Primary Neoplasia Research Articles

Retrospective evaluation of canine primary, multicentric, and metastatic intraocular neoplasia.

To provide an updated characterization of the prevalence of primary, multicentric, and metastatic intraocular tumors in the canine patient. Medical records databases from 4 veterinary referral hospitals were reviewed from 1999 to present to identify dogs with a diagnosis of intraocular neoplasia histopathologically confirmed following enucleation or necropsy. One hundred seventy-two dogs with 173 intraocular neoplasms met the inclusion criteria. Primary intraocular neoplasms were the most common tumors in the study (128); the two most common types were melanocytic neoplasia (90), followed by iridociliary neoplasia (33). There were 28 cases of intraocular involvement secondary to round cell neoplasia, with 18 cases of lymphoma, seven histiocytic sarcomas, and three undifferentiated round cell neoplasms. There were 17 cases of metastatic intraocular neoplasia, with hemangiosarcoma being the most common (9). The majority of intraocular tumors in dogs arise from the ocular tissues. However, the eye may also be involved in patients with multicentric neoplasia, and, less commonly, as a site for metastatic disease. Ocular screening for patients with multicentric neoplasia should be considered during staging, and ocular signs should be viewed with suspicion in dogs with neoplasia in other sites.

Feline pancytopenia: a review of causes, investigation and treatment

Pancytopenia refers to a decrease in circulating levels of erythrocytes, neutrophils and platelets. These changes typically occur as a result of reduced production within the bone marrow or from peripheral cell destruction. A variety of causes have been reported in the literature, including primary bone marrow disorders, neoplasia, infectious diseases and toxins. When presented with a case of feline pancytopenia, it is important to take a thorough history, including travel history and any recent husbandry changes. Treatment and prognosis are dependent on the underlying cause, with favourable outcomes more commonly reported in cases of toxicity and certain infectious diseases. This article summarises the reported causes of pancytopenia, and provides a structured approach to managing these cases in practice.

Epidemiological, clinical and therapeutic characteristics of metastatic spinal cord compression in prostate cancer patients in two tertiary hospitals in Cameroon

Introductionprostate cancer represents the 3rd primary neoplasia responsible for metastatic spinal cord compression (MSCC). MSCC is an extreme oncological emergency, because it involves both functional and vital prognosis. The present study aimed to establish a pattern of MSCC in prostate cancer patients in Douala and Yaoundé general hospitals (Cameroon).Methodsthis was a descriptive and retrospective study in the Radiotherapy and Medical Oncology services at both Douala and Yaoundé General Hospitals. The explored variables were general characteristics of the study population, clinical and paraclinical features, management and outcomes. Furthermore 5-year survival was analyzed by the Kaplan-Meier method. Logistic regression by determining the odd ratios and their 95% confidence was done using “Statistical Package for Social Sciences” (SPSS 23) software. The difference was considered significant at p < 0.05.Resultsour series consisted of 151 patients out of which the mean age was 66.88 (SD: 8.71) years (95% CI: 44-88). Pain was the most common clinical symptom (53.33%; n= 80) and fracture-settlement accounted for majority (60%; n= 90.61) of the pain. Thoracic spine damage was encountered by 47.02% (n= 71). Patients received a total doses of irradiation between 20 and 30 gray (Gy). The main toxicity due to radiotherapy were asthenia (45.70%; n= 69.11). The overall survival at 5 years was 90.11%. Factors associated with fracture-settlement were smoking (aOR 10.04, 95% CI: 2.09-48.12; p = 0.004) and the localization of MSCC occurred (aOR 0.21, 95% CI: 0.05-0.77; p = 0.02).Conclusionin summary the average age for developing the condition is 66.88 years and factors associated with fracture-settlement were smoking and the localization of MSCC. Back pain was the most common clinical sign and fracture-settlement was the first type of injury on medical magnetic resonance imaging. Therefore, we recommend that emphasis should be placed on increasing awareness of the population on the importance of early diagnosis.

Feline Uveal Melanoma Review: Our Current Understanding and Recent Research Advances.

Melanocytic neoplasia is the most common form of ocular tumour in cats, accounting for 67% of cases in an analysis of 2614 cases of primary ocular neoplasia. Feline diffuse iris melanoma (FDIM) is by far the most common form of ocular melanocytic neoplasia, with limbal melanomas and atypical melanoma (melanoma affecting the choroid or ciliary body) infrequently recognised. Early lesions begin as flat areas of pigmentation of the iris, known as iris melanosis. This melanosis is a precursor lesion that can become FDIM when pigmented cells infiltrate the anterior iris stroma, commonly alongside a transition in cell morphology. The differentiation between FDIM and benign iris melanosis is only recognisable though histologic examination, with no in vivo means of identifying the malignant transformation. The behaviour of FDIM is variable and difficult to predict. Some FDIM lesions have a more benign progression and can slowly grow or remain static for years without affecting the ocular or systemic health of the individual, whilst other tumours behave aggressively, invading the ocular structures and significantly affecting the life expectancy of cats through metastatic disease. This makes management and timely enucleation of these cases challenging in practice. This article aims to review our current knowledge of FDIM.

Distribution of histopathologic types of primary pulmonary neoplasia in dogs and outcome of affected dogs: 340 cases (2010–2019)

To provide updated information on the distribution of histopathologic types of primary pulmonary neoplasia in dogs and evaluate the effect of postoperative adjuvant chemotherapy in dogs with pulmonary carcinoma. 340 dogs. Medical records of dogs that underwent lung lobectomy for removal of a primary pulmonary mass were reviewed, and histopathologic type of lesions was determined. The canine lung carcinoma stage classification system was used to determine clinical stage for dogs with pulmonary carcinoma. Pulmonary carcinoma was the most frequently encountered tumor type (296/340 [87.1%]), followed by sarcoma (26 [7.6%]), adenoma (11 [3.2%]), and pulmonary neuroendocrine tumor (5 [1.5%]); there was also 1 plasmacytoma and 1 carcinosarcoma. Twenty (5.9%) sarcomas were classified as primary pulmonary histiocytic sarcoma. There was a significant difference in median survival time between dogs with pulmonary carcinomas (399 days), dogs with histiocytic sarcomas (300 days), and dogs with neuroendocrine tumors (498 days). When dogs with pulmonary carcinomas were grouped on the basis of clinical stage, there were no significant differences in median survival time between dogs that did and did not receive adjuvant chemotherapy. Results indicated that pulmonary carcinoma is the most common cause of primary pulmonary neoplasia in dogs; however, nonepithelial tumors can occur. Survival times were significantly different between dogs with pulmonary carcinoma, histiocytic sarcoma, and neuroendocrine tumor, emphasizing the importance of recognizing the relative incidence of these various histologic diagnoses. The therapeutic effect of adjuvant chemotherapy in dogs with pulmonary carcinoma remains unclear and warrants further investigation.

A RARE CASE: PRIMARY MUCINOUS CYSTIC NEOPLASM OF THE GALLBLADDER

Cystic lesions originating from the gallbladder are very rare. Mucinous cystic neoplasms of the liver and biliary system principally occur in the liver, followed by the extrahepatic biliary system. Only a few case reports were reported primarily in the gallbladder. A 63-year-old woman was admitted to our hospital with complaints of pain in the right upper abdomen, increasing after meals, and abdominal discomfort. A laparoscopic cholecystectomy was performed. Macroscopically, the cyst was localized in the serosa of the fundus. Based on immunohistochemical examination, the cyst was diagnosed as primary mucinous cystic neoplasia of the gallbladder. Although it is very rare, mucinous cystic neoplasia should be kept in mind when dealing with cystic lesions of the gallbladder. Due to serious associated problems such as the risk of malignant transformation or bile duct obstruction, particularly in larger cysts, a cholecystectomy is mandatory

A RARE CASE: PRIMARY MUCINOUS CYSTIC NEOPLASM OF THE GALLBLADDER

Cystic lesions originating from the gallbladder are very rare. Mucinous cystic neoplasms of the liver and biliary system principally occur in the liver, followed by the extrahepatic biliary system. Only a few case reports were reported primarily in the gallbladder. A 63-year-old woman was admitted to our hospital with complaints of pain in the right upper abdomen, increasing after meals, and abdominal discomfort. A laparoscopic cholecystectomy was performed. Macroscopically, the cyst was localized in the serosa of the fundus. Based on immunohistochemical examination, the cyst was diagnosed as primary mucinous cystic neoplasia of the gallbladder. Although it is very rare, mucinous cystic neoplasia should be kept in mind when dealing with cystic lesions of the gallbladder. Due to serious associated problems such as the risk of malignant transformation or bile duct obstruction, particularly in larger cysts, a cholecystectomy is mandatory

Metabolic Reprogramming of Glioblastoma Cells during HCMV Infection Induces Secretome-Mediated Paracrine Effects in the Microenvironment.

Glioblastoma (GBM) is an aggressive primary central nervous system neoplasia with limited therapeutic options and poor prognosis. Following reports of cytomegalovirus (HCMV) in GBM tumors, the anti-viral drug Valganciclovir was administered and found to significantly increase the longevity of GBM patients. While these findings suggest a role for HCMV in GBM, the relationship between them is not clear and remains controversial. Treatment with anti-viral drugs may prove clinically useful; however, their results do not explain the underlying mechanism between HCMV infection and GBM progression. We hypothesized that HCMV infection would metabolically reprogram GBM cells and that these changes would allow for increased tumor progression. We infected LN-18 GBM cells and employed a Seahorse Bioanalyzer to characterize cellular metabolism. Increased mitochondrial respiration and glycolytic rates were observed following infection. These changes were accompanied by elevated production of reactive oxygen species and lactate. Due to lactate’s numerous tumor-promoting effects, we examined the impact of paracrine signaling of HCMV-infected GBM cells on uninfected stromal cells. Our results indicated that, independent of viral transmission, the secretome of HCMV-infected GBM cells was able to alter the expression of key metabolic proteins and epigenetic markers. This suggests a mechanism of action where reprogramming of GBM cells alters the surrounding tumor microenvironment to be permissive to tumor progression in a manner akin to the Reverse-Warburg Effect. Overall, this suggests a potential oncomodulatory role for HCMV in the context of GBM.

Incidental Meckel’s diverticula low grade neuroendocrine tumor coexisting with synchronous sigmoidian and perianal adenocarcinoma

Although rarely, due to the high variability of the possible tissues encountered in it’s wall, the Meckel’s diverticula can represent a site for tumor development in 0,5-3,2% cases. Data in the literature shows that the most common malignancy at this level is represented by neuroendocrine tumors (NET) the observed incidence of neurendocrine tumors and other primary neoplasia, varies between 12-55%. Moreover, the gastro-intestinal tract was the second primary tumor bearer encountered.

Epidemiological Profile of 96 Intracranial Tumors Treated in a Single Reference Center

Abstract Objectives The present study aims to categorize the prevalence of intracranial tumors surgically treated at the neurosurgery service of Hospital Universitário Evangélico Mackenzie (HUEM) between 2016 and 2018. Material and Methods This survey included patients surgically treated due to primary or metastatic intracranial neoplasia between 2016 and 2018 at a referral center in the city of Curitiba. These patients were analyzed for epidemiological, histopathological, and topographic data, and they underwent an assessment of the outcome at the time of hospital discharge. Results A total of 96 patients met the inclusion criteria. The most prevalent tumor was the glioma, with 39.6% of the sample, with glioblastoma being the most prevalent histological type. Brain metastases and meningiomas represented, respectively, 21.9% and 18.8% of the total. There was a predominance of supratentorial and intra-axial tumors in our sample. Conclusion Glioma was the most commonly found tumor, directly associated with high morbidity and mortality. The development of new and more effective drugs with action directed at the molecular level of intracranial tumors may be the path to a longer survival and improvement in the quality of life of these patients.

533 Uncommon ECG presentation in Tako-tsubo syndrome

Abstract Aims We present the case of an 80-year-old woman without prior cardiovascular history, recent instrumental diagnosis of peritoneal carcinomatosis and ongoing oncologic diagnostic work up. Methods and results The patient was admitted to our ED for acute-onset worsening dyspnoea. On first clinical evaluation, she denied typical angina, remarkable clinical features were dyspnoea, tachycardia and hypotension. Admission ECG showed sinus rhythm with posterior and inferior ST elevation (leads DII, aVF, V5, V6) with reciprocal ST segment depression in leads V1–V2. Echocardiography confirmed infero-postero-lateral akinesia determining moderate reduction of LVEF (35–40%), normal aortic root, no pericardial effusion. Laboratory tests revealed normal WBC count, mild anaemia (HB 10.7 g/dl), normal renal function, elevated C-reactive protein (139 mg/l, n.v. &amp;lt; 8). Cardiac troponin I (cTnI) was normal on admission, with significant delta on second determination (0.012 &amp;gt; 2.5 ng/ml, nv &amp;lt; 0.023). ST elevation persisted after BP normalization and hypoxia treatment; so, taken into account the increased procedural risk due to patient’s age and comorbidities, however we decided to perform urgent coronary angiography. Surprisingly, coronary angiography revealed absence of any significant stenosis, with TIMI 3 flow in any coronary segment. The patient was then admitted to the ICU with diagnosis of MINOCA. The next day ECG revealed normalization of ST segment and Q wave in V2–V3. On day 2 new ECG showed new ventricular repolarization abnormalities with T wave inversion in precordial leads. Peak hs-cTnI was &amp;gt;15 000 ng/l. Repeat echocardiography on day 2 reported complete akinesia of all the apical segments of the LV with normo-hyperkinesia of the mid-basal segments (apical ballooning pattern) and severely depressed systolic function (FE 32–35%). During the following days patient’s symptoms improved, with rapid weaning from oxygen therapy and stable haemodynamic parameters. After 10 days the patient repeated echocardiography, which revealed improvement of global LVEF and persisting mild apical hypokinesia, suggesting the diagnostic hypothesis of Tako-Tsubo Syndrome (TTS) or TTS-phenocopy (unfortunately cardiac MRI was not performed). The patient was therefore transferred to oncology department to complete the diagnostic work-up; primary mammary neoplasia was identified, moreover associated with metastasis in the liver and the brain. Unfortunately, the patient died a month later due to non-cardiac causes. This is the case report of an uncommon MINOCA, which presented mimicking inferolateral acute STEMI, but subsequent ECG and echocardiographic evolution showed the more typical TTS pattern, with apical ballooning on echo and deep negative T waves in anterior leads. Conclusions The prevalence of MINOCA is estimated to be 6% to 8% among patients diagnosed with MI, especially women, however it is more common in patients with NSTEMI compared with STEMI; moreover in cases of TTS presenting with ST elevation, usually the elevation is found in anterior leads without reciprocal ST depression; in this patient instead ST elevation was inferolateral with reciprocal anterior ST depression. Absence of obstructive CAD and clinical/echocardiographic evolution allowed us to confirm the diagnosis of MINOCA/TTS.

Identification and treatment of primary cervical gestational trophoblastic neoplasia: a retrospective study of 13 patients and literature review

BackgroundPrimary cervical gestational trophoblastic neoplasias (GTNs) are extremely rare ectopic GTNs. Such lesions are difficult to diagnose clinically because of their rarity, with abnormal vaginal bleeding of a non-specific cause being the most common symptom. To that end, this retrospective study aimed to identify the clinical characteristics of cervical GTN and to explore diagnostic and therapeutic strategies.ResultsThirteen patients diagnosed with primary cervical GTN at the Department of Gynecology, Peking Union Medical College Hospital, Beijing, China, between June 1, 1988 and May 31, 2020 were included in the study. All patients had irregular vaginal bleeding, including six who presented with massive bleeding. Seven patients (53.8%) were initially misdiagnosed with a cervical pregnancy. All patients received chemotherapy; 11 (84.6%) also underwent hysterectomy because of chemoresistant lesions or uncontrolled bleeding. All patients achieved complete remission; however, two women (15.4%) experienced a relapse during the median follow-up period of 35 months. A comprehensive review of English-language literature published between 1980 and 2020 identified 22 case reports encompassing 27 patients. The definitive diagnosis was achieved via pathology in 26 of them (96.3%), and hysterectomy was performed in 21 (77.8%).ConclusionsOwing to its rarity and nonspecific symptoms, the diagnosis of primary cervical GTN is challenging and often relies on pathology. The combination of chemotherapy and hysterectomy is the main therapeutic strategy for this disease.

IDH Wild-type Glioblastoma Presenting with Seizure: Clinical Specificity, and Oncologic and Surgical Outcomes.

Glioblastoma (GBM) is the most common and aggressive primary brain neoplasia in adults. Seizure is a common manifestation in GBM. Up to 25 to 60% of patients with GBM have seizures. We aim to summarize all the relevant clinical, surgical, radiologic, and molecular features of a cohort of patients suffering from GBM-related epilepsy and measure the outcome, to understand the possible existence of a clinical/phenotypical specificity of this subgroup of patients. We retrospectively analyzed a cohort of 177 patients affected by isocitrate dehydrogenase wild-type (IDH-WT) GBM; 49 patients presented seizure at onset (SaO) and 128 were seizure free (SF). We investigated the relationship between seizures and other prognostic factors of GBMs. A statistically significant association between the location of the lesions in the parietal lobe and seizures was observed. The left side was more commonly affected. Interestingly, there was a statistical relationship between tumors involving the subventricular zone (SVZ) and SaO patients. The tumors were also smaller on average at diagnosis, and generalized SaOs were associated with longer overall survival. The typical patient with IDH-WT GBM with SaO is a young (<55 year) male without a history of headache. The lesion is typically small to medium in size and located in the temporoparietal dominant lobe, with a high tendency to involve the SVZ.

Non-resectable Malignant Peritoneal Mesothelioma Treated with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Plus Systemic Chemotherapy Could Lead to Secondary Complete Cytoreductive Surgery: A Cohort Study.

Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive primary peritoneal neoplasia. At diagnosis, few patients are eligible for a recommended cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Among neoadjuvant strategies, pressurized intraperitoneal aerosol chemotherapy (PIPAC) combined with systemic chemotherapy has been recently proposed. This study evaluated this strategy in a cohort of DMPM patients. Patients with DMPM and primary or recurrent non-resectable diseases who received at least one PIPAC procedure in alternation with systemic chemotherapy were included in this retrospective study to analyze oncologic outcomes. Overall, 26 DMPM patients were treated with at least one PIPAC, including 20 patients with no previous CRS. Of 22 patients (85%) who had symptoms, 9 had perceptible ascites. Overall, 79 PIPAC procedures were performed, with half of the patients receiving three PIPAC procedures or more. Among eight patients (31%), 10 adverse events (13% of procedures) were reported, including two severe complications, both corresponding to digestive perforations. Improvement of symptoms was reported for 32% of the patients, whereas control of ascites was noted in 46%. All but one procedure among 14 patients (54%) secondarily treated by CRS-HIPEC were considered complete resections. After a median follow-up period of 29.6 months (95% confidence interval [CI], 17.6-not reached [NR]), the median overall survival period was 12 months (95% CI 11.1-NR). The median progression-free survival (PFS) was significantly better among the patients who underwent resection than among those who did not (33.5 vs 7.4 months; hazard ratio [HR], 0.18; 95% CI 0.06-0.755; p < 0.001). For patients with initially non-resectable DMPM, PIPAC is feasible for treatment with neoadjuvant intent and could facilitate complete secondary resection.

Efficacy of topical Interferon Alfa- 2b used as an adjunct in the management of primary OSSN

To assess the efficacy of topical interferon alfa-2b as an adjunct therapy in the management of primary ocular surface squamous neoplasia (OSSN).: Clinically visible OSSN on slit lamp examination in 21 patients (21 tumors) was managed with topical interferon alfa-2b, 1 million IU/mL, 4times daily for a period of one month, before subjecting the patients to definitive surgery. The patients were periodically observed, over a period of 6 months. Tumor control and complications were evaluated according to American Joint Committee on Cancer classification. A significant reduction in size, was noted in smaller tumors. Final diagnosis and staging was done after histopathological examination of the surgically excised tumour, which had been excised with a 4mm margin. Bigger extensive lesion did not show appreciable response in terms of appearance or reduction of size. Tumor size was found to be reduced significantly in 19 out of 21 tumors (%) following topical interferon alfa-2b treatment for a period of 1 month, from the presentation. Of the 19 tumors, tumor surface area was reduced 44% (median). Two patients (8.3%) did not respond to the treatment.Based on American Joint Committee on Cancer classification, significant reduction was achieved in 2 of 3 Tis (67%), 17 of 20 T3 (85%), 19 of 23 N0 (83%), and 19 of 23 M0 (83%) category tumors. According to American Joint Committee on Cancer classification, significant reduction with topical interferon alfa-2b can be achieved in 67% of Tis, 85% of T3, and 83% of all OSSN.

Primary malignant neoplasms of the cecal appendix: unusual findings in acute appendicitis

Introduction: To evaluate the prevalence of appendix neoplasia correlating with patient profile, histological types and frequency. Methods: Data collection was performed in the Pathology Department of a General Hospital, with the objective of identifying patients diagnosed with malignant cecal appendix tumors by histopathologic study of specimens from acute appendicitis. Results: The prevalence of malignant primary epithelial neoplasia of the appendix was 1%. Fifty percent of the cases were neuroendocrine tumors, 35% were mucinous, and 15% were adenocarcinomas. The mean age at diagnosis was 41.3 (SD, 20.4) years (range16-81), with a women/men ratio of 3:1. Discussion: Appendiceal neoplasms are rare and should be suspected manly in women over 40 years of age with suggestive symptoms of acute appendicitis. The size, location, extent, margins and presence of mucin are essential findings for the treatment of these patients.

The association between pre-colectomy thiopurine use and risk of neoplasia after ileal pouch anal anastomosis in patients with ulcerative colitis or indeterminate colitis: a propensity score analysis.

The risk of neoplasia of the pouch or residual rectum in patients with ulcerative colitis (UC) who undergo total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is incompletely investigated. Thiopurine use is associated with a reduced risk of colorectal neoplasia in patients with UC. We tested the hypothesis that thiopurine use prior to TPC may be associated with a reduced risk of primary neoplasia after IPAA. We conducted a retrospective cohort analysis of patients from a tertiary referral center from January 2008 to December 2017. Eligible patients with UC or IC underwent TPC with IPAA and had at least two pouchoscopies with biopsies ≥ 6months after surgery. Propensity score analysis was conducted to match thiopurine exposed vs unexposed groups based on clinical covariates. Multivariable Cox regression analysis estimated the risk of neoplasia. A total of 284 patients with UC or IC (57.4% male, median age 35.6years) were analyzed. Ninety-seven patients (34.2%) were confirmed to have thiopurine exposure ≥ 12weeks immediately prior to TPC ("exposed") and 187 (65.8%) were confirmed to have no thiopurine exposure for at least 365days prior to TPC ("non-exposed"). Compared to non-exposed patients, patients with thiopurine exposure less often had dysplasia (7.2% vs 23.0%, p = 0.001) and had lower grades of dysplasia before colectomy. After IPAA, patients with neoplasia were older (44.0 vs 34.8years, p = 0.03), more likely to have had dysplasia as colectomy indication (44.4% vs 15.4%, p = 0.007), and more likely to require pouch excision (55.6% vs 10.2%, p < 0.0001), compared to patients without neoplasia. On propensity-matched cohort analysis, no factors were significantly associated with risk of primary neoplasia. Thiopurine exposure for at least the 12weeks prior to TPC in patients with UC or IC does not appear to be independently associated with risk of primary neoplasia following IPAA.

Metachronous second primary neoplasia in oropharyngeal cancer patients: Impact of tumor HPV status. A GETTEC multicentric study

IntroductionPatients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival. Material and methodsAll OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan–Meier analysis. ResultsAmong the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group. ConclusionP16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients.

Perfil de pacientes com câncer de laringe atendido nos hospitais de alta complexidade oncológica no Pará na série temporal 2000-2017

Objetivo: Traçar o perfil de pacientes com neoplasia primária de laringe em hospitais de alta complexidade oncológica no Pará na série temporal 2000-2017. Método: Estudo epidemiológico, retrospectivo realizado com a base de dados secundários provenientes do Registro Hospitalar de Câncer (RHC). Resultados: o perfil de pacientes com neoplasia maligna da laringe em serviços de alta complexidade oncológica no estado do Pará são em sua maioria: sexo masculino, maior de 40 anos, histórico de etilismo e/ou tabagismo, branco ou pardo, ensino fundamental incompleto, diagnosticados nos estágios mais avançados. Conclusão: Dessa forma, percebe-se que esta neoplasia está fortemente alicerçada na interação dos fatores ambientais e endógenos. Sobretudo, o sistema de saúde, ainda é tênue para atender aos pacientes em risco ou com a neoplasia de laringe, a começar pelos índices altos de desconhecimento presente nas bases de dados secundários sobre indicadores em saúde, o que implica na tendência de certas variáveis importantes para a predição do câncer.

Wnt2b Is Essential for Adrenocortical Progenitor Cell Fate and Zona Glomerulosa Identity in Vivo

Dysregulation of normal adrenal structure and function contributes to a spectrum of diseases from hypoplasia to cancer. Peripheral adrenocortical progenitor cells in the zona glomerulosa (zG) centripetally migrate and differentiate to replenish steroidogenic cells of the zG and the inner cortex over time. Both the fate of progenitor cells and aldosterone production by steroidogenic cells in the zG are regulated by Wnt/β-catenin signaling, but the cell-specific effects of individual WNT ligands in the adrenal cortex are not fully understood. To further characterize Wnt signaling components crucial for progenitor cell fate and zG identity, we analyzed mouse adrenals using single molecule in situ hybridization, which revealed the previously unknown expression of Wnt2b exclusively in the adrenal capsule. Wnt2b is co-expressed in the capsule with the Wnt signaling potentiator Rspo3, the loss of which causes zG depletion and reduced adrenal size in mice. Therefore, we hypothesized that capsular WNT2B activates Wnt signaling in the underlying zG to maintain the undifferentiated state of progenitor cells. To define the role of WNT2B in these processes, we first generated whole body Wnt2b knockout (KO) mice, which exhibit complete zG loss, as defined by known markers of zG identity (β-catenin and DAB2). To more fully determine the mechanism by which Wnt2b deletion results in zG loss, we crossed Wnt2b-floxed and capsule-specific Gli1-CreERT2 mice to generate a Wnt2b conditional knockout (cKO) model and study the effects of Wnt2b loss on the zG during homeostasis of the adult adrenal cortex. Gli1-CreERT2 activation by tamoxifen in 6-week-old mice significantly decreased Wnt2b expression and resulted in a lower adrenal-to-body weight ratio in Wnt2b cKOs compared to controls four weeks later. Adrenocortical proliferation (Ki67) was also significantly decreased in Wnt2b cKO mice, suggesting that WNT2B may promote progenitor cell self-renewal. To characterize the consequences of WNT2B loss on canonical Wnt signaling, we assessed activation of β-catenin, the primary Wnt signaling effector. High β-catenin activity in the zG observed in wild-type mice was disrupted in Wnt2b cKO mice, together with markedly reduced expression of adrenocortical Wnt target genes Axin2 and Wnt4. In addition, Wnt2b loss resulted in downregulation of steroidogenic genes Cyp11b2 and Hsd3b6. Together, these data reveal that capsule-derived WNT2B is required for zG differentiation and maintenance, potentially through activating adrenocortical Wnt/β-catenin signaling and downstream target gene expression involved in both progenitor cell fate and steroid-producing cell function. Studies to more fully elucidate the dynamic effects of WNT2B on the adrenal zG are ongoing as they have important implications for adrenal homeostasis and disease, including both primary adrenal failure and neoplasia.