into the study. Lung cancer was diagnosed in 53 patients. Forty (75.5%) patients had non small cell carcinoma and 13 (24.5%) had small cell carcinoma. Among the non small cell variants, 20 (37.7%) had adenocarcinoma and 19 (35.9%) had squamous cell carcinoma. Hitopathological diagnosis of lung cancer was established in 39 of the 42 (92.9%) patients by bronchoscopy. Image guided biopsy and/or aspiration yielded the diagnosis in 13 (24.5%) patients. The diagnostic yields of endobronchial biopsy, needle aspiration, bronchial brush and bronchial wash cytology were 86.5%, 70%, 63% and 34.3%respectively. CONCLUSIONS: The result of this study concurs with the global trend of rising incidence of adenocarcinoma subtype. Bronchoscopy remains the most commonly used tool for diagnosis of lung cancer and combination of procedures such as biopsy, bronchial brush, needle aspiration and bronchial wash provided the highest yield in our study.

Oral squamous papilloma: a view under clinical, fluorescence and histopathological aspects.

Oral squamous papilloma is a benign tumor whose pathogenesis has been associated with human papillomavirus infection. Thus, it is noteworthy that human papillomavirus infection is one of the risk factors associated with the development of cervical, anogenital, pharynx, larynx and oral cavity carcinomas. Oral squamous papilloma can affect any region of the oral cavity, and transmission of human papillomavirus can occur by direct contact, sexual intercourse or from mother to child during delivery. The diagnosis is clinical and histopathological, with surgical removal representing the treatment of choice. Recently, widefield optical fluorescence has been used as a complementary examination to the conventional clinical examination in the screening of oral pathological lesions and for the delimitation of surgical margins. We report a case of oral squamous papilloma with its clinical, histopathological features and, in addition, from the perspective of wide field optical fluorescence.

Retalho de peitoral maior estendido e pediculado para reconstrução de região orbito-fronto-parietal direita após exérese de carcinoma espinocelular invasivo / Extended and pedicled pectoralis major flap for right orbitofrontal-parietal reconstruction following invasive squamous cell carcinoma resection

Introdução: O retalho miocutâneo de peitoral maior é um dos mais usados na reconstrução de defeitos da cabeça e pescoço, porém com restrição ao terço médio da face. Com técnicas de dissecção de perfurantes, consegue-se alongar mais o pedículo, obtendo coberturas da região orbito-fronto-parietal. Relato de Caso: Paciente masculino de 63 anos apresentando carcinoma espinocelular invasivo pouco diferenciado, que após sua ressecção cirúrgica apresentou defeito final de 12,0 x 18,0cm na região órbito-fronto-parietal direita com exposição de dura-máter, seio frontal e órbita superior direita. Foi desenhado retalho de peitoral maior com ilha cutânea de dimensões iguais ao defeito na região paraesternal direita, desde o quarto espaço intercostal até a região subcostal (estendido). O pedículo foi seccionado após 4 semanas. A cobertura foi efetiva, sem complicações maiores e resultado estético satisfatório. Conclusão: Este retalho mostrou ser uma excelente opção para reconstrução do terço superior da cabeça quando existam limitações para a realização de microcirurgia.

Introdução: O retalho miocutâneo de peitoral maior é um dos mais usados na reconstrução de defeitos da cabeça e pescoço, porém com restrição ao terço médio da face. Com técnicas de dissecção de perfurantes, consegue-se alongar mais o pedículo, obtendo coberturas da região orbito-fronto-parietal. Relato de Caso: Paciente masculino de 63 anos apresentando carcinoma espinocelular invasivo pouco diferenciado, que após sua ressecção cirúrgica apresentou defeito final de 12,0 x 18,0cm na região órbito-fronto-parietal direita com exposição de dura-máter, seio frontal e órbita superior direita. Foi desenhado retalho de peitoral maior com ilha cutânea de dimensões iguais ao defeito na região paraesternal direita, desde o quarto espaço intercostal até a região subcostal (estendido). O pedículo foi seccionado após 4 semanas. A cobertura foi efetiva, sem complicações maiores e resultado estético satisfatório. Conclusão: Este retalho mostrou ser uma excelente opção para reconstrução do terço superior da cabeça quando existam limitações para a realização de microcirurgia.

Validation of a Clinical Cancer Register at the Head and Neck Oncology Center in Örebro.

BACKGROUND: This was a validation study of a regional register of oral cancer in Örebro, Sweden. The purpose was to assess the rate of errors in baseline, and treatment, and the completeness and accuracy of data on recurrences. MATERIALS AND METHODS: A total of 653 cases with squamous cell cancer in the oral cavity were identified from the register. A randomized sample of 73 (11%) was selected, and a set of relevant data was compared to medical records. RESULTS: Data on patient and tumour characteristics showed high accuracy, with 98% correct data and more than 99% of treatment data were correct. Follow-up data had a higher rate of errors, with 23% of recurrences not recorded, 13.6% misclassified, and 9.1% of cases showing errors in timing of the recurrence. CONCLUSION: data concerning patients, tumour status, and treatment in the Regional Head and Neck Register in Örebro are highly accurate. However, the follow-up data contain a higher rate of errors, that must be taken into consideration when evaluating outcome after treatment.

Oral squamous papilloma: a view under clinical, fluorescence and histopathological aspects / Papiloma escamoso oral: uma visão sob aspectos clínicos, de fluorescência e histopatológicos

ABSTRACT Oral squamous papilloma is a benign tumor whose pathogenesis has been associated with human papillomavirus infection. Thus, it is noteworthy that human papillomavirus infection is one of the risk factors associated with the development of cervical, anogenital, pharynx, larynx and oral cavity carcinomas. Oral squamous papilloma can affect any region of the oral cavity, and transmission of human papillomavirus can occur by direct contact, sexual intercourse or from mother to child during delivery. The diagnosis is clinical and histopathological, with surgical removal representing the treatment of choice. Recently, widefield optical fluorescence has been used as a complementary examination to the conventional clinical examination in the screening of oral pathological lesions and for the delimitation of surgical margins. We report a case of oral squamous papilloma with its clinical, histopathological features and, in addition, from the perspective of wide field optical fluorescence.

RESUMO O papiloma escamoso oral é um tumor benigno, cuja patogênese tem sido associada à infecção pelo papilomavírus humano. A infecção pelo papilomavírus humano é um dos fatores de risco associado ao desenvolvimento dos carcinomas cervicais, anogenitais, faríngeos, laríngeos e da cavidade oral. O papiloma escamoso oral pode acometer qualquer região da cavidade oral, e a transmissão do papilomavírus humano ocorre por contato direto, relação sexual ou de mãe para filho durante o parto. O diagnóstico é clínico e histopatológico, e a remoção cirúrgica representa o tratamento de escolha. Recentemente, a fluorescência óptica de campo amplo tem sido empregada como exame complementar ao exame clínico convencional, no rastreio de lesões patológicas orais e para delimitação de margens cirúrgicas. Relatamos um caso de papiloma escamoso oral com suas características clínicas e histopatológicas, sob a perspectiva da fluorescência óptica de campo amplo.

Circulating Heat Shock Protein 70 Is a Novel Biomarker for Early Diagnosis of Lung Cancer.

Heat shock protein 70 (HSP70) was a highly conserved protein which was significantly induced in response to cellular stresses. HSP70 played an important role in the pathogenesis of cancer which stabilized the production of large amount of oncogenic proteins and finally supported growth and survival of tumor. However, there was no report about the diagnosis of circulating HSP70 in lung cancer patients. In this study, a total of 297 participants (lung cancer: 197, healthy control: 100) were enrolled in the detection of circulating HSP70 level in plasma by ELISA assay. The results indicated that circulating HSP70 significantly decreased in lung cancer patients compared to healthy controls (P < 0.0001). Receiver operating characteristic (ROC) analysis showed that HSP70 (AUC: 82.2%, SN: 74.1%, SP: 80.0%) had higher diagnosis value than clinical existing biomarkers CEA (AUC: 80.1%, SN: 76.8%, SP: 67.3%) and CA 19-9 (AUC: 63.7%, SN: 64.2%, SP: 54.0%). In the analysis of early lung cancer patients, ROC results also revealed that HSP70 (AUC: 83.8%, SN: 71.2%, SP: 84.0%) have higher sensitivity, specificity, and AUC than CEA (AUC: 73.7%, SN: 73.2%, SP: 69.1%) and CA 19-9 (AUC: 61.5%, SN: 69.4%, SP: 53.4%). In analysis of specific histological classifications, HSP70 showed more valuable in the diagnosis of SCC (AUC: 85.9%, SN: 86.1.9%, SP: 81.0%) than ADC (AUC: 81.0%, SN: 69.1%, SP: 81.0%). Combined analysis of HSP70 and existing biomarker: CEA and CA 19-9 exhibited that HSP70 combined CEA and CA 19-9 showed the highest AUC (0.945, 95% CI, 0.855-1.000). The importance of our results was that we found decreased circulating HSP70, in combination with elevated CEA and CA 19-9, could be utilized in the diagnosis of early (stage I and II) lung cancer.

[Clinical analysis of 128 cases of cervical lesion diagnosed by multi-point biopsy of colposcopy and endocervical curettage].

Objective: To investigate the clinical values of colposcopy and cervical biopsy and/or endocervical curettage (ECC) in the diagnosis of cervical lesion. Methods: Clinical data of 128 cases of cervical lesion diagnosed by Xuzhou Cancer Hospital from January 23, 2014 to October 11, 2016 were collected and retrospectively analyzed, all patients underwent colposcopy and cervical biopsy and/or ECC. Results: Among them, the age between 30 to 50 years old were 70 cases, whose transformation zone types of Ⅰ, Ⅱ and Ⅲ were 28 cases (40.0%), 23 cases (32.9%) and 19 cases (27.1%), respectively. The age older than 50 years were 45 cases, whose transformation zone types of Ⅱ and Ⅲ were 1 case (2.2%) and 44 cases (97.8%), respectively. Among the 128 cases of cervical lesions, diagnostic results of colposcopy showed that the chronic inflammation were 57 cases, cervical intraepithelial neoplasia (CIN)Ⅰwere 35 cases, CINⅡor CINⅡ~Ⅲ were 8 cases, CIN Ⅲ were 5 cases and cervical cancer were 23 cases. Alternatively, the pathological results showed that the chronic inflammation were 81 cases, CINⅠwere 17 cases, CINⅡor CINⅡ~Ⅲ were 7 cases, CIN Ⅲ were 5 cases and cervical cancer were 18 cases, respectively. Among the 81 cases of chronic inflammation diagnosed by pathology, 52 cases (64.2%) were consistent with the diagnostic results of colposcopy. Among the 17 cases of low grade squamous epithelial cell lesion (LSIL) diagnosed by pathology, 10 cases were in agree with the diagnostic results of colposcopy. Among the 12 cases of high-grade squamous epithelial cell lesion (HSIL) diagnosed by pathology, 9 cases were concordant with the diagnostic results of colposcopy. Among the 18 cases of cervical cancer diagnosed by pathology, 17 cases were consistent with the diagnostic results of colposcopy. Conclusions: The type of transformation zone is positively correlated with the age, and it can help to choose biopsy and therapeutic manner. The diagnostic accuracies of HSIL and early stage of cervical cancer by multi-point biopsy of colposcopy and/or ECC are high. The cervical lesions which are difficultly found by direct visualization can be identified by colposcopy, and thus provides objective evidence to determine the therapeutic manner for patients with stage ⅡA of cervical cancer.

[Cervical cancer has increased in Sweden in women who had a normal cell sample]. / Livmoderhalscancer ökar hos kvinnor med normalt cellprov - Skillnader mellan laboratorier tyder på att ökningen orsakas av faktorer som kan åtgärdas.

Cervical cancer has increased in Sweden in recent years. The increase is 17% in 2014-15 compared to the reference period 2002-13. The increase is largest for adenocarcinoma (+ 31%) and shows remarkable differences between counties, from continued incidence decreases to increases of >80%. The increase is seen in most ages that are offered screening, but is confined to early stage cancers and there is no increase in mortality. Population test coverage of screening has increased since 2002. The Swedish National Cervical Screening Registry has analysed the increase in relation to screening history. The most significant increase (+ 30%) is seen in women who had a normal cervical smear (P < 0.0001) in the preceding screening interval. The cancer risk for women who previously had a high grade abnormality has also increased (P = 0.0009). Data from several laboratories still show very low cancer risk following normal cytology, indicating that the increase is related to factors that can be addressed. All data on re-review of samples taken before cancer and high grade intraepithelial neoplasia will be requested and nationally analyzed to further elucidate the exact cause.

Nivolumab-induced synchronous occurrence of myositis and hypothyroidism in a patient with squamous cell lung cancer.

AIM: Alongside the proven efficacy, immunotherapy in treatment of malignant diseases can cause immune-related adverse events different from commonly known chemotherapy-related toxicities. CASE PRESENTATION: During nivolumab treatment of metastatic squamous cell lung cancer, the patient developed a symptomatic inflammatory myositis confirmed with muscle biopsy and primary hypothyroidism. After initiation of corticosteroids and thyroid hormone replacement, the clinical and laboratory improvement occurred. To the best of our knowledge, this is the first description of a case of nivolumab-induced synchronous manifestation of immune-related myositis and hypothyroidism. CONCLUSION: Immunotherapy can trigger a wide spectrum of immune-related adverse events that could occur simultaneously. If not detected and treated, these events could become severe or even fatal and require clinicians' awareness and routine check-ups.

Fibroblast growth factor receptor 1 and 3 expression is associated with regulatory PI3K/AKT kinase activity, as well as invasion and prognosis, in human laryngeal cancer.

PURPOSE: Aberrant fibroblast growth factor receptor (FGFR) expression is thought to contribute to the development of many types of cancer. As yet, however, their impact on the course and prognosis of head and neck cancer remains to be determined. Here, we aimed to investigate the effects of expression of the FGFR family members FGFR1 and FGFR3, as well as their downstream PI3K/AKT signal-regulated kinases, on the aggressiveness and prognosis of laryngeal cancer. METHODS: In total 137 surgically removed squamous cell laryngeal cancer (SCLC) and 100 matched non-cancerous laryngeal mucosa (NCLM) samples were assessed for mRNA expression using quantitative real-time PCR. The corresponding proteins were analyzed by Western blotting. SLUG expression was assessed by immunohistochemistry. The expression data were subsequently related to tumor front grading (TFG), local/nodal recurrences, prognosis and overall survival. RESULTS: The FGFR1, FGFR3 and PI3K/AKT kinase mRNA and protein levels were found to be significantly higher in the SCLC than the NCLM samples (p < 0.05). A high FGFR1 mRNA/protein expression level was found to be associated with an increased invasion rate, according to TFG scale and SLUG level, a high local/nodal recurrence rate and a poor prognosis (p < 0.05). Similarly, we found that a high FGFR3 mRNA/protein expression level was associated with a shorter survival time (p < 0.05). In addition, we found that high PI3K/AKT kinase mRNA/protein levels were associated with a high TFG (p < 0.05). We also found that FGFR1/3 mRNA and FGFR1 protein levels were inversely associated with overall survival (log-rank test: FGFR1 mRNA p = 0.03, FGFR3 mRNA p = 0.04, FGFR1 protein p = 0.03). Subsequent multivariate analyses revealed that high FGFR3 mRNA expression may serve as an independent poor prognostic factor (HR 2.32, 95% CI 1.03-6.59; p = 0.04). We also found that the p-PI3K regulatory kinase protein level was significantly associated with survival in the cohort studied (HR 1.78, 95% CI 0.64-8.53; p = 0.03). CONCLUSIONS: From our data we conclude that FGFR1 and FGFR3, as well as its downstream regulatory PI3K/AKT kinases, may serve as potential biomarkers for the invasiveness and prognosis of laryngeal cancer. The expression of FGFR1/3-PI3K/AKT regulatory pathway members may be instrumental for the identification of patients at risk for an unfavorable clinical outcome.

Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer.

BACKGROUND: Epigenetic alterations are strongly associated with the development of cancer. The aim of this study was to identify epigenetic pattern in squamous cell lung cancer (LUSC) on a genome-wide scale. RESULTS: Here we performed DNA methylation profiling on 24 LUSC and paired non-tumor lung (NTL) tissues by Illumina Human Methylation 450 K BeadArrays, and identified 5214 differentially methylated probes. By integrating DNA methylation and mRNA expression data, 449 aberrantly methylated genes accompanied with altered expression were identified. Ingenuity Pathway analysis highlighted these genes which were closely related to the carcinogenesis of LUSC, such as ERK family, NFKB signaling pathway, Hedgehog signaling pathway, providing new clues for understanding the molecular mechanisms of LUSC pathogenesis. To verify the results of high-throughput screening, we used 56 paired independent tissues for clinical validation by pyrosequencing. Subsequently, another 343 tumor tissues from the Cancer Genome Atlas (TCGA) database were utilized for further validation. Then, we identified a panel of DNA methylation biomarkers (CLDN1, TP63, TBX5, TCF21, ADHFE1 and HNF1B) in LUSC. Furthermore, we performed receiver operating characteristics (ROC) analysis to assess the performance of biomarkers individually, suggesting that they could be suitable as potential diagnostic biomarkers for LUSC. Moreover, hierarchical clustering analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation. CONCLUSIONS: Collectively, these results suggest that DNA methylation plays critical roles in lung tumorigenesis and may potentially be proposed as a diagnostic biomarker. TRIAL REGISTRATION: ChiCTR-RCC-12002830 Date of registration: 2012-12-17.

New Developments and Challenges in Rare Genitourinary Tumors: Non-Urothelial Bladder Cancers and Squamous Cell Cancers of the Penis.

The diagnosis and treatment of rare genitourinary tumors is inherently challenging. The Rare Diseases Act of 2002 initially defined a rare disorder as one that affects fewer than 200,000 Americans. The lack of widely available clinical guidelines, limited research funding, and inaccessible clinical trials often lead to difficulty with treatment decisions to guide practitioners in rendering effective care for patients with rare genitourinary cancers. This article will discuss basic tenets of diagnosis and treatment as well as recent developments and clinical trials in rare non-urothelial bladder cancers and penile squamous cell cancers.