years TNM staging system has been used clinically in predicting prognosis. In early cases of oralsquamouscellcarcinoma, however, there are many patient who die despite the fact that their neoplasm were considered clinically to be stage I and II and were treated accordingly. In such patient a combined assessment of clinical staging and of cytomorphology of neoplasm might serve as more precise measure for predicting the outcome of neoplasm and for determining their treatment. (Chang, 2002) Many study of squamouscellcarcinoma correlating histologic malignancy grading with different clinical parameter such as clinical staging, recurrence and prognosis has been published. Broder’s initiated quantitative grading of cancer. His classification system has been used for many years in squamouscellcarcinoma and based on proportion of neoplasm resembling normal squamous epithelium. A lack of correlation between Broder’s degree of differentiation and prognosis, however, been reported. One of main reason being that squamouscellcarcinoma usually exhibits a heterogenous cell population with differences in degree of differentiation. So, multifactorial malignancy grading system was developed to obtain a more precise morphologic evaluation of growth potential of squamouscellcarcinoma in head and neck region. This malignancy grading system has been used during last few years in both its original form and modified version, especially for reterospective studies of squamouscellcarcinoma. (Anneroth et al., 1984) Thus, in our study we reviewed three gradingsystems along with their prognostic value.
We investigated expression levels of Nicotinamide N-Methyltransferase (NNMT), an enzyme involved in the biotransformation of many drugs and xenobiotic compounds, in oralsquamouscellcarcinoma (OSCC). Measurements were performed by semi- quantitative RT-PCR and quantitative real-time PCR in tumor and matched adjacent healthy tissue. Interestingly, NNMT was up- regulated in most of the favorable OSCCs, while no marked NNMT expression alterations between tumor and normal mucosa were detected in most of the unfavorable OSCCs. Western blot and immunohistochemical analyses also were performed and the relationship between tumor characteristics and NNMT levels in OSCC were studied to evaluate the effectiveness of NNMT as a prognostic marker in the squamouscellcarcinoma of the oral cavity. In summary, the present study suggests that NNMT may have potential as a biomarker and a therapeutic target for OSCC.
Oda T et al. proposed three mechanisms of alteration of cadherin-mediated cell adhesion system in human cancers in vivo and in vitro. The first is down-regulation of E-cadherin expression and its gene mutation . Exist- ence of altered E-cadherin expression in human cancers and a significant relationship between reduced E-cadherin expression and clinicopathological factors, such as dedif- ferentiation, invasiveness, or metastasis was previously reported . The second is abnormality or deletion of catenins [13,14]. The third abnormality is biochemical modification of catenins. It has been demonstrated that tyrosine phosphorylation of β-catenin induced by various factors (eg. v-src, hepatocyte growth factor and epidermal growth factor) suppresses E-cadherin function in vitro .
In the present study, the idea was that if some CSCs get trapped in the neck nodes, these will generate the similar spheres in culture as formed in case of tongue tumors. Since neck nodes can be available in large amounts and are more proliferative so would be an ideal in vitro system for future studies on CSCs in primary culture. In node, however, only small cell clusters were formed in CD44+ cells cultures (Figure 3A, c) possibly because of low number of these cells or competing markers on various cells for CD44 + ve magnetic beads. We observed that sphere formation is correlated with the nodal involvement of cancer because pathologically node positive OTSCC produced cell spheres in large numbers correlating with worse prognosis. Comparative account of these spheres in various stages of cancer can be studied giving clues regarding progress of disease and metastasis. In head and neck cancer, lymphnodemetastasis has been linked with poor prognosis and distant metastasis . In order to metastasize, cancer cells must first detach from the primary tumor and invade blood vessels or lymphatics either by a passive process where cells are simply sloughed off from the primary tumor or an active one involving directed migration . While some gene expression studies have suggested that distant metastases resemble their primary tumors of origin  other studies have indicated that the expression of specific genes is altered in metastatic cells . It can be assumed that the altered expression of a limited number of genes may render a sub-population of cells fully competent for metastasis, without changing its overall similarity with the primary tumor. A rise in number of circulating CSCs would correlate with the possibility of metastasis. There is an urgent need for information on the possible molecular mechanisms mediating the self-renewal of CSCs by their characterization at the genetic and proteomic level. Comparison of normal and cancer stem cells may provide a starting point for identifying proteins responsible for driving these mechanisms. The results of this preliminary study provide the means for generating CSCs that we will use for in-depth ‘omics analysis.
The OSCC presents a variable incidence of CLNM, reported between 0.9% to 36% and it has been widely accepted that CLNM dramatically reduce long-term survival and prognosis. Several predictive factors have been proposed to be correlated with the risk of contralateral lymphnodemetastasis, such as tumor location, size or thickness, ipsilateral lymphnode metástasis, ECS, TNM stage, surgical margins, grade of hystological differentiation, tumor satellite distance, perineural and lymphovascular invasion, peritumoral inflammation and local recurrence. It is important for clinicians to pay careful attention to these prognostic variables that must be globally considered for each individual case. Surgeons should take into account the detailed and individual study of risks and potential benefits of elective neck treatment for contralateral N0 neck while considering a small percentage of patients with oralcarcinoma that finally develop CLNM.
Penile carcinoma is an uncommon urological tumour and provides an opportunity for curation on early stage of the disease. Nodal metastases are one of the most important prognostic factors for survival although detection of inguinal adenopathies could be related with an inflammatory or infectious etiology. A suspicion of bilateral metastasic nodal involvement should be taken with caution. Radical inguinal lymphadenectomy has been associated to a great deal of complications. Several anatomical studies have reported the true lymphatic drainage pathways in order to reduce the area of groin dissection. Nonetheless, a prophylactic modified inguinal lympha- denectomy should not be a systematic surgical procedure in all patients due to morbidity and questioned usefulness when there are not nodal metastasis. Classical imaging studies have a limited contribution to the diagnosis of lymphnodemetastasis. Nowadays, lymphnode involve- ment may be diagnosed both minimally invasive and noninvasive techniques, such as dynamic sentinel lymphnode biopsy in intermediate and high risk patients with nonpalpable lymph nodes, and fine needle aspiration biopsy in cases with palpable nodes. Their high effectiveness has facilitated the radical pelvic or inguinal lymphadenectomy that is only performed when there is histological confirmation of nodal involvement. A new video endoscopic technique has been de- veloped at present to reduce postoperative complications although prospective studies are needed to assess outcomes. The appearance of adenopathies after surgical treatment of the primary tumour could be supported at the same guidelines. An inguinal lymphadenectomy should be carried out in selected patients to support a benefit on early stages with an extended survival.
Abstract: Two decades ago, lymphatic mapping of sentinel lymph nodes (SLN) was introduced into surgical cancer management and was termed sentinel node navigated surgery. Although this technique is now routinely performed in the management of breast cancer and malignant melanoma, it is still under investigation for use in other cancers. The radioisotope technetium ( 99m Tc) and vital blue dyes are among the most widely used enhancers for SLN mapping, although
of tumor . nm23 has antimetastatic function in normal cell growth; thus, its low expression may contribute to me- tastasis and poor prognosis among various tumors, includ- ing breast cancer, ovarian cancer, liver cancer, stomach carcinomas, and melanomas . Low nm23 expression was associated with lymphnode and liver metastases in gastric cancer . LSCC patients with low nm23 expres- sion exhibited significantly shorter survival than those with high nm23 expression . High nm23 expression is asso- ciated with favorable prognosis and may be used to evalu- ate the risk of recurrence in laryngeal carcinoma [17, 18]. Although KAI1 and nm23 are closely related with tumor metastasis, their specific roles in lymphangiogenesis and lymphatic metastasis of LSCC still need to be studied.
Abstract: Objective: To investigate clinical characteristics and prognostic factors of patients with lymph nodes me- tastasis (LNM) of thoracic esophageal squamouscellcarcinoma (ESCC) so as to provide reference basis for the clinical prevention and treatment of LNM of thoracic ESCC. Methods: Through a retrospective analysis on the clinical and follow-up data collected from 96 patients with LNM of thoracic ESCC admitted in our hospital from 1 February 2008 to 1 March 2012, this study described clinical characteristics of these patients. Meanwhile, Cox proportional hazard regressive model was used to investigate factors influencing the prognosis of patients with LNM of thoracic ESCC. Results: 121 patients with LNM of thoracic ESCC accounted for 39.0% of ESCC patients (121/310) in the same period. During operation, a total of 2531 lymph nodes were dissected. 312 were found to be positive nodes in postoperative pathological diagnosis. The rate of lymphatic metastasis was 12.3%. For 57.9% (70/121) patients, the carcinoma metastasized to ≥ 3 nodes. For 28.9% (35/121) patients, LNM involved ≥ 2 areas. Among these cases, there were 33 patients with neck lymphatic metastasis (19.1%), 90 patients with thoracic lymphatic metas- tasis (52.0%) and 50 patients with abdominal lymphatic metastasis (28.9%). The median survival time of patients with LNM of thoracic ESCC postoperation was 35 months with a 1-, 3- and 5-year survival rate of 80.2%, 48.8% and 21.5%, respectively. Univariate analysis showed that there was statistically significant difference (P < 0.05) in terms of postoperative survival condition for patients with LNM of thoracic ESCC of different sex, length, degree of differentiation and invasion depth of tumor, blood vessel invasion, with different number of nodes and areas involved, as well as rate of lymphatic metastasis (%). Multivariate Cox regression analysis indicated that poorly dif- ferentiated esophageal carcinoma (HR = 2.14, 95% CI: 1.08-4.26), depth of invasion in T3/T4 (HR = 1.87, 95% CI: 1.02-3.45), rate of lymphatic metastasis > 20% (HR = 3.07, 95% CI: 1.72-5.47) and areas involved ≥ 2 (HR = 2.60, 95% CI: 1.44-4.70) were factors influencing the prognosis of patients with LNM of thoracic ESCC. Conclusion: The prognosis of patients with LNM of thoracic ESCC is poor. In particular, the prognosis of patients with LNM of thoracic ESCC combined with poorly differentiated esophageal carcinoma, depth of invasion in T3/T4, high rate of lymphatic metastasis and multiple areas involved is poor. Comprehensive treatment measures should be taken to prolong patients’ survival time and improve their quality of life.
Background: Neuroendocrine cellcarcinoma is a rare variant of esophageal carcinoma. The characteristic clinical features and diagnosis of superficial neuroendocrine cellcarcinoma remain to be established. We report a rare case of superficial coexistence of neuroendocrine cellcarcinoma with squamouscellcarcinoma treated by endoscopic submucosal dissection, and regional lymphnodemetastasis was detected after additional surgical treatment. Case presentation: A 77-year-old Japanese man with esophageal squamouscellcarcinoma received endoscopic submucosal dissection in en-bloc resection. Histopathological findings showed that lymphovascular invasion by the neuroendocrine cellcarcinoma component occurred in the deep part of the muscularis mucosa. Regional lymphnodemetastasis was identified after additional surgical treatment. After surgical treatment, our patient received chemotherapy consisting of etoposide and carboplatin for 3 months. He is alive and shows no sign of disease recurrence 12 months after surgery.
VM in tumors plays an important role in tumor aggres- sion . We also found VM is more common in the advanced stage of LSCC than in the primary stage. How- ever, these results are different than the observations from a breast cancer study by Shirakawa et al, which showed that the VM group did not exhibit a more advanced pTNM stage than the non-VM group. However, there was no difference of VM exhibition among different T stage founded in Shirakawa's and our studies. We sug- gested that the discrepancy result may due to different influence of VM on local lymphnodemetastasis or dis- tant metastasis in diversity tumors. Therefore, the impact of VM on the survival of patients with LSCC needs to be confirmed further by some international collaboration of studies and systematic reviews by meta-analysis.
Esophageal cancer is the seventh most preva- lent malignant cancer and the sixth chief cause of cancer death worldwide . For the fast pro- gression and late stage in diagnosis, the prog- nosis of esophageal cancer is dismal. The tumor-node-metastasis (TNM) staging system has made great contributions to the selection of treatment strategies, as well as prediction of prognosis. However, the fact that patients with similar cancer stages tend to have discrepan- cies in their prognosis indicates that TNM sys- tem alone is far from meeting the clinical needs. Some esophageal cancer patients with early stage receiving radical surgery and adjuvant therapy may die of distal metastasis. Thus, it is necessary for us to find new biomarkers to pre- dict the prognosis and provide more informa- tion for treatment strategies.
Approximately 130,000 new cases of laryngeal cancer are diagnosed worldwide each year, and over 95% of these diagnoses are laryngeal squamouscell carcinomas (LSCC) . Despite improved diagnostic methods and therapies, the cure rate of LSCC has only marginally improved over the past decade . A main chal- lenge is the lack of accurate and reliable meth- ods for early diagnosis. Traditional methods, such as physical examination, ultrasound, and computer tomography, are often insufficient for early detection . In contrast to these stan- dard clinical methods, molecular techniques used to measure metabolic activity of cancer cells may provide more sensitive and accurate detection for patients. Such methods may also help identify new therapeutic targets for LSCC . Although the best-known risk factors for LSCC, clinical TNM staging and histopathologi- cal grading, will retain their usefulness, the identification of molecular biomarkers may pro- vide additional information for stratifying pa-
Future significance: There is a list of serious injuries and death in which one or more subjects of selfie were killed or injured, either before, during or after having taken a photo of themselves, with the accident at least in part attributed to the taking of the photo. The selfie craze doesn’t seem to be dying anytime soon. But a lot of people are dying because of it. In fact, India led the world in selfie-related deaths in 2015. In the current technological world, it is has been very important for the mental health professionals to explore how an individuals are using selfies, social media as an important part of a mental health assessment of the surrounded people. As it will increase the mode of discussion about the self-esteem and the safe use of technologies. Various attempts should be made by the professionals, societies and families to reduce the electronic overload to regain the healthy balance of life, work and technology in the daily living. Future research ideas include conducting the same study on a larger sample size to see if the results will vary or remain the same. Another future research topic will be to study the effects of selfies on self-esteem. The researcher would like to find out whether or not selfies have the power to increase the levels of self-esteem.
In normal physiological functions, homeostatic chemokines regulate the migration of leukocytes by recruiting specific populations of lymphoid cells to certain tissues in either innate or acquired immune responses. For instance, chemokine ligand CCL27 induces migration of leukocyte antigen CLA+ T cells which express chemokine receptor CCR10 to the skin , and ligand CXCL12 in the bone marrow recruits hematopoietic stem cells which express the receptor CXCR4 . While chemokines normally regulate the migration of immune cells, other cell types can take advantage of these chemokine “pathways” by expressing the appropriate receptor. Recent studies suggest that metastatic cancer cells simply co-opt these chemokine pathways to migrate to distant sites. Like normal leukocyte migration, tumor cellmetastasis requires passage through vascular barriers, entry into the circulation, and extravasation at distant, non-random, organ-specific locations. Since leukocyte trafficking is regulated by chemokine receptors and their ligands, chemokines may also play a key role in initiating and regulating tumor cell migration and metastasis.
From our patients, 22 presented lymphnodemetastasis. The high incidence of metastasis in this selected group, confirms that tumors greater than 5 cm or invasive to soft tissue or bones (T3 and T4) are high risk for lymphatic spread. The 11 patients with metastasis at presentation, also reflects possible referral bias to tertiary cancer center and is similar to other reports [10,15]. Comparative sur- vival demonstrates that more advanced tumors (T4) had worse prognosis with poor outcome. This was expected and confirms the value of T stage from the TNM classifica- tion as a prognostic tool. The diagnosis of lymphnodemetastasis during follow-up in N0 patients occurred in 24.4% of cases. This information would be enough for indication of elective lymphadenectomy or sentinel node dissection in most tumors. However, survival analysis among patients without initial lymphnodemetastasis (N0), showed no difference considering those who devel- Overall survival for T3 and T4 patients
Notes: (A) Merkel cellcarcinoma was excised from the right preauricular area. (B) H&e staining revealed diffuse proliferation of atypical and pleomorphic tumor cells; small, round basophilic cells are arranged in cordlike structures (original magnification ×200). Histology of the tumor. (C–G) Immunohistochemical analysis found that the tumor cells were positive for (C) CK20, (D) syn, (E) Cga, (F) CD56 and (G) Ki67 (original magnification ×400). (H, I) excisional biopsy revealed Merkel cellcarcinoma with negative margins (original magnification: H ×40; I ×200).
Blocks of LNM, normal lymph nodes from the patient and inoculated tumors from SCID mice were fixed in 10% formalin for 24 hours, embedded in paraffin, and then cut into 3-μm tissue sections. The sections were then affixed to slides, deparaffinized, rehydrated through graded alcohols, heated in a microwave oven on high power and medium power for 10 min in 10 mM EDTA (pH 9.0) for antigen retrieval, incubated in 3% H 2 O 2 for 10 min to inactivate endogenous peroxidase, and incubated in 5% BSA for 40 min. After blocking, the tissue sections were incubated with primary antibodies overnight at 4°C, followed by the addition of secondary antibodies and incubation in the dark for 1 hour at 37 °C. For tissue slides, a SignalStain® 3,3 N-Diaminobenzidine (DAB) Tertrahydrochloride Substrate Kit was used after incubation with secondary antibodies to visualize target proteins, and Van-Hematoxylin hematoxylin stain (Harris) was used for counterstaining. Observation and image acquisition were performed using a NIKON ECLIPSE 80i advanced research microscope. Primary antibodies against pan-CK, Vimentin, CK 5, desmoplakin, HPV16 E6/18 E6, p16 (Santa Cruz, USA), p53 rabbit mAb (Cell Signaling Technology, USA), and EGFR (Santa Cruz, USA) were used. The secondary antibodies included peroxidase- conjugated goat anti-mouse (Boster, China).
De ﬁ nitions of several predictors were recorded as pre- viously published. 21 Clinically positive inguinal lymph nodes (cN+) were de ﬁ ned as those that are palpable or visible with imaging examinations. Histological grade was divided into three groups: G1 (well-differentiated), G2 (moderately differentiated), and G3 (poorly differentiated). There were two TNM systems, including the American Joint Commission on Cancer (AJCC) and the Union for International Cancer Control (UICC). Both of them had several versions. We de ﬁ ned T2 and greater stage as higher stage. Growth pattern was classi ﬁ ed as super ﬁ cial or vertical; Invasion depth was measured from the intact basement membrane at the edge of the primary tumor to the deepest in ﬁ ltrating tumor cell. LVI was de ﬁ ned as the presence of cancer embolus in the lymphatic or vascular lumen that was detected by immunohistochemical stain- ing. Histopathological subtypes were classi ﬁ ed as low risk (verrucous, papillary, and warty), intermediate risk (usual SCCs and mixed forms), and high risk (basaloid, sarco- matoid, adenosquamous, and poorly differentiated types) according to the European Association of Urology (EAU) guidelines. 4 PD-L1, Ki-67, P53 protein, and HPV virus were measured in tumor. SCC-Ag, NLR, and CRP were measured in serum.
Thickness has now become the major prognosticator in melanoma, largely determining initial treatment. Depth of penetration in millimeters has been found to be a most valuable measurement in predicting tumor behavior in cancers of the uterus, especially the cervix, cancers of the gastrointestinal tract, especially the colorectum, and cancers of the bladder. Caution is appropriate in comparing thickness with surface size, because no doubt exists that, in cancer generally, very small is good and very large is bad. Tiny oral cancers with a surface diameter of around 10 mm are associated with few if any node metastases and have a very good prognosis. Conversely, very large extensive cancers involving adjacent structures can seldom be cured. Caution is needed also because depth of penetration and thickness are subtly different; depth is not always reproducible in the mouth. The presence of micro metastasis is thought to correlate with conventional factors such as the size of the tumor and thickness of the tumor . Thick tumors, which invade more deeply, have access to wider lymphatics in which tumor emboli can form more readily than in the small-caliber lymphatics of superficial areas. So tumor thickness is one of the best predictor for loco- regional metastasis and recurrence.