Head and Neck Primary Mucosal Melanoma: Report of 17 Cases

Introduction: Mucosal melanoma (MM) is a rare disease, accounting for 1.7% - 3% of all melanomas and 8% of all head and neck melanomas. It’s a rare cancer with a very poor prognosis. Materials and Methods: We retrospectively reviewed the records of 17 patients with primary mucosal melanomas of the head and neck who were diagnosed between January 2007 and December 2012. Results: Our patient population included 9 women and 8 men. The age ranged from 61 to 75 years. The primary site of disease was in the sinonasal cavity for 12 patients (70%) and oral cavity for 5 patients. Treatment modalities for mucosal melanoma include surgical resection with or without neck dissection, immunochemotherapy, and radiation therapy (RT). 15 patients had attempted curative resections. Two patients received palliative radiation therapy as the primary treatment and chemotherapy as the adjuvant treatment. Discussion: Primary mucosal melanoma is a rare cancer and represents only 1.7% - 3% of all primary melanomas [1]-[3]. Mucosal melanoma must always be considered for multimodality therapy: surgical excision, medical oncology, and radiation therapy. Despite its radioresistant nature of tumor, the role of radiation therapy following surgical intervention has typically been advocated.

E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome

瞄准：调查在颜色在转移的进程期间发生在 E-cadherin 表示的变化表面的癌症。方法：E-cadherin 表示被免疫组织化学检测，表示的二个索引是计算的它反映了表示和地点(膜和细胞质) 的水平。Univariate 并且多，变量幸存分析被用来作为两个的预言者估计这二个 E-cadherin 索引的价值没有疾病(DFS ) 并且疾病特定(决策支持系统) 幸存。结果：E-cadherin 膜索引(MI ) ，然而并非细胞质的索引(CI ) ，比他们的转移在原发性瘤是显著地更高的(P = 0.0001 ) 。而且，原发性瘤 MI 和 CI 在开发了随后的转移的病人之中是更高的(P = 0.022 并且 P = 0.007，分别地) 。有趣地，两个索引在与另外的解剖地点相比的肝转移是更高的(MI， P = 0.034 并且 CI， P = 0.022 ) 。原发性瘤的 CI 是 DFS 的一个重要预言者(P = 0.042， univariate 分析) ，与在 CI 和 DFS 之间的强壮的反的关联(P = 0.006，多变量分析) 。最后，原发性瘤的 MI 证明了是决策支持系统的一个重要独立预言者，与与更有利的结果被联系的更高的索引(P = 0.016 ) 。结论：在颜色的 E-cadherin 表示和分发的检查表面的肿瘤能在预言是极其珍贵的疾病复发。E-cadherin 的异常细胞质的表示能预言疾病复发为病人和临床医生显然是很重要的，并且显著地有关病人的治疗和管理影响决定的观察。

Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence

AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer. METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT, n = 90), long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with immunohistochemistry for CD44v6. The extent and intensity of membranous and cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern, were analyzed.RESULTS: Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous CD44v6 expression, the staining pattern in the invasive front was determined as "front-positive" and in 41% as "front-negative". The latter pattern was associated with narrower circumferential margin (P = 0.01), infiltrative growth pattern (P < 0.001), and shorter disease-free survival in univariate survival analysis (P = 0.022) when compared to the "front-positive" tumors. CONCLUSION: The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease.

Technological advances in radiotherapy for esophageal cancer

Radiotherapy with concurrent chemotherapy and surgery represent the main treatment modalities in esophageal cancer.The goal of modern radiotherapy approaches,based on recent technological advances,is to minimize post-treatment complications by improving the gross tumor volume definition (positron emission tomography-based planning),reducing interfraction motion (image-guided radiotherapy) and intrafraction motion (respiratory-gated radiotherapy),and by better dose delivery to the precisely defined planning target volume (intensity-modulated radiotherapy and proton therapy).Reduction of radiotherapy-related toxicity is fundamental to the improvement of clinical results in esophageal cancer,although the dose escalation concept is controversial.

Toremifene in the treatment of breast cancer

Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier(SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase Ⅲ trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events andit has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.

Cyclooxygenase-2 expression as a predictor of outcome in colorectal carcinoma

AIM:To correlate cyclooxygenase-2(COX-2)expression profile with clinical and pathological variables to assess their prognostic/predictive value in colorectal carcinoma(CRC).METHODS:Archival tumor samples were analyzed using immunohistochemistry for COX-2 expression in 94 patients with CRC.Patients were diagnosed and treatedat the Departments of Surgery and Oncology,King Abdulaziz University Hospital,Saudi Arabia.RESULTS:Fifty-six percent of the tumors showed positive cytoplasmic COX-2 expression,whereas 44%of cases were completely COX-2-negative.There were no significant correlations between COX-2 expression and sex,age,grade or tumor location.However,COX-2 expression revealed a significant correlation with tumor stage(P=0.01)and distant metastasis(P=0.02),and a borderline association with lymph node involvement(P =0.07).Tumors with high COX-2 expression showed a higher recurrence rate than tumors with no expression(P<0.009).In univariate Kaplan-Meier survival analysis,there was a significant(P=0.026)difference in disease-free survival between COX-2-positive and negative tumors in favor of the latter.COX-2 expression did not significantly predict disease-specific survival,which was much shorter for COX-2-positive tumors.In multivariate(COX)models,COX-2 did not appear among the independent predictors of disease-free survival or disease-specific survival.CONCLUSION:COX-2 expression seems to provide useful prognostic information in CRC,while predicting the patients at high risk for recurrent disease.

Up-regulation of α-catenin is associated with increased lymph node involvement in colorectal cancer

AIM: To investigate the changing pattern of α-catenin expression and its relationship to clinical and pathological features of colorectal cancer (CRC) patients. METHODS: Archival tumor samples were analyzed using immunohistochemistry (IHC) for α-catenin in 91 patients with advanced CRC. RESULTS: The values of α-catenin membrane index (MI) and cytoplasmic index (CI) were significantly related to the depth of tumor invasion (P = 0.027, P = 0.020, respectively), high indices being associated with increased depth of the primary tumor invasion (T3 and T4). Similarly, patients with high α-catenin expression had a signifi cantly increased risk of lymph node metastasis (32/39 vs 37/52 for MI and 37/45 vs 32/46 for CI) (P = 0.001, P = 0.0001, respectively, for LNN status). An altered expression (i.e., cytoplasmic pattern) was also related (P = 0.047) to the response to chemotherapy; patients with low CI were more responsive (CR: 7/46) than patients with high CI values (CR: 0/45). There was a marginal effect on survival in patients time with metastases (SWM) (P = 0.087); patients with low CI showing slightly longerSWM, but no such effect on disease free survival (DFS) or disease specifi c survival (DSS). As to co-expression with another member of the adhesion complex (β-catenin), high α-catenin/β-catenin MI index was of marginal signifi cance in predicting longer DSS (P = 0.063, log-rank). CONCLUSION: The results implicate that high α-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in CRC.

Dynamics of genital human papillomavirus （HPV） nfections among males eventually being uncovered

Studies addressing the type-specific outcomes of cervical human papillomavirus （HPV） infections in women started emerging since the early 2000s, resulting in prolific lit- erature and more profound understanding of the dynamic nature of these viral outcomes （incident infections,

Systemic therapy for cervical carcinoma–current status

Two major treatment modalities in cervical cancer are radiation therapy（RT） and surgery. Chemotherapy continues to be the main form of systemic therapy adjunctive to definitive local therapies, and is used for palliation.Platinum-based regimens, administered concurrently with both definitive and postoperative RT, were demonstrated to provide significant survival benefits, whereas the beneficial effect of concurrent chemoradiotherapy in later-stage disease was smaller. The role of chemotherapy in addition to RT in IB1/IIA1 cervical cancer patients not undergoing surgery remains undefined. Likewise, the role of chemotherapy in combination with postoperative RT for patients with intermediate-risk factors for recurrence has not yet been verified. The recent standard for chemoradiotherapy is cisplatin alone administered weekly. Other cisplatin-based or non-cisplatin-based regimens have not been subjected to large clinical studies. The benefits of consolidation chemotherapy after chemoradiation for locally advanced cervical cancer are still undetermined. Neoadjuvant cisplatin-based chemotherapy followed by surgery has shown survival benefits, however its role in the era of chemoradiotherapy remains unclear. The combination of cisplatin and paclitaxel is considered a standard regimen in the palliative setting. There is no standard of care for second-line systemic therapy in advanced cervical cancer.Bevacizumab combined with palliative chemotherapy（cisplatin/paclitaxel or topotecan/paclitaxel） in the first-line treatment for recurrent/metastatic cervical cancer significantly improves overall survival when compared to chemotherapy alone. The role of immunotherapy in cervical cancer remains to be established. The optimal combined modality treatment including systemic therapy for cervical tumors of non-squamous histology remains a matter of debate. Ongoing accumulation of data on genomic and proteomic characteristics provides insight into the molecular heterogeneity of cervical cancer and paves the way for developing molecularly targeted therapies.

Increased proliferation activity measured by immunoreactive Ki67 is associated with survival improvement in rectal/recto sigmoid cancer

AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer.METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinicopathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1, 26 (17.8%) with T2, 94 (64.4%) with T3, and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically. Samples were divided according to mean value into high (＞40%) and low (≤40%) expression. Areas of extensive proliferation (＞50%) were defined as 'hot spot' areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P = 0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P＜0.001), presence of lymph node metastases (P = 0.015), age (P = 0.035) andpresence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.

Nuclear β-catenin expression as a prognostic factor in advanced colorectal carcinoma

AIM: To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer (CRC). METHODS: Archival tumor samples were analyzed for β-catenin using immunohistochemistry (IHC) in 95 patients with advanced CRC. RESULTS: Membranous β-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression,and 55 (58%) cases showed nuclear expression. In univariate (Kaplan-Meier) survival analysis,only the nuclear index (NI) was a signifi cant predictor of disease-free survival (DFS) (P = 0.023; n = 35),with a NI above the median associated with longer DFS (34.2 mo) than those with a NI below the median (15.5 mo) (P = 0.045,ANOVA). The other indices were not significant predictors of DFS,and none of the three tested indices (for membranous,cytoplasmic,or nuclear expression) predicted disease-specific survival (DSS). However,when dichotomized as positive or negative nuclear expression,the former was a signifi cant predictor of more favorable DFS (P = 0.041) and DSS (P = 0.046). CONCLUSION: Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.

Moving forward in colorectal cancer research, what proteomics has to tell

Colorectal cancer is the third most common cancer and is highly fatal. During the last several years, research has been primarily based on the study of expression profiles using microarray technology. But now, investigators are putting into practice proteomic analyses of cancer tissues and cells to identify new diagnostic or therapeutic biomarkers for this cancer. Because the proteome reflects the state of a cell, tissue or organism more accurately, much is expected from proteomics to yield better tumor markers for disease diagnosis and therapy monitoring. This review summarizes the most relevant applications of proteomics the biomarker discovery for colorectal cancer.

Bcl-2 expression significantly correlates with thymidylate synthase expression in colorectal cancer patients

AIM: To examine the expression of thymidylate synthase (TS) and oncoprotein Bcl-2 in advanced colorectal cancer (CRC) patients,and to determine their mutual relationship,association to therapeutic response and impact on disease outcome.METHODS: Tumor samples from 67 patients with CRC,who were treated at advanced stage with either irinotecan alone or in combination with 5-fluorouracil/ leucovorin,were analyzed for expression of TS and Bcl-2 using immunohistochemistry.RESULTS: A significant linear correlation between lower expression levels of Bcl-2 and lower levels of TS expression was found (P = 0.033).Patients with high levels of both TS and Bcl-2 expression had a significantly longer disease-free survival (DFS) (42.6 mo vs 5.4 mo,n = 25) than those with low TS/Bcl-2 index (P = 0.001).Tumors with low levels of both TS and Bcl-2 were associated with a longer survival with metastasis (WMS) interval in the whole patients group (n = 67,P = 0.035).TS/Bcl-2 index was not significantly related to disease-specific survival.CONCLUSION: The present data suggest that CRC patients with low TS/Bcl-2 demonstrate a significantly shorter DFS and longer WMS.

低辐射剂量下乳腺CT高对比度的实现

本研究经当地伦理委员会批准,所有病人均知情同意。研究的目的是证明高空间分辨力低剂量CT与乳腺钼靶片及常规CT相比能明显提高乳腺的影像对比度。

Current challenges in applying gene-driven therapies in clinical lung cancer practice

Over the last twenty years,with the development of gene-driven therapies,numerous new drugs have entered clinical use.Very few of these new drugs are suitable for a large number of patients,and all require molecular genetic testing.In lung cancer,gene-targeted therapy has evolved rapidly and has placed demands on the development of diagnostics and tissue sample preparation and logistics.Rapid diagnosis and prevalence assessment are necessary to determine the prognosis of a lung cancer patient based on the latest research findings.Therefore,the molecular-genetic diagnostic pathway must also be accelerated and matured to do the necessary analyses on small samples.Because lung cancer rebiopsy can be difficult,liquid biopsy techniques should be developed to cover more of the treatable mutations.There are obstacles related to tissue sampling,new genomic techniques and access to gene-driven cancer drugs,including their affordability.With this review and case study,we go into the obstacles faced by our clinic and discuss how to tackle these obstacles in lung cancer.We use lung cancer as an example due to its complexity,though these same obstacles are found in different cancers on a minor scale.

Platelet RNA enables accurate detection of ovarian cancer:an intercontinental,biomarker identification study

Platelets are reprogrammed by cancer via a process called education,which favors cancer development.The transcriptional profile of tumor-educated platelets(TEPs)is skewed and therefore practicable for cancer detection.This intercontinental,hospital-based,diagnostic study included 761 treatment-naive inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers(China,n=3;Netherlands,n=5;Poland,n=1)between September 2016 and May 2019.The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese(VC1 and VC2)and the European(VC3)validation cohorts collectively and independently.Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets.The AUCs for TEPs in the combined validation cohort,VC1,VC2,and VC3 were 0.918(95%CI 0.889-0.948),0.923(0.855-0.990),0.918(0.872-0.963),and 0.887(0.813-0.960),respectively.Combination of TEPs and CA125 demonstrated an AUC of 0.922(0.889-0.955)in the combined validation cohort;0.955(0.912-0.997)in VC1;0.939(0.901-0.977)in VC2;0.917(0.824-1.000)in VC3.For subgroup analysis,TEPs exhibited an AUC of o.858,0.859,and 0.920 to detect early-stage,borderline,non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis.TEPs had robustness,compatibility,and universality for preop.erative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities,heterogeneous histoiogical subtypes,and early-stage ovarian cancer.However,these observations warrant prospective validations in a larger population beforeclinicalutilities.

成人眼内恶性畸胎样髓上皮瘤的临床病例报道和文献回顾

Purpose: To report a case of intraocular medulloepithelioma, an embryonal tumour with extremely rare presentation in adults. Method: The case of a 44- year-old man with intraocular malignant teratoid medulloepithelioma, primarily diagnosed as intraocular teratoma, is described and the literature on this subject is reviewed. Results: The patient presented with progressive proptosis caused by a tumour in the left eyeball. He had a 28- year history of loss of vision in the left eye. Histopathological examination of the enucleated eye demonstrated an intraocular teratoma. No adjuvant treatment was given. Six months later the patient presented with massive progression in the left orbit and intracranial invasion. Cisplatin-based chemotherapy was administered, but discontinued after two cycles due to poor tolerance and lack of response. At subsequent pathology review, a final diagnosis of malignant teratoid medulloepithelioma was made. Salvage radiotherapy (60 Gyin 30 fractions) resulted in partial response of the intracranial lesion. However, the patient died 6 months later due to intracranial tumour progression. Conclusion: Medulloepithelioma should be considered in the differential diagnosis of intraocular tumours in adults, especially in the case of coexisting, longstanding ocular symptoms. In some cases this disease is very aggressive.

外照射治疗与大剂量近程放疗同时联合顺铂与紫杉醇化疗治疗晚期宫颈癌

Objective. The aim of the present study was to evaluate toxicity and efficacy of concurrent chemoradiation with cisplatin and paclitaxel and high-dose rate (HDR) brachytherapy in patients with locally advanced cervical cancer. Patients and methods. 19 patients with locally advanced cervical carcinoma were treated with external beam radiotherapy (EBRT) to the pelvis ±para-aortic nodes, HDR brachytherapy, cisplatin at doses of 50 mg/m2 in weeks 1 and 4, and weekly paclitaxel at 50 mg/m2 in weeks 1-5 during years 2000-2002. Chemotherapy was administered until leukopenia ≤2500/mm3, thrombocytopenia < 100,000/mm3, and/or hemoglobin level < 100 g/l occurred. The median follow up was 36 months (range 25-47). Results. Only four patients were able to tolerate the complete intended course of radiochemotherapy. Chemotherapy was stopped in two patients because of allergic reaction and in one patient because of deep thrombosis. In 12 other cases, chemotherapy was discontinued for hematological toxicity. The 3-year disease free survival was 66%, the 3-year overall survival was 74%. Conclusion. The hematological toxicity was the main factor limiting administration of cisplatin at 50 mg/m2 in weeks 1 and 4 and weekly paclitaxel at 50 mg/m2 in weeks 1-5 concomitantly with extended field radiotherapy of locally advanced cervical carcinoma.

乳腺X线筛查及其他方法检出的乳腺癌发生远期复发的危险

背景：对确诊患乳腺癌的妇女行全身辅助治疗是基于其肿瘤复发的危险。进行危险评估时，通过乳腺X线筛查发现的肿瘤发生复发的危险与其他方法发现的大小相似的肿瘤相同。目的：对乳腺X线筛查或其他方法发现的女性乳腺癌患者的复发危险和生存率进行比较。设计、地点及患者：对乳腺X线筛查出的肿瘤和其他方法发现的肿瘤进行回顾性研究，比较其临床、组织病理学和生物学特性。从芬兰肿瘤登记处（Finnish Cancer Registry）检出1991年或1992年诊断患有乳腺癌的妇女（n=2842）。中位随访时间为9．5年。应用免疫组织化学或原位杂交法对肿瘤的生物学特性进行肿瘤组织微矩阵分析，包括ERBB2、TP53、MK167表达和ERBB2扩增数据。主要观察指标：影响乳腺癌远期复发和10年生存率的潜在危险因素的单变量分析和多变量分析。结果：在1983例患单侧浸润性乳腺癌的妇女中，1918例有肿瘤直径数据。通过乳腺X线筛查发现的肿瘤患者与其他方法发现的肿瘤患者比较，前者10年远期无病生存率更高（肿瘤≤10mm[n=386]：92％比85％[P=0．04]；肿瘤11～20mm[n=808]：88％比76％[P〈0．001]；肿瘤21～30mm[n=409]：86％比63％[P=0．008]；肿瘤〉30mm[n=315]：68％比50％[P=0．12]）。在包括各种肿瘤生物学因素的Cox多变量模型中，其他方法发现的肿瘤患者发生远期复发的相对风险比（hazard ratio[HR]，1．90；95％可信区间，1．15—3．11）显著高于乳腺X线筛查发现的肿瘤患者（P=0．01）。通过乳腺X线筛查确诊乳腺癌是降低远期复发相对HR的独立预后变量。这种作用相当于甚至超过肿瘤直径缩少1cm的作用（HR，1．20；95％可信区间，1．10～1．31）。结论：通过乳腺X线筛查发现的肿瘤与其他方法发现的大小相似的肿瘤比较，前者预后更好。在评估远期转移危险时必须考虑肿瘤检测方法，否则就会高估经乳腺X线筛查确诊的肿瘤患者发生远期转移的危险。