Prognostic Implications of Mucinous Differentiation in Metastatic Colorectal Carcinoma Can Be Explained by Distinct Molecular and Clinicopathologic Characteristics

Background

The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remains poorly characterized. The present study characterized the baseline characteristics, mutational profile, and clinical outcomes of patients diagnosed with mucinous CRC.

41例宫颈粘液腺癌临床分析

目的：探讨宫颈粘液腺癌的临床特点及其治疗方法。方法：本文对1958年至1990年我院收治的41例宫颈粘液腺癌的临床资料进行回顾性分析。结果：宫颈粘液腺癌占同期宫颈腺癌的19．16（41／214）。平均年龄为50．89岁，阴道白带增多为临床突出症状，按FIGO分期，Ⅱ期占34．14％（14／41），Ⅲ期占56．09％（23／41），Ⅳ期占9．76％（4／41）。采用单纯放疗26例，综合治疗15例。总5年生存率为13．20％，其中Ⅱ期33.30％，Ⅲ期2．17％，Ⅳ期0.宫颈直径≤3cm和＞3cm5年生存率分别为9．09％和12.80％（P＞0．05）。结论：本资料表明宫颈粘液腺癌的预后比宫颈鳞癌以及其他类型的宫颈腺癌差，与临床分期有关，但与宫颈肿瘤大小无关。     

胃粘液腺癌149例临床病理学特点

目的: 比较胃粘液腺癌(Mucinous gastric carcinoma,MGC)不同分期的临床病理学差异,探讨影响MGC预后的临床病理学特征。 方法: 分析1982年1月～1997年12月收治的MGC患者149例的临床病理及其预后。 结果: MGC更易发生浆膜浸润(Ⅲ、Ⅳ期S₂+S₃:67.5%);浸润性更强(Ⅰ+Ⅱ期T₃:6.2%;Ⅲ+Ⅳ期T₃:44.4%);中晚期更易腹膜种植(P₂+P₃:30.7%);中晚期更易发生淋巴结转移(N₁+N₂:80.3%);根治性切除率早期明显高于中晚期(P<0.005);Ⅰ+Ⅱ期5年生存率早期明显提高(53.1%),中晚期仅为13.7%,两者之间比较有明显差别(P<0.005)。 结论: 不同时期MGC临床生物学行为不尽相同,其预后不良的原因与确诊时病期晚,发生浆膜浸润率、淋巴结转移率、腹膜播散率高和根治性切除率低有关。     

Prognostic Value of NRAS Gene for Survival of Colorectal Cancer Patients: A Systematic Review and Meta-Analysis

Introduction: NRAS gene is associated with malignant proliferation and metastasis of colorectal cancer (CRC).But its prognostic value on CRC is still unknown. The objective of this study is to perform a meta-analysis to obtainits prognostic value on survival of CRC patients. Methods: The systematic review and meta-analysis was designed,undertaken and reported using items from the PRISMA statement. Relevant articles were identified through PubMed(containing Medline), Embase, Web of Science databases and Google scholar search engines from their inception up toOctober 3, 2016. The articles about NRAS on prognosis of CRC patients were enrolled. The association between NRASand CRC survival time (including overall survival [OS], progression-free survival [PFS], and disease-free survival[DFS]) was evaluated using hazard ratio (HR) with its corresponding 95% confidence interval (CI). Results: A totalof fifteen articles were included. High-expression of NRAS was significantly associated with poor OS (HR: 1.36, 95%CI: 1.15–1.61), and poor PFS (HR: 1.75, 95% CI: 1.04–2.94). The combined HR of NRAS on DFS was 0.87 (95% CI:0.37–2.03). Subgroup analysis showed that NRAS was significantly associated with poor OS for patients from Westerncountries (HR: 1.38, 95% CI: 1.09–1.73), but not for those from Asian countries. Conclusions: This meta-analysisdemonstrate that NRAS gene could predict the poor prognosis for the CRC patients. More large-sample cohort studiesare needed to further confirm this conclusion.     

Prognostic Significance of Beclin-1 Expression in Colorectal Cancer: a Meta-analysis

Objective: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers.However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed toevaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients.Materials and Methods: All related studies were systematically searched in Pubmed, Embase, Springer andChinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed todetermine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were includedin our analysis. Results: Our data showed that high Beclin-1 expression in patients with CRC was associatedwith poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overallsurvival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was noevidence of publication bias as suggested by Egger’s tests for tumor distant metastasis (p=1.000), differentiation(p=1.000) and OS (p=0.308). Conclusions: Our present meta-analysis indicated that elevated Beclin-1 expressioniss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as anefficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.     

结肠黏液腺癌临床病理特征分析

目的：探讨结肠黏液腺癌的临床病理特征及预后特点。方法回顾性分析672例初治的接受根治性手术的结肠癌患者,其中黏液腺癌为41例,非黏液腺癌为631例,比较两者临床病理特征和复发方式。结果黏液腺癌患者比非黏液腺癌患者更年轻（<50岁比例：48.8豫 vs 31.4豫,P <0.05）,肿瘤直径更大（6.0 cm vs 4.5 cm,P <0.05）,更多位于右半结肠（右半结肠比例：44.0豫 vs 17.3豫,P <0.05）和病理 T 分期更高（T3、T4比例：90.2豫 vs 72.7豫,P <0.05）,3 a 生存率更短（39.2豫 vs 68.5豫,P <0.05）。复发情况中,黏液腺癌腹膜转移率比非黏液腺癌更高（57.1豫 vs 1.5豫,P <0.05）。结论与非黏液腺癌比较,结肠黏液腺癌发病年龄更年轻,更多处于晚期和右半结肠,腹膜转移可能性更大,治疗预后更差,提示结肠黏液腺癌患者需要特异的治疗方案。     

370 例肺腺癌各亚型间临床及预后影响因素的比较

目的：根据WHO2004年对于肺腺癌分型的最新定义标准,探讨肺腺癌各亚型之间预后的差异及预后因素。方法：收集本院2000年1 月至2003年12月期间行手术治疗的370 例肺腺癌患者病理切片,并对其临床资料进行回顾性分析,对患者的生存时间进行随访;采用Kaplan-Meier 法计算生存率,采用COX 模型进行多因素分析。结果：全组患者术后5 年总体生存率25.26% ,中位生存期3.89年;单因素分析结果显示：病理亚型、支气管断端是否阳性、肿瘤直径、TNM分期、T 分期、N 分期、术后是否行化疗、免疫治疗对全组患者总体生存率的影响有统计学意义;多因素分析显示：术后病理亚型、气管断端是否阳性,TNM分期、肿瘤直径、是否行化疗为影响患者总体生存率的独立因素。各亚型之间分析显示：单纯型细支气管肺泡癌（Bronchioloalveolarcarcinoma ,BAC ）的5 年生存率为41.30% ,优于其它类型腺癌（P=0.002）;无BAC 成份的各亚型腺癌的预后差异无统计学意义;含BAC 的混合型腺癌预后介于前两者之间。结论：手术仍为肺腺癌的主要治疗手段;含BAC 的混合型腺癌预后介于BAC 与无BAC 成份的其他类型腺癌,可视为独立的病理类型;术后病理亚型、气管断端是否阳性,TNM分期、肿瘤直径、化疗为影响患者总体生存率的独立因素。     

Lack of Benefit From Anti-EGFR Treatment in RAS and BRAF Wild-type Metastatic Colorectal Cancer With Mucinous Histology or Mucinous Component

BackgroundAdenocarcinoma with mucinous histology or mucinous component are histologic subtypes of metastatic colorectal cancers (mCRCs) with limited benefit from cytotoxic agents. Their sensitivity to anti-epithelial growth factor receptors (EGFRs) is not clear.Patients and MethodsThe activity and efficacy of anti-EGFRs was retrospectively evaluated among patients with RAS and BRAF wild-type mCRC with or without mucinous histology or mucinous component. Subgroup analyses according to primary tumor location were conducted.ResultsOverall, the study population included 22 mucinous or with mucinous component tumors (11 right- and 11 left-sided tumors) and 83 not mucinous tumors. One patient experienced partial response among mucinous tumors, whereas in the not mucinous group, 42 patients experienced partial response, with an overall response rate of 4% and 51%, respectively (P = .003). The median progression-free survival was 2.8 versus 6.7 months (hazard ratio, 0.28; 95% confidence interval, 0.13-0.59; P < .001), and the median overall survival was 6.5 and 16.7 months (hazard ratio, 0.58; 95% confidence interval, 0.33-1.00; P = .022), for the mucinous and not mucinous groups, respectively. Similar results were observed in subgroup analysis according to primary tumor location.ConclusionAnti-EGFRs may not provide clinically meaningful benefit in mCRCs with mucinous histology or mucinous component compared with those without mucinous component, irrespective of sidedness.     

61例肺实性型腺癌的临床特征及预后分析

探讨肺实性型腺癌的临床特征及影响预后的因素。方法：回顾性分析1975年7月至2010年4月收治的61例肺实性型腺癌患者的临床资料,其中行手术为主的综合治疗54例、非手术治疗7例。分别对性别、年龄、吸烟史、肿瘤部位、肿瘤大小、淋巴结转移、pTNM分期等因素进行预后分析。Kaplan-Meier法计算生存率,Log-rank法进行生存率显著性检验,Cox比例风险回归模型进行单因素和多因素分析,评价各因素对预后的影响。结果：全部患者的1、3和5年生存率分别为77.3%、44.8%和25.2%。单因素分析显示：肿瘤大小（P<0.001）、有无淋巴结转移（P=0.014）、M分期（P=0.013）、pTNM分期（P=0.006）、治疗方式（P<0.001）和手术方式（P=0.006）是影响预后的因素。多因素分析显示：肿瘤大小（P=0.015）、有无淋巴结转移（P<0.001）、M分期（P=0.013）和治疗方式是影响预后的独立因素。结论：肺实性型腺癌发生率低,缺乏特异性临床表征,较易发生淋巴结转移,预后差。影响其预后的因素主要为肿瘤大小、淋巴结转移、M分期和治疗方式。根治性手术是其主要治疗手段。争取早期正确诊断、选择正确的治疗方法,是提高生存率的方法。     

Mucinous Cancer of the Appendix: Challenges in Diagnosis and Treatment

Abstract

The authors report and discuss a case of a mucinous carcinoma of the appendix, a rare entity with a distinct natural history that poses diagnostic and therapeutic challenges. Mucinous peritoneal carcinomatosis is most commonly associated with primary tumors of the appendix and colon. Typically, spread remains confined to the abdominal cavity. Imaging assessment of these mucinous lesions is difficult, while tumor markers (CEA and CA19.9) may be surrogates for extent of disease. Treatment consists of surgical debulking, sometimes coupled with intraperitoneal drug delivery, but recurrence is universal. New treatment approaches are needed. Mucin genes are regulated in part by epidermal growth factor receptor signaling. Therefore, we initiated a phase II study of cetuximab for mucinous peritoneal carcinomatosis, that was part of this patient's treatment.     

Mucinous Adenocarcinoma of the Thymus: A Case Report

A mucinous adenocarcinoma of the thymus is rare, and there is presently limited information on the clinical aspects of this uncommon type of tumor. Only six cases have been reported in the literature. A 49-year-old Japanese male presented with an anterior mediastinal mass, and underwent a tumor resection. Histologically the tumor consisted of a mucinous adenocarcinoma with pleural dissemination. Postoperative radiotherapy and chemotherapy were performed. The patient is still alive with pleural dissemination 11 months after surgery.     

Mucinous histology is associated with poor prognosis in locally advanced colorectal adenocarcinoma treated with postoperative first-line adjuvant chemotherapy: A systematic review and meta-analysis

PurposePostoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a peculiar histological subtype of CRC, but the prognosis of MAC patients is controversial. The objective of this study is to assess the implication of MAC in survival of patients treated with surgery and firs-line adjuvant chemotherapy.MethodsStudies describing outcomes for advanced MAC and non-specific adenocarcinoma (AC) of CRC patients treated with first-line postoperative adjuvant chemotherapy followed surgery were searched in PubMed, Embase, Medline, EBSCO, Wiley, and Cochrane Library (January 1963–August 2021). Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) for MAC to AC were extracted. Random-effects model was used for calculating the pooled HRs and 95% confidence interval (CI).ResultsThis meta-analysis is comprised of 8 studies involving a total of 124,303 CRC patients treated with first-line adjuvant chemotherapy followed surgery. The pooled HR for MAC was 1.23 (95% CI, 1.07–1.41, p < 0.01, I² = 80%), and the DFS (HR, 2.95, 95% CI, 1.22–7.14) of MAC patients were significantly poorer than AC patients. Similar results were also observed in stage III and FOLFOX regimen subgroups.ConclusionMAC was a risk factor for prognosis of localized advanced CRC patients treated with postoperative first-line adjuvant chemotherapy. Thus, the role of first-line adjuvant chemotherapy regimens should be further studied in these MAC patients.     

pT but not pN stage of the 8th TNM classification significantly improves prognostication in pancreatic ductal adenocarcinoma

The UICC TNM (tumour-node-metastasis) staging system for pancreatic ductal adenocarcinoma (PDAC) has been a matter of debate over decades because survival prediction based on T stages was weak and unreliable. To improve staging, the recently published 8th TNM edition (2016) introduced a conceptually completely changed strictly size-based T staging system and a refined N stage for PDAC. To investigate the clinical value of the novel TNM classification, we compared the prognostic impact of pT and pN stage between the 7th and 8th edition in two well-characterised independent German PDAC cohorts from different decades, including a total number of 523 patients. Former UICC T staging (7th edition 2009) resulted in a clustering of pT3 cases (72% and 85% of cases per cohort, respectively) and failed to show significant prognostic differences between the four stages in one of the investigated cohorts (p = 0.074). Application of the novel size-based T stage system resulted in a more equal distribution of cases between the four T categories with a predominance of pT2 tumours (65% and 60% of cases). The novel pT staging algorithm showed greatly improved discriminative power with highly significant overall differences between the four pT stages in both investigated cohorts in univariate and multivariate analyses (p < 0.001, each). In contrast, no prognostic differences were observed between the recently introduced pN1 and pN2 categories in both cohorts (p = 0.970 and p = 0.061).pT stage of resected PDAC patients according to the novel UICC staging protocol (8th edition) significantly improves patient stratification, whereas introduction of an extended N stage protocol does not demonstrate high clinical relevance in our cohorts.     

Screening of Differentially Expressed Genes among Various TNM Stages of Lung Adenocarcinoma by Genomewide Gene Expression Profile Analysis

Background: To further investigate the molecular basis of lung cancer development, we utilize a microarrayto identify differentially expressed genes associated with various TNM stages of adenocarcinoma, a subtype withincreasing incidence in recent years in China. Methods: A 35K oligo gene array, covering about 25,100 genes,was used to screen differentially expressed genes among 90 tumor samples of lung adenocarcinoma in variousTNM stages. To verify the gene array data, three genes (Zimp7, GINS2 and NAG-1) were confirmed by real-timeRT-PCR in a different set of samples from the gene array. Results: First, we obtained 640 differentially expressedgenes in lung adenocarcinomas compared to the surrounding normal lung tissues. Then, from the 640 candidateswe identified 10 differentially expressed genes among different TNM stages (Stage I, II and IIIA), of which Zimp7,GINS2 and NAG-1 genes were first reported to be present at a high level in lung adenocarcinoma. The resultsof qRT-PCR for the three genes were consistent with those from the gene array. Conclusions: We identified 10candidate genes associated with different TNM stages in lung adenocarcinoma in the Chinese population, whichshould provide new insights into the molecular basis underlying the development of lung adenocarcinoma andmay offer new targets for the diagnosis, therapy and prognosis prediction.     

Prognostic Role of Nucleophosmin in Colorectal Carcinomas

Aim: Recent research suggests that nucleophosmin (NPM) may be a prognostic marker in colorectalcarcinomas (CRC). We here tested its use to predict the survival of CRC patients. Methods: We investigatedNPM expression by immunohistochemistry in histologically normal to malignant colorectal tissues and evaluatedits association with clinicopathological variables. Overall and disease-free survival after tumor removal werecalculated by the Kaplan-Meier method, and differences in survival curves were analyzed by the log-rank test.The Cox proportional hazards model was used for multivariate analysis of prognostic factors. Results: NPMexpression was found significantly upregulated in CRC compared to adjacent colorectal tissue, villous adenoma,tubular adenoma and normal colorectal mucosa (p<0.05 for all). NPM expression was statistically linked tocancer embolus, lymph node metastasis, differentiation grade, and recurrence of CRC. Overall and disease-freesurvival of NPM-negative CRC patients tended to be better than those for patients with NPM-positive lesions(log-rank statistic, p<0.05 for all). Multivariate analysis indicated NPM expression as an independent prognosticindicator for CRC patients (p<0.05 ). Conclusion: Our results suggest that NPM expression can predict thesurvival of CRC patients. Prognosis of CRC is determined by not only many known prognostic factors but alsoby NPM expression.     

Predictors for Survival and Distribution of 21-Gene Recurrence Score in Patients With Pure Mucinous Breast Cancer: A SEER Population-Based Retrospective Analysis

Background

Pure mucinous breast cancer (PMBC) is a rare pathologic type of breast cancer, the prognostic factors of which have not been clearly defined. This study aimed to analyze the prognostic markers and distribution of 21-gene recurrence score (RS) in patients with PMBC.

Prognostic Evaluation of Tumor-Stroma Ratio in Patients with Early Stage Cervical Adenocarcinoma Treated by Surgery

Background: The tumor-stroma ratio (TSR) represents the percentage of neoplastic cell components comparedto the combined area of neoplastic cells and the surrounding tumor-induced stroma. A low TSR (predominationof stromal component) has been demonstrated to be an independent adverse prognostic factor in cancers ofseveral organs. In cervical carcinoma patients, TSR has been evaluated in only one previous study with differenthistological types. The present study aimed to assess the prognostic value of TSR in early stage cervical cancerpatients with adenocarcinoma histology only. Materials and Methods: Histological slides of patients with earlystage (IB-IIA) cervical adenocarcinoma who underwent surgical treatment between January 2003 and December2011 were reviewed. Patients who had received preoperative chemotherapy were excluded. TSR was categorizedas low (<50%) and high (≥50%). Correlations between TSR and clinicopathological variables were evaluated.Prognostic values of TSR and other variables were estimated using Cox’s regression. Results: Of 131 patients;38 (29.0%) had low TSR and 93 (71.0%) had high TSR. The patients with low TSR had significantly higherproportions of deep cervical stromal invasion (outer third of wall, p=0.011; residual stroma less than 3 mm,p=0.008) and parametrial involvement (p=0.026). Compared to the patients with high TSR, those with low TSRtended to have lower 5-year disease-free survival rate (83.8% versus 88.9%) and overall survival rate (85.6%versus 90.3%), although the differences were not statistically significant. Low TSR was significantly associatedwith decreased overall survival in univariate analysis (HR 2.7; 95% CI 1.0-7.0; p=0.041), but not in multivariateanalysis. TSR was not significantly associated with decreased disease-free survival. Conclusions: Low TSR isassociated with decreased overall survival in patients with early stage cervical adenocarcinoma treated bysurgery. However, it was not found to be an independent prognostic predictor in this study.     

Synchronous Advanced Colorectal Neoplasia: Clinicopathologic Features and Prognostic Significance

Objective: This study aimed to compare the clinico-pathologic features, recurrence rate and disease-free survival between colorectal cancers (CRCs) with synchronous advanced colorectal neoplasia (SCN) and solitary CRCs to determine the prognostic significance of SCN. Methods: A retrospective review of prospectively collected data of patients with CRCs was conducted in Phramongkutklao Hospital from January 2009 to December 2014. Patients were categorized in 3 groups: 1) solitary CRCs, 2) CRCs with advanced colorectal adenomas (ACAs) but having no another cancer and 3) synchronous colorectal cancers (S-CRCs) with or without ACAs. Patients undergoing curative resection and complete standard adjuvant treatment were recruited to evaluate the prognostic significance of SCN.  Clinicopathologic features, recurrence rate and disease-free survival were analyzed to compare among different groups.  Result: Among 328 recruited patients, 282 were classified as solitary CRCs (86%), 23 as CRCs with ACAs (7%) and 23 as S-CRCs (7%). Patients with CRCs with SCN (groups 2 and 3) were significantly older than patients with solitary CRCs (p <0.01), and SCN was found more commonly among males (15.2%) than females (12.3%) (p=0.045). In all, 288 patients achieved a curative resection and accomplished complete standard postoperative adjuvant treatment. Of these, the accumulative number of patients experiencing tumor recurrence was 11.8, 21.2, 24.6, 26.4 and 26.7% at the 1-, 3-, 5-, 7- and 10-year surveillance period, respectively. The disease-free survival of the groups with SCN was marginally higher than that of solitary CRCs groups (p=0.72) (solitary CRCs, 120.7±4.4 months; CRCs/ACAs, 127.4±13.9 months and S-CRCs: 126.2±13.6 months). Conclusion: CRCs with SCN were found at a more advanced age than those with solitary CRCs. SCN was found more often among males than females. After achieving curative resection and complete adjuvant treatment, the recurrence rate and disease-free survival of CRCs with SCN did not significantly differ from those of solitary CRCs.     

结直肠癌美国癌症联合会TNM分期第5、6版与第7版的差异及预后分析和比较

目的 比较结直肠癌AJCC分期第5、6版和第7版对患者生存时间预后评估的差异,评价新的结直肠癌美国癌症联合会TNM分期标准的临床应用价值。方法 回顾性分析1995-2007年在天津市人民医院接受治疗并具有完整临床病理资料的3 671例患者,以三版分期标准比较其预后情况。结果 结直肠癌第7版AJCC分期在T、N、M分期方面均进行了调整,与第5、6版相比,分期标准更为精细化,可以更好地对不同临床结果的患者进行区分。结论 与第5、6版相比,第7版分期标准更为合理,精确,但其具体临床价值仍有待进一步探索。