Low Metastatic Rate Research Articles

Fine needle aspiration cytology for diagnosis of canine cutaneous transmissible venereal tumor and its successful therapeutic management

Canine transmissible venereal tumour (CTVT) is a well-documented transplantable tumour in dogs, with no breed or sex predilection and a low metastatic rate. The present short communication reports a case of naturally occurring multicentric TVT in a male dog with a unique cutaneous involvement. A 13-year-old intact male German-Shepherd was presented with multiple nodular lesions disseminated over the face, neck, left forelimb, caudal to left shoulder and abdomen regions. Grossly the lesions were non-fluctuating, nodular, rapidly growing and ulcerated in few growths, measuring up to 2-5 cm in diameter. A rapid and precise diagnosis was made based on fine needle aspiration cytology (FNAC) of nodules and an impression smear of ulcerated lesions. Hematology revealed leucocytosis with marked neutrophilia. FNAC of cutaneous nodule revealed neoplastic population of round cells having characteristic cytoplasmic vacuolation typical of TVT. Based on the anamnesis and cytological examinations the case was diagnosed as primary cutaneous TVT in a progressing growth phase. Chemotherapy with vincristine sulphate resulted in complete resolution of clinical signs and recovery. The effects of the treatment and regression of tumour were also assessed post-therapy by cytology.

RhoG/Rac1 signaling pathway involved in migration and invasion of salivary adenoid cystic carcinomacells.

This study aimed to explore whether RhoG/Rac1 was involved in migration and invasion of salivary adenoid cystic carcinoma (SACC). RhoG and Rac1 were evaluated in two SACC cell lines, namely SACC-83 and SACC-LM, with low and high rates of lung metastasis, respectively. Functional changes were evaluated using cell proliferation, transwell, and wound-healing assays, and molecular events were investigated using real-time PCR and Western blot assays. RhoG and Rac1 were highly expressed and more activated in SACC-LM cells than in SACC-83 cells. RhoG overexpression promoted SACC-83 cell migration and invasion through activating Rac1. The knockdown of RhoG or Rac1 partially blocked epiregulin-induced migration and invasion in SACC-83 cells. Epiregulin-induced activation of RhoG/Rac1 in SACC-83 cells was blocked by a Src inhibitor, or an AKT inhibitor or AKT siRNA, or an ERK1/2 inhibitor. Moreover, the epiregulin-induced phosphorylation of AKT and ERK1/2 in SACC-83 cells was blocked by a Src inhibitor, and the epiregulin-induced phosphorylation of ERK1/2 was blocked by an AKT inhibitor or AKT siRNA. Overexpression of activated AKT induced activation of ERK1/2 and RhoG. RhoG/Rac1 signaling pathway was involved in SACC cell migration and invasion. RhoG/Rac1 at least partially mediated epiregulin/Src/AKT/ERK1/2 signaling to promote SACC cell migration and invasion.

The balance of serum IL-18/IL-37 levels is disrupted during the development of oral squamous cell carcinoma

Growing evidences have demonstrated a pivotal role of chronic inflammation in oral squamous cell carcinoma (OSCC) through the modulation of inflammatory cells and cytokine production. IL-37 is newly discovered anti-inflammatory member of IL-1 family and can bind to IL-18 receptor to inhibit IL-18 (pro-inflammatory member of IL-1 family) function. Investigation on the balance of IL-18/IL-37 would provide new insights into the function of IL-1 family in OSCC. Thus, serum IL-18 and IL-37 levels of OSCC patients (n = 108), leukoplakia patients (n = 40), and healthy donors (n = 36) were collected to analyze the balance of IL-18 and IL-37, and also determine their diagnostic value and prognostic significance in OSCC. The results showed that OSCC patients had high IL-18 and low IL-37 levels in serum and peripheral blood mononuclear cell (PBMC). The ratio of IL-18/IL-37 in serum efficiently distinguished non-cancer individuals from OSCC patients (cut off value: 2.15). Moreover, patients with high IL-18 and low IL-37 were susceptible to develop advanced tumor stage and lymph node metastasis (Odd ratios of IL-18/IL-37 is 4.903 and 12.613, respectively). Meanwhile, higher IL-18/IL-37 ratio could predict shorter overall survival and disease-free survival of OSCC patients, although it was not an independent prognostic factor. We further analyze the correlations of serum IL-18/IL-37 with immunocytes in peripheral blood and found that high IL-18 level was associated with more CD19+ B cells, while serum IL-37 seem to be associated with reduced percentage of CD3+CD8+ T cells, indicating its balance could change the adaptive immune response. Unexpectedly, we first revealed the different function of IL-18/IL-37 in serum and tumor tissues. High mRNA expression of IL-18 in tumor tissues correlated with low lymph node metastasis rate and low tumor stage, which was contradictory to the pro-tumor role of IL-18 in serum. In conclusion, enhanced ratio of IL-18/IL-37 level in serum could be an efficient biomarker for OSCC. Its balance might regulate CD19+ B cells and CD3+ CD8+ T cells for OSCC progression.

Enterectomia en el tratamiento del carcinoide neuroendocrino obstructivo en un perro: relato de caso

Carcinoids in dogs are rare neoplasms of the diffuse neuroendocrine cell system. The term neuroendocrine tumor has been proposed and the clinical manifestation is related to the location. Despite the low rate of growth and metastasis, such neoplasms are often malignant and must undergo surgical resection. When this is done properly, the outcome is usually satisfactory. The objective of this study was to describe a case of carcinoid in a 10-year-old female with tenesmus and presence of fecaloma. The patient was received at a private veterinary clinic and, after clinical consultation and imaging examinations, she was submitted to the enterotomy and removal of fecaloma in the descending colon. The obstruction of the intestinal flow was resulting from a neoplastic mass in a pre-pubic region, also resected and forwarded for analysis. The histopathological revealed neuroendocrine carcinoid and the dog was followed for 60 days after the procedure, without signs of recurred or metastasis. Therefore, it is understood that neuroendocrine carcinoids should be considered as a cause of tenesmus and constipation in dogs, especially in the elderly, and the prognosis is favorable when patients undergo the surgical procedure with adequate resection of the tumor.

Electrochemotherapy induces tumor regression and decreases the proliferative index in canine cutaneous squamous cell carcinoma

Canine cutaneous squamous cell carcinoma (cSCC) is the most common skin cancer in dogs, and, due to its low metastatic rate, local treatments, such as electrochemotherapy (ECT), promote disease control or even complete remission (CR). This study aimed to evaluate the gene and protein expression of Bcl-2 and Bcl-2 associated X protein (BAX), the proliferative index and clinical parameters in dogs with cSCC subjected to ECT. A prospective nonrandomized clinical study was performed using dogs with naturally occurring cSCC that was treated with ECT. Eighteen lesions from 11 dogs were selected. The tumor size at day 0 (D0) had no impact on survival or prognosis (P > 0.05). Tumor samples had a lower proliferative index after ECT (D21) than before ECT (P = 0.031). The survival of subjects with Ki67 values lower and higher than the Ki67 median value were not significantly different (P > 0.05). Regarding apoptotic markers, there were no significant differences in the gene and protein expression levels of BAX or Bcl-2 at D0 and D21 (P > 0.05) or in the overall survival of subjects with different levels of apoptotic markers. In conclusion, there was no change in BAX or Bcl-2 gene and protein expression in response to ECT at the time points evaluated, but ECT was able to reduce tumor volume and cellular proliferation in cSCC.

Brain malignancies: Glioblastoma and brain metastases.

Brain, the major organ of the central nervous system controls and processes most of body activities. Therefore, the most aggressive brain tumor - glioblastoma and metastases from other organs to the brain are lethal leaving the patients with very short time of survival. The brain tissue landscape is very different from any other tissues and the specific microenvironment, comprising stem cells niches and blood-brain barrier, significantly influences the low rate of glioblastoma metastasis out of the brain, but better accommodates brain-invading cancer. In contrast to low frequency (0.5%) of all glioblastoma metastases, 10%-45% of other primary cancers do metastasize to the brain. This review addresses general cellular and molecular pathways that are to some extent similar in both types of metastases, involving circulating tumor cells (CTCs) with cancer stem cells (CSCs) characteristics, and metastatic niches. The invasion is a dynamic process involving reversible epithelial-to-mesenchymal (EMT) cell process, creating a transient gradient state that is inter-connected with epigenetic plasticity of the metastasizing (m)CSCs. These cells can switch between stationary, low proliferating/dormant state to a migratory, mesenchymal-like state. Settling in their respective niches as dormant CSCs in the secondary organ is a common feature in all types of metastases. In glioblastoma metastasis, the malignant mGSC cells express markers of mesenchymal GSC subtype (MES-GSC), such as CD44 and YK-40 and their major obstacle seems to be propagating in the in various organs' microenvironments, different from the niches that home GSCs in the primary glioblastoma. Focusing on one stromal component in the glioblastoma niches, the mesenchymal stem cells (MSCs), we report herein on their differential effects on glioblastoma cells, highly depending on their genetic subtype. On the other hand, in brain metastases, the major hindrance to metastatic progression of mCSCs seem to be crossing the blood-brain-barrier. Novel therapeutic approaches for brain metastases from various cancer types are advancing slowly, and the general trends involve targeting metastatic sub-clones and selective determinants of their niches. The update on the four most common brain metastases from lung, breast, melanoma and colorectal carcinoma is presented.

Current status of treatment for osteosarcoma of head and neck

Head and neck osteosarcoma is a rare tumor. Its clinical features and recurrence pattern are different from those of osteosarcoma in other parts. Osteosarcoma of the head and neck occurs late with a high local recurrence rate and a low distant metastasis rate. Local recurrence is the main cause of death. Surgery is the main treatment. Postoperative radiotherapy is recommended for patients with positive surgical margin, proximal incisional margin and uncertain surgical margin. The role of chemotherapy remains controversial. Effective molecular targeted therapeutics need to be further explored for recurrent, metastatic and unresectable osteosarcoma, . Key words: Osteosarcoma/radiotherapy; Osteosarcoma/chemotherapy; Osteosarcoma/other therapy

Myxoinflammatory Fibroblastic Sarcoma of Eyeball in an Infant: A Rare Presentation.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue neoplasm most commonly occurring in the distal extremities of adult patients. It is a low-grade neoplasm with high rate of local recurrence but low rate of metastasis. We describe a case of MIFS of eyeball in an infant. An enucleation surgery was performed, and on the basis of histopathological and immunohistochemical evaluation, a diagnosis of MIFS was rendered. Till date more than 400 cases of MIFS have been reported with only a single case report of MIFS in an adult in iris. To the best of our knowledge, ours is the first case of MIFS in the eye in a child. Considering its rarity in children and especially in an infant (this seems to be the youngest patient in the literature), close follow-up is essential as the biology of these lesions cannot be predicted.

Cutaneous keratinocyte cancers of the head and neck: Epidemiology, risk factors and clinical, dermoscopic and reflectance confocal microscopic features

Keratinocyte cancers are the most common malignancy among people with European ancestry, and are very common on sun-exposed areas of the head and neck. Incidence is directly correlated with latitude and annual ultraviolet radiation incidence, although there are a number of other environmental, occupational and genetic risk factors, and keratinocyte cancers become more common at middle age. Basal cell carcinomas (BCC) are the most common, comprising 80% of keratinocyte cancers, but have a very low rate of metastases and low mortality. Squamous cell carcinomas (SCC) make up 20% of keratinocyte cancers, and have relatively infrequent metastases, at 5–16%. While there are no precursor lesions for BCC, SCC represents the final stage in a spectrum of cellular atypia and dysplasia, from actinic keratoses to in situ SCC to invasive SCC. Dermoscopy is a well-established diagnostic tool for keratinocyte cancers, and reflectance confocal microscopy is emerging as another useful diagnostic tool, particularly on functionally and cosmetically sensitive sites like the face.

Active Surveillance for Small Papillary Thyroid Cancer: A Systematic Review and Meta-Analysis.

Background: The rapid increase in the incidence of small papillary thyroid carcinoma (PTC) appears to be caused by the detection of small thyroid cancers. Active surveillance (AS) was therefore suggested to overcome this problem. As the results were favorable with low rates of size enlargement and lymph metastasis, the 2015 American Thyroid Association Management Guidelines endorsed AS as an alternative to immediate surgery. As the clinical value of AS is a subject of ongoing active discussions and surveys, we considered a systematic review and meta-analysis to be timely and necessary. Methods: Ovid-MEDLINE and EMBASE databases were searched up to January 5, 2019, for studies reporting patients who were followed up with AS for PTC. Data extraction and methodological quality assessment were performed independently by two radiologists. The primary outcomes were to identify the annual pooled proportions of size enlargement of 3 mm or more and the detection of lymph node metastases at a 5-year follow-up period. These were calculated using an inverse-variance weighting model. An additional outcome was evaluation of the reasons for surgery during AS. Results: The pooled proportion of size enlargement occurring at 5 years was 5.3% [95% confidence interval (CI), 4.4-6.4%], and the pooled proportion of 5-year lymph node metastasis was 1.6% [CI, 1.1-2.4%]. In many subjects undergoing delayed operations, the reasons for operation were often other than those of size enlargement or lymph node metastasis. Conclusions: AS is effective for the management of small PTC, with a low proportion of size enlargement or lymph node metastasis occurring at 5 years. However, a substantial proportion of the causes of delayed surgery were other than size enlargement or lymph node metastasis, and these situations need to be optimally managed.

Local surgical treatment of cutaneous squamous cell carcinoma: deficits and controversies in the literature.

The prognostic impact of primary excision in the treatment of cutaneous squamous cell carcinoma depends on certain tumor characteristics (risk factors), the surgical approach chosen and the subsequent histological examination. For the development of the AWMF (Association of Scientific Medical Societies in Germany) guidelines for squamous cell carcinoma, the most conclusive guidelines available were evaluated using the DELBI tool (German Instrument for the Methodological Appraisal of Guidelines). These were the Scottish and Canadian guidelines as well as the joint guidelines published by EDF, EADO and EORTC. The primary literature on the aforementioned topics that was used for these guidelines included 49 studies and 9 reviews. None of the studies had a prospective, randomized design; 19 studies contained prospective data; 30 studies provided retrospective data. Overall, the results were heterogeneous. Not only were there discrepancies in terms of the validity of the various risk factors for locoregional disease progression - such as dedifferentiation, desmoplasia and perineural invasion - but also with respect to tumor thickness and surgical consequences. Differences were also found regarding the histological processing method used. In general, there are two such methods: conventional histology (bread loaf technique) and complete histological assessment of excision margins. The latter was found to be associated both with low recurrence rates and low metastatic rates, possibly due to the fact that patients treated with the latter method had lower-risk tumors. Publications on bread loaf histology lacked precise information as to how the tissue was actually processed. Likewise, there was a lack of usable data in terms of the surgical margins used in the primary excision. Conclusion: The current literature is inconsistent and insufficient with regard to the various prognostic factors and the surgical approach to cutaneous squamous cell carcinoma.

The effect of metformin use on hypopharyngeal squamous cell carcinoma in diabetes mellitus patients

BackgroundMetformin is proven to improve the prognosis of various cancers, but it is unknown if metformin could ameliorate hypopharyngeal cancer in diabetes mellitus patients. This was a retrospective cohort study, and the effect and survival outcome of metformin on hypopharyngeal cancer with diabetes mellitus was investigated.MethodsThere were 141 hypopharyngeal cancer patients collected in a tertiary referral center from December 1st, 2011 to December 31st, 2013. There were 49 patients without diabetes mellitus (DM) and 92 patients with DM. In the 92 DM patients, there were 43 patients with metformin used and 49 patients without metformin used. All received patients followed up until September 1st, 2015.ResultsThere was no significant difference in patients’ characteristics between the non-DM and DM groups, and also no significant difference in clinical T stage, N stage, metastatic condition, and disease stage between the non-DM and DM groups. DM with metformin patients had lower metastasis rates and better overall survival (OS) (p = 0.011) and disease-free survival (DFS) (p = 0.004) compared to non-DM and DM without metformin. Multivariate analysis also showed a better OS and DFS in DM-Met (+) with advanced hypopharyngeal cancer but not in early stage.ConclusionThere was less distant metastasis and better survival outcomes in hypopharyngeal cancer DM patients who use metformin.

Routine Lateral Level V Dissection May Not Be Necessary for Papillary Thyroid Microcarcinoma With Lateral Lymph Node Metastasis: A Retrospective Study of 252 Cases.

Background: Lateral lymph node metastasis (LLNM) is associated with distant metastasis, locoregional recurrence and cancer-specific mortality, although the prevalence of LLNM among patients with papillary thyroid microcarcinoma (PTMC) is relatively low. The potential benefits and risks of routine lateral level V dissection (LVD) for PTMC with LLNM have not been previously investigated.Methods: A total of 6,880 consecutive PTMC patients who underwent initial surgery at the First Hospital of Jilin University from January 2009 to July 2017 were retrospectively analyzed. A total of 252 N1b PTMC patients were enrolled in our study.Results: The overall and occult metastasis rates in level V lymph nodes were 21.4 and 6.4%, respectively. Patients with N1b PTMC who received LVD did not show a significantly lower disease-free survival (DFS) than that of patients who did not receive LVD [hazard ratio = 1.11 (CI 0.38–3.21); p = 0.85]. Meanwhile, LVD simultaneously increased the hospital stay and cost (p = 0.03; 0.02). Multivariate logistic regression analysis revealed that 3-level simultaneous metastasis in the lateral neck was an independent risk factor for level V metastasis [odds ratio = 8.6 (CI 1.42–51.72); p = 0.02].Conclusions: Because of the low metastasis rate in level V lymph nodes, the lack of benefit for recurrence, the longer hospital stay and the higher cost associated with LVD, N1b PTMC patients without clinical level V metastasis may not need to undergo routine dissection. Prophylactic LVD may be recommended only for patients with N1b PTMC with 3-level simultaneous metastasis.

Intralesional Corticosteroids for Long-term Control of Primary Cutaneous Marginal Zone Lymphoma without systemic involvement

Primary cutaneous marginal zone lymphoma (PCMZL) is a B cell lymphoma with a very low metastatic rate. Radiographic monitoring for internal involvement may be indicated initially. Favored treatments include radiation and excision. Radiation has high risk of local recurrence. Excision carries risk of infection and scarring. We report successful long-term treatment of recurrent PCMZL via intralesional steroid injections into new lesions as they arose. This was preferred by the patient over her prior radiation and surgical treatments. Intralesional steroids have the advantages of being simple and well tolerated, without exposure to ionizing radiation, or to the infection and scarring associated with surgery.

Abstract 59: The pioneer transcription factor FOXA2 regulates integrin alpha 1 expression controlling prostate cancer bone colonization

Abstract Introduction. Approximately 30,000 men will die from prostate cancer (PCa) in 2018. When localized and detected early, it has a low rate of progression and metastasis, with successful treatment. However, some patients may progress to a more lethal castrate-resistant PCa. While this occurs, frequent bone metastases will arise, and patient prognosis typically falls to 3-5 years due to lack of therapy available. The purpose of this study was to unveil the mechanisms of PCa bone colonization, allowing us to identify novel targeted therapies to prevent and treat PCa. Methods. Gene expression profiling studies revealed a subset of metastatic PCa samples express the pioneer forkhead transcription factor, FOXA2. Consistently, we found FOXA2 abundance in a sample set of human PCa bone metastases, which may suggest a functional role for FOXA2. Protein analysis of common PCa cell lines revealed high levels of FOXA2 in aggressive bone metastatic PCa PC3 cells. To understand the role of FOXA2 in PCa metastasis, FOXA2 was stably knocked down in PC3 cells. Results. PC3 cells with FOXA2 knocked down (FOXA2-KD) failed to generate in vivo bone destruction following intra-tibial injection contradictory to their parental cell line. To elucidate how FOXA2 is orchestrating these changes, we assessed the expression of all integrins and observed that loss of FOXA2 decreased mRNA and protein expression of the collagen-I binding integrin α1. Furthermore, we found FOXA2-KD decreased PC3 cells’ adhesion, spreading, and downstream Integrin α1 signaling cascades on collagen-I (a major component of bone ECM) coated surfaces. Additionally, a neutralizing antibody to integrin α1 was administered to PC3 Control cells, prompting the same adhesion pattern, solidifying that this integrin is critical to collagen-I adherence. Through ChIP analysis, we learned that FOXA2 directly regulates the ITGA1 gene promoter. Lastly, we overexpressed integrin α1 in PC3 FOXA2-KD cells and rescued the adherence properties. Conclusions. Taken together, the FOXA2-controlled expression of integrin α1 resulted in changes to adherence, spreading, and integrin signaling, providing a mechanism for how PCa cells colonize the bones. Funding: This research is supported by DOD grant (W81XWH-12-1-0212), NIH grants (R03 CA212567 and R01 CA226285), LSUHSC startups (FWCC and Office of Research) to XY, and Carroll Feist Pre-doctoral Fellowship to ZC. Citation Format: Zachary M. Connelly, Shu Yang, Nazih Khater, A. Wayne Orr, Renjie Jin, David Degraff, Colm Morrissey, Eva Corey, Robert Matusik, Xiuping Yu. The pioneer transcription factor FOXA2 regulates integrin alpha 1 expression controlling prostate cancer bone colonization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 59.

Patients with Small Renal Masses Undergoing Active Surveillance-Is Yearly Chest Imaging Necessary?

INTRODUCTION AND OBJECTIVES:Active surveillance (AS) is recognized as a standard for the management of small renal masses (SRM). Renal cell carcinoma (RCC) can metastasize to the lungs, so yearly chest imaging has been indicated for the follow-up of patients with SRM on AS. However, given the low rates of metastasis from SRM and the potentially increased rates of incidental non-RCC related findings, the necessity of this yearly chest imaging comes into question.METHODS:We performed a retrospective analysis of 268 patients with SRM enrolled in the AS arm of the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry at our institution. Chest imaging reports were examined to identify patients with abnormal findings, which were then determined to be actionable or non-actionable based on receipt of further clinical investigations/interventions.RESULTS:Of the 268 patients, 51 (19%) were found to have abnormal baseline chest images; of these 51 images, 22 (43%) were actionable or eventual...

Hospitalization cost and length of stay in pancreatic cancer population: A national inpatient database study.

e15793 Background: Pancreatic cancer accounts for 7% of all cancer deaths in the U.S. It contributes to burgeoning health care cost and is associated with poor prognosis. The aim of this study was to describe the disease burden, pattern of resource utilization, hospital cost and outcomes among hospitalized pancreatic cancer patients based on the location of disease. Methods: We conducted a retrospective study utilizing the 2014 national inpatient sample database. Adult records with a primary discharge diagnosis of pancreatic cancer were included. Records with no specification on cancer location were excluded. Regression models (logistic and linear) were used to estimate adjusted odds ratios (OR), mean length of stay (LOS) and hospital charges (HC). Covariates included sociodemographic factors, co-morbidities and therapeutic surgical procedures received during hospitalization. Results: A total of 4,799 discharge records met the inclusion criteria. Overall, 74.3% had cancer in the pancreatic head and 25.6% had cancer in the body and tail. Pancreatic head cancers were more common in whites (73%). Patients with cancer in the body and tail more commonly experienced metastasis than patients with pancreatic head cancer (23.8% versus 20.4% p = 0.02). Compared to pancreatic head cancers, patients with body and tail cancers were more likely to have a pancreatectomy during index hospitalization (OR 45, 95% CI 27.8 - 65.2). Alternatively, cancers of the pancreatic head were more likely to have an endoscopic pancreatic procedure during index hospitalization compared to body and tail (OR 7.39, 95% CI 3.9 -13.9). Pancreatic head cancers were associated with a significantly longer mean hospital LOS (8.1 versus 6.4 days, mean difference 1.66, p < 0.001) and higher mean cost of hospitalization (Mean HC $85,263.40 versus $56,156.60 p < 0.001) compared to cancer in the body and tail. Conclusions: Despite lower rate of metastasis and pancreatectomy, patients hospitalized for pancreatic head cancers have longer hospital LOS and higher healthcare cost burden. Our findings may inform physicians, patients, and policymakers and may help channel resources toward specific patient population to reduce healthcare cost and improve outcomes for individuals and healthcare organizations.

Assessment of the Rate of Skip Metastasis to Neck Level IV in Patients With Clinically Node-Negative Neck Oral Cavity Squamous Cell Carcinoma

The rate of skip metastasis to neck level IV in patients with clinically node-negative neck (cN0) oral cavity squamous cell carcinoma (OCSCC) remains controversial. To provide a high level of evidence using a meta-analysis on the rate of skip metastasis to level IV in this subset of patients. The Embase, PubMed, and Google Scholar databases were searched for articles published during the period of January 1, 1970, through December 31, 2017, using the following key terms: neck dissection, N0 neck, squamous cell carcinoma, skip metastasis, radical neck dissection, lymph node management, neck metastasis, oral cavity cancer, and tongue cancer. Some terms were also used in combination, and the reference section of each article was searched for additional potentially relevant publications. Data were analyzed from January 8 through 11, 2018. Inclusion criteria were all cohorts, including from any randomized clinical trial, case-control study, case study, and case report; studies of patients with the histopathologic diagnosis of OCSCC; and studies that differentiated data between skip metastasis and sequential metastasis to neck level IV. Of the 115 articles retrieved from the literature, 11 retrospective studies and 2 prospective randomized clinical trials (n = 1359 patients) were included. Meta-analysis of Observational Studies in Epidemiology guidelines were followed. Fixed-effects model and 95% CIs were estimated, and data of included studies were pooled using a fixed-effects model. Overall proportion of neck involvement and the rate of level IV skip metastasis. Subgroup analysis for primary site and tumor staging. The rate of level IV involvement in patients with cN0 ranged between 0% and 11.40% with a fixed-effects model of 2.53% (95% CI, 1.64%-3.55%). The rate of skip metastasis ranged from 0% to 5.50% with a fixed-effects model of 0.50% (95% CI, 0.09%-1.11%). The rate of level IV skip metastasis did not increase significantly in cases that involved neck levels I through III. Tumor staging and primary site tumor did not significantly affect the rate of skip metastasis. This meta-analysis showed very low rates of skip metastasis to neck level IV in patients diagnosed with cN0 OCSCC. Encountering an allegedly positive lymph node during neck dissection does not portend high rates of level IV involvement. Supraomohyoid neck dissection is therefore adequate for this subset of patients.

Treatment plan and prognosis of salivary adenoid cystic carcinoma with lung metastasis

Salivary adenoid cystic carcinoma (SACC) is a common malignant tumor in the oral and maxillofacial region and accounts for approximately 3%-5% of all head and neck carcinomas. SACC always occurs in the palatal salivary gland and parotid gland. The tumor has the characteristics of strong invasion, perineural invasion, high hematogenous metastasis, and low lymph node metastasis rate. The biological characteristics of SACC determine the specificity of clinical treatment. Thus far, few clinical trials have investigated the efficacy of systemic therapy owing to the rarity of SACC with lung metastasis. Moreover, long-term results are poor, and no consensus on standard treatment has been reached yet. This systematic review aims to provide a retrospective analysis of treatment options and prognosis for SACC with lung metastasis and evidence for future clinical treatment.

Bovine papillomavirus E5 oncoprotein expression and its association with an interactor network in aggresome-autophagy pathway

E5 protein, the major oncoprotein of bovine Deltapapillomavirus (BPV), was found to be expressed in 18 of 21 examined urothelial cancers of cattle. E5 oncoprotein was found to interact with p62 which was degraded through the autophagosome-lysosome pathway as well as LC3-II and appeared to be involved in the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α). Autophagy was morphologically documented by transmission electron microscope (TEM) through the detection of double-membrane autophagosomes and autolysosomes. Overexpression of Bag3 known to mediate selective autophagy was also demonstrated. Furthermore, Bag3 and BPV E5 oncoprotein were seen to co-localize with dynein and 14-3-3γ, which suggested that Bag3 could be involved in inducing the retrograde transport of BPV E5 along microtubules to aggresomes, perinuclear sites with high autophagic flux. Electron dense perinuclear structures consistent with aggresomes were also documented by TEM in urothelial cancer cells. Finally, Bag3 was found to also interact with synaptopodin 2 (Synpo2), which would seem to contribute to cargo degradation as it has been shown to facilitate autophagosome formation. This study provides mechanistic insights into the potential role(s) of autophagy in BPV disease, which can help to develop future treatment and control measures for BPV infection. Activation of autophagy correlates positively with BPV infection and may play a role in biological behavior of bladder cancer as urothelial carcinomas of cattle are known to be characterized by a relatively low rate of metastasis.