Clinical implications of acellular mucin pools in resected rectal cancer with pathological complete response to neoadjuvant chemoradiation1

Aim Approximately 20% of rectal cancers treated with neoadjuvant chemoradiation achieve a pathological complete response (pCR), which is associated with an improved oncological outcome. However, in a proportion of patients with a pCR, acellular pools of mucin are present in the surgical specimen. The aim of this study was to evaluate the clinical implications of acellular mucin pools in patients with rectal adenocarcinoma achieving a pCR after neoadjuvant chemoradiation followed by proctectomy. Method A single‐centre colorectal cancer database was searched for patients with clinical Stage II and Stage III rectal adenocarcinoma who achieved a pCR (i.e. ypT0N0M0) after neoadjuvant chemoradiation followed by proctectomy between 1997 and 2007. Patients were categorized according to the presence or absence of acellular mucin pools in the resected specimen, and groups were compared. Patient demographics, tumour and treatment characteristics, and oncological outcomes were recorded. Primary outcomes were 3‐year local and distant recurrences, and disease‐free and overall survivals. Results Two hundred and fifty‐eight patients with clinical Stage II or Stage III rectal adenocarcinoma were treated by neoadjuvant chemoradiation. Fifty‐eight of these patients had a 58 pCR. Eleven of the 58 patients with a pCR had acellular mucin pools in the surgical specimen. The median follow up was 40 months. The groups were statistically similar with respect to demographics, chemoradiation regimens, distance of tumour from the anal verge, clinical stage and surgical procedure. No patient had local recurrence. Patients with acellular mucin pools had increased distant recurrence (21%vs 5%), decreased disease‐free survival (79%vs 95%) and decreased overall survival (83%vs 95%) rates, although none of these differences was statistically significant. Conclusion The presence of acellular mucin pools in a proctectomy specimen with a pCR does not affect local recurrence, but may suggest a more aggressive tumour biology.     

System‐based factors influencing intraoperative decision‐making in rectal cancer by surgeons: an international assessment

Aim Sound surgical judgement is the goal of training and experience; however, system‐based factors may also colour selection of options by a surgeon. We analysed potential organizational characteristics that might influence rectal cancer decision‐making by an experienced surgeon. Method One hundred and seventy‐three international centres treating rectal cancer were invited to participate in a survey assessment of key treatment options for patients undergoing curative rectal‐cancer surgery. The key organizational characteristics were analysed using multivariate methods for association with intra‐operative surgical decision‐making. Results The response rate was 71% (123 centres). Sphincter‐saving surgery was more likely to be performed at university hospitals (OR = 3.63, P = 0.01) and by high‐caseload surgeons (OR = 2.77 P = 0.05). A diverting stoma was performed more frequently in departments with clinical audits (OR = 3.06, P = 0.02), and a diverting stoma with coloanal anastomosis was more likely in European centres (OR = 4.14, P = 0.004). One‐stage surgery was less likely where there was assessment by a multidisciplinary team (OR = 0.24, P = 0.02). Multivariate analysis showed that university hospital, clinical audit, European centre, multidisciplinary team and high caseload significantly impacted on surgical decision‐making. Conclusion Treatment variance of rectal cancer surgeons appears to be significantly influenced by organizational characteristics and complex team‐based decision‐making. System‐based factors may need to be considered as a source of outcome variation that may impact on quality metrics.     

The use of molecular markers as a method to predict the response to neoadjuvant therapy for advanced stage rectal adenocarcinoma

Aim The response to combined neoadjuvant therapy for advanced stage rectal adenocarcinoma is predictive of outcome. In addition to both clinical and pathological features, the expression of a variety of molecules may provide another method of identifying tumour responsiveness to pre‐operative therapy. The aim of this study was to evaluate several markers in the apoptotic pathway as well as expression of Cox‐2 and vascular endothelial growth factor (VEGF) to determine their ability to predict response to neoadjuvant therapy. Method In total, 152 patients with advanced rectal adenocarcinoma were treated with neoadjuvant therapy followed by resection. Paraffin‐embedded sections obtained before and after therapy were assessed by immunohistochemical staining for Cox‐2, VEGF, p53, p21, p27, Bax, BCL‐2 and apoptosis protease‐activating factor 1 (APAF‐1). These stains were correlated with tumour regression grade, complete pathological response and T‐downstaging of the surgical specimen. Clinical and pathological data were also collected. Data were analysed using the χ² and Spearman’s correlation tests. Results Pathological complete response was seen in 24.5% of patients. Amongst the apoptosis‐associated markers, only APAF‐1 expression was found to be significantly associated with tumour regression grade (P < 0.001), complete pathological response (P < 0.031) and T‐downstaging (P < 0.004). On multivariate analysis, APAF‐1 expression was found to be independently associated with good tumour regression grade. In contrast, overexpression of Cox‐2 and VEGF in pretreatment biopsies was related to less tumour regression (P < 0.003) and less likelihood of T‐downstaging (P < 0.03). Conclusion Immunohistochemical evaluation of initial biopsy specimens of rectal cancer with APAF‐1, Cox‐2 and VEGF may predict tumour response to neoadjuvant therapy in patients with advanced rectal adenocarcinoma. Those with an expected limited response may be considered for other investigational neoadjuvant protocols.     

Pharmacokinetic analysis based on dynamic contrast-enhanced MRI for evaluating tumor response to preoperative therapy for oral cancer

Purpose:

To evaluate whether a pharmacokinetic analysis is useful for monitoring the response of oral cancer to chemoradiotherapy (CRT).

Materials and Methods:

Twenty‐nine patients were included. They underwent dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) before and after CRT. The DCE‐MRI data were analyzed using a Tofts and Kermode (TK) model. The histological evaluation of the effects of CRT was performed according to Ohboshi and Shimosato's classification.

Results:

None of the pre‐CRT parameters were significantly different between the responders and nonresponders. The post‐CRT volume of the extravascular extracellular space (EES) per unit volume of tissue (v_e) of responders (0.397 ± 0.080) was higher than that of nonresponders (0.281 ± 0.076) (P = 0.01). The change of the v_e between the pre‐ and post‐CRT of the responders (0.154 ± 0.093) was larger than that of the nonresponders (0.033 ± 0.073) (P = 0.001). Therefore, the increase in the v_e strongly suggested a good tumor response to CRT, which reflected an increase of the EES secondary to the destruction of the cancer nest. The changes in the volume transfer constant (K^trans) were significantly different between the responders and nonresponders (P = 0.018).

Conclusion:

Both the increase of the v_e and the elevation of permeability (K^trans) were indicative of a good tumor response to CRT. The pharmacokinetic analysis had potential for monitoring the histopathological response to CRT. J. Magn. Reson. Imaging 2012;36:589–597. © 2012 Wiley Periodicals, Inc.     

Gastric-type mucinous adenocarcinoma of the uterine cervix with neoadjuvant therapy mimicking clear cell carcinoma

Gastric-type mucinous adenocarcinoma, an uncommon subtype of cervical carcinoma, is characterized by a distinct morphology and immunophenotype. Herein, we report a case of a 71-year-old woman who received neoadjuvant radiotherapy and chemotherapy after cervical biopsy revealed moderately differentiated invasive endocervical adenocarcinoma. Subsequently, the outside patient underwent radical hysterectomy with bilateral salpingo-oophorectomy. The post-neoadjuvant therapy hysterectomy specimen showed tumor cells with clear cytoplasm, hyperchromatic nuclei with irregular contours, which mimicked clear cell carcinoma. However, immunohistochemical staining showed that these tumor cells were positive for carcinoembryonic antigen, cytokeratin 7 (diffuse), and cytokeratin 20 (patchy), After review of the pretreatment cervical biopsy specimen, the tumor was favored to represent a gastric-type mucinous adenocarcinoma of the cervix. Pathologists should be aware of this rare tumor and its post-neoadjuvant therapy morphologic changes, which can make diagnosis more challenging.     

Surgery for cholangiocarcinoma: the role of liver transplantation

Liver transplantation alone for unresectable hilar cholangiocarcinoma (CCA) is fraught with frequent recurrence and poor long-term survival. The Mayo Clinic developed a novel therapeutic protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) in 1993 to treat patients with unresectable hilar CCA or CCA arising in the setting of PSC. Aim. We recently reviewed our experience over the past 14 years with the specific aim to evaluate the long-term outcomes of CCA patients treated according to our study protocol. Methods. We analyzed data from all patients enrolled in the Mayo Clinic liver transplant protocol since 1993. Statistical data analysis of recurrence and survival rates was performed using the Kaplan-Meier method. Results. 148 patients were enrolled in the protocol. Of 90 patients who completed neoadjuvant therapy and subsequent OLT, 71 are alive and 19 have died – only 8 due to recurrent CCA. Nineteen patients are awaiting OLT and 39 were removed from the protocol owing to disease progression or death. Overall, 1-, 3-, and 5-year patient survival was 82%, 63%, and 55%, respectively; 1-, 3-, and 5-year survival after OLT was 90%, 80%, and 71%. Conclusions. Neoadjuvant chemoradiation and OLT achieves significantly lower recurrence and higher long-term survival rates than resection, OLT alone, or medical treatment in hilar CCA. Additional experience at independent transplant centers is necessary to confirm these encouraging results, address the role of neoadjuvant therapy and liver transplantation versus conventional resection, determine appropriate inclusion/exclusion criteria, and define the risk of disease progression while awaiting transplantation.     

替吉奥联合奥沙利铂治疗进展期胃癌的疗效及对癌组织中MMP-9和VEGF表达的影响

目的观察替吉奥联合奥沙利铂治疗进展期胃癌的疗效,并探讨其对癌组织中基质金属蛋白酶-9(MMP-9)和血管内皮生长因子(VEGF)表达的影响。方法 85例进展期胃癌患者分为观察组(n=45)和对照组(n=40),均接受新辅助化疗方案:观察组给予替吉奥胶囊联合奥沙利铂;对照组给予5-氟尿嘧啶+亚叶酸钙联合奥沙利铂。观察2组近期疗效、不良反应及化疗前后癌组织中MMP-9和VEGF表达的变化。结果 2组客观缓解率无显著差异(P0.05),观察组临床受益率显著高于对照组(P0.05);观察组重度骨髓抑制和胃肠道发生率低于对照组(P0.05);2组化疗后MMP-9及VEGF表达阳性区灰度值均较治疗前均显著下降(P0.01),组间比较差异显著(P0.01)。结论替吉奥胶囊联合奥沙利铂可提高进展期胃癌患者的临床受益率,且能有低癌组织中MMP-9和VEGF的表达。     

Caspase-3及p53预测口腔鳞癌动脉灌注新辅助化疗敏感性的研究

目的：探讨口腔鳞癌在行区域性动脉灌注DF方案新辅助化疗时,Caspase-3及p53预测化疗敏感性的价值。方法：选取76例经区域性动脉灌注DF方案行新辅助化疗及手术的口腔癌患者,检测其癌组织中Caspase-3及p53的表达及化疗后的病理学变化,分析Caspase-3及p53不同表达者与化疗疗效间的关系。结果：1)Caspase-3表达阳性者有效率显著高于表达阴性者(P<0.05),而p53表达阳性者有效率显著低于表达阴性者(P<0.05);2)Caspase-3表达阳性同时p53表达阴性者化疗有效率为92.59%,显著高于其他表达类型(P<0.05);而Caspase-3表达阴性同时p53表达阳性者,化疗有效率为27.78%,显著低于其他表达类型(P<0.05)。结论：在预测口腔鳞癌行动脉灌注DF方案行新辅助化疗时,Caspase-3和p53均可作为敏感性的分子标记物,而且两项指标的表达水平联合预测显著高于单项指标预测。     

Aspirin as a neoadjuvant agent during preoperative chemoradiation for rectal cancer

Background:

Recently, many studies have suggested a possible adjuvant role of aspirin in colorectal cancer, reporting a positive prognostic effect with its use in patients with established disease. The aim of this study was to investigate the anticancer effect of aspirin use during preoperative chemoradiation for rectal cancer.

Methods:

Two hundred and forty-one patients with stage II–III rectal cancer and candidates for chemoradiation (CRT) were selected and assigned to two groups: group 1, patients taking aspirin at the time of diagnosis, and group 2, all others. Treatment and oncological outcomes were explored.

Results:

Aspirin use was associated with a higher rate of tumour downstaging (67.6% vs 43.6%, P=0.01), good pathological response (46% vs 19% P<0.001), and a slightly, although not significant, higher rate of complete pathological response (22% vs 13% P=0.196). Aspirin use was also associated with a better 5-year progression-free survival (86.6% vs 67.1% hazard rate (HR)=0.20; 95% CI=0.07–0.60) and overall survival (90.6% vs 73.2% HR=0.21; 95% CI=0.05–0.89). Although chance of local relapse was similar (HR=0.6; 95% CI=0.06–4.5), aspirin use was associated with a lower risk of developing metastasis (HR=0.30; 95% CI=0.10–0.86).

Conclusions:

Aspirin might have anticancer activity against rectal cancer during preoperative CRT. This finding could be clinically relevant and should be further investigated with randomised trials.     

卵巢癌治疗新进展

卵巢癌是继子宫内膜癌及宫颈癌发生率居第三的妇科恶性肿瘤,而其死亡率却居妇科恶性肿瘤之首。卵巢癌的治疗一直是临床工作面临的最艰巨的挑战。传统的根治性手术联合辅助性化疗仍是其基本的治疗方法,新辅助化疗、放疗、生物治疗、免疫治疗和分子靶向治疗给中晚期的卵巢癌治疗提供了新的选择。本文综述卵巢癌的治疗现状及最新的研究进展。