Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer

IntroductionWe experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil.Presentation of caseAfter administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence.DiscussionIn these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover.ConclusionAlthough cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure.     

C反应蛋白对乳腺癌新辅助化疗患者疗效评估的影响

【摘要】〓目的〓本研究旨在运用C反应蛋白(CRP)作为全身及肿瘤局部炎症反应的参数,分析其与新辅助化疗前后乳腺癌患者的临床病理生物学因素之间的关系及其对新辅助化疗疗效的影响。方法〓本研究回顾性分析了我院乳腺外科2001年1月至2010年6月确诊并接受新辅助化疗的Ⅱ-Ⅲ期乳腺癌患者共215例。按不同的病理完全缓解(pCR)标准分组(包括原发灶和淋巴结及仅包括原发灶),统计学分析CRP与新辅助化疗患者的临床病理特征及病理完全缓解(pCR)之间的关系。结果〓达到pCR的患者较非pCR患者的CRP均值更低(P=0.035和P=0.032),CRP对pCR(仅包括原发灶)有良好的预测价值(P<0.001)。结论〓新辅助化疗前CRP水平有助于预测新辅助化疗疗效。     

Bcl-2 predicts response to neoadjuvant chemotherapy and is overexpressed in lymph node metastases of urothelial cancer of the bladder

PurposeTo assess whether Bcl-2, an inhibitor of the apoptotic cascade, can predict response to neoadjuvant chemotherapy in patients with urothelial cancer of the bladder (UCB).MethodsBcl-2 expression was analyzed in 2 different tissue microarrays (TMAs). One TMA was constructed of primary tumors and their corresponding lymph node (LN) metastases from 152 patients with chemotherapy-naive UCB treated by cystectomy and pelvic lymphadenectomy (chemotherapy-naive TMA cohort). The other TMA was constructed of tumor samples obtained from 55 patients with UCB before neoadjuvant chemotherapy (transurethral resection of the bladder cancer) and after cystectomy with pelvic lymphadenectomy (residual primary tumor [ypT+], n = 38); residual LN metastases [ypN+], n = 24) (prechemotherapy/postchemotherapy TMA cohort). Bcl-2 overexpression was defined as 10% or more cancer cells showing cytoplasmic immunoreactivity.ResultsIn both TMA cohorts, Bcl-2 overexpression was significantly (P<0.05) more frequent in LN metastases than in primary tumors (chemotherapy-naive TMA group: 18/148 [12%] in primary tumors vs. 39/143 [27%] in metastases; postchemotherapy TMA: ypT+7/35 [20%] vs. ypN+11/19 [58%]). In the neoadjuvant setting, patients with Bcl-2 overexpression in transurethral resection of the bladder cancer specimens showed significantly (P = 0.04) higher ypT stages and less regression in their cystectomy specimens than did the control group, and only one-eighth (13%) had complete tumor regression (ypT0 ypN0). In survival analyses, only histopathological parameters added significant prognostic information.ConclusionsBcl-2 overexpression in chemotherapy-naive primary bladder cancer is related to poor chemotherapy response and might help to select likely nonresponders.     

食管癌新辅助放化疗疗效预测分子标志物

局部晚期食管癌单纯手术治疗预后较差,新辅助放化疗并手术治疗的方案可明显延长食管癌患者的总体生存时间.目前,该治疗方案已成为欧美国家及我国对局部晚期食管癌进行规范化治疗的指南.然而,由于只有经新辅助放化疗后获得病理缓解的患者可从中获益,治疗无反应的患者预后可能比单纯手术更差.因此,预测食管癌新辅助放化疗的疗效,区分优势人群和耐受人群,从而实现个体化的治疗极为重要.分子标记物用于预测食管癌新辅助放化疗的疗效研究前景广阔,有望广泛应用于临床实践,指导局部晚期食管癌个体化治疗方案的决策.     

Ultrasound-based prediction of pathologic response to neoadjuvant chemotherapy in breast cancer patients

BackgroundAccuracy in predicting pathologic response to neoadjuvant chemotherapy (NACT) in breast cancer is essential for the determination of therapeutic efficacy and surgical planning. This study aimed to assess the precision of ultrasound (US) for predicting pathologic complete response (pCR = ypT0) after NACT.MethodsThis retrospective mono-center study included 124 invasive breast cancer patients treated with NACT. Patients received US before and after NACT with documentation of clinical partial response (cPR) and clinical complete response (cCR). Post-operatively, the pathologic response was defined as absence of tumor cells (ypT0), presence of non-invasive tumor cells (ypTis) or invasive tumor cells (ypTinv). Sensitivity and specificity of US as well as false negative rate (FNR), negative predictive value (NPV) and positive predictive value (PPV) were analysed for receptor subtypes. A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR.Results50 patients (40.3%) achieved pCR, 39 (78.0%) had a corresponding cCR. Overall sensitivity was 60.8% and specificity 78.0% for US-predicted remission. NPV and FNR differed substantially between subtypes. NPV was highest (75.0%) in triple negative (TN) subtype, while FNR was low (37.5%). Therefore, pathological response was most accurately predicted for TN cancers. NPV for human-epidermal-growth-factor-receptor-2-positive/hormone-receptor-positive (HER2+/HR+) was 55.6%, for HER2+/HR- 64.3% and for HER2-/HR+ 16.7%, FNRs were 40.0%, 71.4% and 32.3%, respectively. Receptor subtypes impacted pCR significantly (p-value: 0.0033), cCR correlated positively with pCR (p-value: 0.0026).ConclusionUS imaging is insufficient to predict pCR with adequate accuracy. Receptor subtypes, however, affect diagnostic precision of US and pathologic outcome.     

An experimental study of regional chemotherapy using CDDP-loaded microspheres for esophageal cancer

Purpose. The purpose of this study was to assess the antitumor effects of cisplatin-loaded microspheres (CDDP-MS) and the efficacy of the administration of CDDP-MS into the mediastinum. Methods. To evaluate the antitumor effect, we first performed a paratumoral injection of CDDP-MS to FF6 tumor-bearing DA rats to compare its effect with that of the intraperitoneal injection of a CDDP solution at different doses. Results. In the CDDP-MS groups the tumor growth was effectively delayed in proportion to the dosage of CDDP-MS. All rats treated with the CDDP solution at a dose of 10 mg/kg died within 1 week, while no rats treated with CDDP-MS even at a CDDP dose of 20 mg/kg were lost. In the second experiment, which was designed to determine the delivery of the microspheres-released CDDP to various organs, CDDP-MS was injected directly into the mediastinum via the diaphragm in male Wistar rats. In the CDDP-MS group, the plasma CDDP concentration stayed significantly lower than that in the CDDP solution (intravenous) group while the tissue CDDP concentration in the paratracheal lymph nodes was higher. Moreover, the lymph node-to-kidney platinum ratio was eight times higher in the rats given CDDP-MS intramediastinally than in those given the CDDP solution intravenously. Conclusion. These results demonstrate that a high dose of CDDP can be administered with less systemic side effects by means of encapsulation in the microspheres, and that the administration of CDDP-MS into the mediastinum is more effective for delivering CDDP to the paratracheal lymph nodes. As a regional chemotherapy after esophageal cancer operation, the injection of CDDP-MS into the mediastinum for targeting of the lymph nodes thus promises to be an effective treatment. Received: February 16, 2001 / Accepted: September 11, 2001     

Salvage esophagectomy after definitive chemotherapy and radiotherapy for advanced esophageal cancer

BACKGROUND: Although local recurrence of advanced esophageal cancer is frequent after definitive chemoradiotherapy (CRT), the clinical benefit of salvage esophagectomy has not been elucidated. METHODS: We reviewed 27 patients with squamous-cell cancer who underwent esophagectomy after definitive CRT (> or = 50 Gy) (salvage group) and 28 patients who underwent planned esophagectomy after neoadjuvant CRT (30 to 45 Gy) (neoadjuvant group). RESULTS: The preoperative albumin level and vital capacity were significantly lower in the salvage group than in the neoadjuvant group. Two patients (7.4%) from the salvage group who underwent extended esophagectomy with three-field lymphadenectomy died of postoperative complications, but no deaths occurred after less-invasive surgery. There was no difference of overall postoperative survival between the salvage and neoadjuvant groups. CONCLUSIONS: The outcome of salvage esophagectomy after definitive CRT was similar to that of planned esophagectomy after neoadjuvant CRT. Less-invasive procedures might be better for salvage esophagectomy because of the high operative risk.     

Accuracy of pathologic examination in detection of complete response after chemoradiation for esophageal cancer

BACKGROUND: Although a substantial proportion of patients undergoing neoadjuvant chemoradiation for invasive esophageal cancer develop a pathologic complete response (pCR), these patients nonetheless have a poor 5-year survival rate. We hypothesized that routine pathologic examination fails to identify some residual cancer. METHODS: Patients undergoing esophagectomy for cancer at 2 tertiary care centers were identified. Archived tumor blocks were retrieved for patients with pCR, sectioned at 50-mum intervals and reexamined for residual cancer. RESULTS: Seventy patients underwent neoadjuvant chemoradiation. Tumor blocks were available for 23 of 26 complete responders. A total of 159 blocks were reexamined. One patient was found to have a possible focus of residual invasive adenocarcinoma versus high-grade dysplasia. The remaining 22 patients had no residual disease. CONCLUSIONS: A more aggressive examination protocol for postchemoradiation esophagectomy specimens may not result in significant upstaging. Inadequate pathologic examination is likely not a major factor in the suboptimal survival in patients with pCR.     

fMRI(磁共振功能成像)对乳腺癌新辅助化疗评估的研究进展

【摘要】〓能够早期评估乳腺癌新辅助化疗疗效的方法很大程度上有助于病人治疗方案的制定,所以对于找寻精准且无创的方法的需求则日益上升。目前,MRI技术能够根据肿瘤大小、形态及强化程度等形态学变化对疗效进行评估,而且已有越来越多新兴技术能够从微观分子层面早期反映新辅助化疗后肿瘤变化,这些技术包括动态对比增强(DCE-MRI)、磁共振波谱(MRS)、磁共振弥散加权成像(DWI)、体素内不相干运动(IVIM)。作者综述MRI新技术在评估乳腺癌新辅助化疗疗效中的应用。     

Cathepsin-D和nm23在乳腺癌蒽环类新辅助化疗中疗效的预测价值

目的探讨乳腺癌病人肿瘤组织中分子生物学标记物的表达与含蒽环类新辅助化疗有效率的关系。方法检测复旦大学附属肿瘤医院2000年1月至2006年8月173例乳腺癌新辅助化疗病人化疗术前或术后标本中ER、PR、Her-2/neu等15种分子标记物的表达情况,分析这些分子标记物的表达在新辅助化疗中的疗效预测价值。结果nm23或Cathepsin-D阴性病人化疗疗效显著优于阳性病人,多因素回归分析提示Cathepsin-D是独立的新辅助化疗疗效预测指标。结论Cathepsin-D可能作为乳腺癌新辅助化疗(蒽环类)敏感性的独立预测指标。     

Increased risk of thromboembolism in esophageal cancer patients treated with neoadjuvant chemoradiotherapy

Background

Neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) patients may increase the formation of thromboembolic events (TEEs). We analyzed the incidence and impact of TEEs in EC patients treated with platinum-based CRT.

Methods

A total of 336 patients with EC underwent an esophagectomy, of which 110 patients received neoadjuvant CRT (41.4 Gy with concurrent Carboplatin/Paclitaxel). Patients were matched based on pre- and perioperative characteristics.

Results

Preoperatively, 9 (8.2%) patients with neoadjuvant CRT (P = .004) were diagnosed with TEEs. Despite delay until surgery (P = .021), the postoperative course did not differ. In multivariate analysis, a history of deep vein thrombosis (P = .005) and neoadjuvant CRT (P = .004) were identified as risk factors. Postoperatively, there were no differences in TEEs (P = .560) observed. In multivariate analysis, a history of pulmonary embolism (P = .012) was identified as a risk factor for postoperative TEEs.

Conclusions

Preoperatively, EC patients treated with neoadjuvant CRT have an increased risk to develop a TEE, especially those with a previous history of TEE. After surgery no increased incidence was observed. We recommend secondary prophylaxis during neoadjuvant treatment in this high-risk group.     

The efficacy of neoadjuvant chemotherapy in invasive bladder cancer

Radical cystectomy is the gold standard in the treatment of invasivebladder cancer. However, five-year disease-free survival is low mostprobably due to micrometastatic disease at the time of surgery. Theneoadjuvant chemotherapy may be performed as the first line managementfor invasive bladder tumors in order to treat micrometastases found at thediagnosis and improve resectability of larger neoplasms. A total of 43patients diagnosed with invasive bladder tumors and 11 patients receivedneoadjuvant chemotherapy. The mean age of patients was 64 (43–74) years,and mean follow-up period was 52 months (12–114). Neoadjuvantchemotherapy protocol consisted of methotrexate, vinblastine, doxorubicin,and cisplatin (MVAC) or cisplatin, methotrexate, and cisplatin (CMV). Allpatients in neoadjuvant chemotherapy group underwent radicalcystectomy. There was no significant difference between the groups withrespect to disease-free survival time and overall survival time. In patientswho received neoadjuvant chemotherapy, the respective disease-free andoverall survival times were 31 months and 36 months versus 30 months and35 months in patients who were treated with surgery only (p > 0.05). Five-year survival rates were 36% and 31% in the chemotherapy and no-chemotherapy groups, respectively. In the present study, 5-year survivalrate was not affected by neoadjuvant chemotherapy in invasive bladdertumor. Complete pathological remission (stage p0) was found in 28% andpathological downstaging (stage < T2) was seen in 9% of patients in theneoadjuvant chemotherapy group. Five-year survival rates were 75% and14.2% in patients who responded to chemotherapy, and in patients with noresponse, respectively (p < 0.05). The most favorable prognostic factor inthis study was the response to neoadjuvant chemotherapy revealed ascomplete remission or pathological downstaging. The most important issueremains the prediction of patients who would respond and benefit fromneoadjuvant chemotherapy.     

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目的　探讨乳腺癌新辅助化疗中Ki- 6 7、bcl- 2和AI表达率与临床疗效的关系。方法　2 0 0 2年1月至2 0 0 3年6月对5 8例可手术女性乳腺癌病人采用CEF方案新辅助化疗3个周期。对资料完整的4 2例,检测化疗前后Ki -6 7、bcl- 2及肿瘤细胞凋亡指数(AI)的变化。结果　化疗有效率为6 2. 1%。Ki 6 7高表达乳腺癌有效率高(P <0 .0 5 )。疗效与bcl- 2表达及AI值无明显关系。结论　可手术乳腺癌采用CEF方案新辅助化疗,Ki- 6 7表达情况对预测化疗效果具有重要价值。     

Usefulness of positron emission tomography for assessing the response of neoadjuvant chemoradiotherapy in patients with esophageal cancer

BACKGROUND: In this study, we retrospectively assessed the performance of 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) compared with computed tomography (CT) and esophagography for assessing the response of advanced esophageal squamous cell carcinoma (SCC) to neoadjuvant chemoradiotherapy. METHODS: We studied 10 patients with thoracic esophageal SCC who received neoadjuvant chemoradiotherapy followed by surgery. Tumor response was assessed by CT, endoscopy, esophagography and FDG-PET before and after neoadjuvant treatment. RESULTS: Assessment of the rate of decrease in standardized uptake value (SUV) revealed a partial response (more than 50% decrease) in 5 (50%) of the patients, and assessment of length decrease of FDG uptake showed a partial response in 9 (90%) of the patients. Comparison of the histological response and the rate of decrease of various parameters revealed significant associations between histological response and tumor length (P <0.05), SUV after neoadjuvant therapy (P <0.05), and reduction in the extent of FDG uptake (P <0.01). However histological response was not significantly correlated with the rate of reduction of SUV, for both CT and esophagography. CONCLUSIONS: FDG-PET may be of considerable value for predicting the pathologic response of esophageal SCC to neoadjuvant therapy. Despite assessment of SUV before neoadjuvant therapy, low FDG uptake after therapy and reduction in the extent of FDG uptake may provide a reliable assessment of the response to therapy.     

局部晚期乳癌新辅助化疗(附5例临床报告)

对5例局部晚期不能根治切除的乳癌(T_4N_2M_0/T_4N_2M_1),根据体外药物敏感试验结果,进行化疗,5例病人化疗均有效(CR 1例,PR 4例),原发病灶由T_4降为T_2,转移灶缩小或消失,使不能手术的乳癌变成可以手术切除,从而提高治疗效果。在肿瘤个体化治疗方面作了有益的尝试。     

食管癌辅助化疗期间并发症对预后的影响

目的探讨食管癌患者术后辅助化疗器件发生并发症对预后的影响。 方法回顾分析2003—2011年南京鼓楼医院接受食管癌手术治疗并采用辅助化疗的738例患者的临床资料,并随访至2017年12月。采用多变量Cox比例风险模型分析辅助化疗期间发生血液系统和非血液系统并发症与短期和长期病死率之间的联系。 结果在738例患者中,73例(9.9% )患者因辅助化疗产生并发症需要急诊住院治疗,血液系统并发症可导致术后90 d病死率升高(HR＝5.63,95% CI：1.26～24.81),在肿瘤分期为0～Ⅱ期的腺癌、无论切缘是否有残留的患者中尤为明显,食管腺癌术后5年疾病相关病死率显著升高(HR＝3.21,95% CI：1.05～10.33)。在预计预后较差组(肿瘤分期Ⅲ～Ⅳ期)发生非血液系统并发症术后5年病死率较高(HR＝2.34,95% CI：1.17～4.89)。其他亚组患者发生血液系统或非血液系统并发症并不影响5年病死率。 结论食管癌患者接受食管切除术后行辅助化疗,发生相关并发症可能对患者近期及远期病死率产生不利影响。     

Impact of neoadjuvant therapy of perioperative morbidity in patients with esophageal cancer

BACKGROUND: Conflicting results of preoperative radiochemotherapy in patients with esophageal cancer have been obtained; only patients with a complete pathological response seem to benefit from this therapy. However, there is evidence that preoperative radiochemotherapy leads to considerable postoperative morbidity. Therefore, postoperative morbidity was retrospectively investigated in 82 patients with an esophageal cancer who received preoperative radiochemotherapy. METHODS: One hundred twenty-two consecutively operated on patients were included (1991 to 2001). Preoperative radiochemotherapy was initiated in 1994 for cT >1, cNx, cM0 regardless of histology (n = 82); 36 Gy was applied (1.8 Gy daily, days 1 to 5, weeks 1 to 4), concurrently 5-fluorouracil (500 mg/m(2) days 1 to 5, weeks 1 to 4), and cisplatin (20 mg/m(2) days 1 to 5, weeks 1 and 4). Postoperative morbidity was categorized as surgery- and nonsurgery-related morbidity. Survival was calculated by the Kaplan-Meier method. Results were stratified into histology and compared with patients who were operated on only (n = 40). RESULTS: Complete pathological response after preoperative radiochemotherapy was achieved in 22%. An increase in surgery-related morbidity was observed after preoperative radiochemotherapy due to lesion of recurrent nerve (38% versus 12.5%, P = 0.009), as well as a marked difference in pulmonary morbidity (57% versus 37.5%, P = 0.05). The proportion of combined morbidity was increased after preoperative radiochemotherapy (49.4% versus 15%, P = 0.02), which led to a considerable prolongation of postoperative hospital stay (33 versus 21 days median, P = 0.0022). Patients with a longer postoperative hospital stay (>30 days; 43.2%) lived significantly shorter than patients with a shorter postoperative hospital stay (56.8%, P = 0.001). There was no statistical survival benefit in the neoadjuvant treated group. However, calculation of long-term survival revealed a significant survival advantage in patients with squamous cell cancer and a complete pathological response compared with patients without response (median 642 days versus 302, P = 0.026). CONCLUSIONS: Perioperative morbidity was significantly increased after preoperative radiochemotherapy. Long-term survival was clearly affected by the length of postoperative stay. Therefore, we need better patient selection for application of preoperative radiochemotherapy.     

应变力超声弹性成像预测乳腺癌患者新辅助化疗后病理完全缓解

目的评估应变力超声弹性成像(SUE)技术预测乳腺癌患者新辅助化疗(NAC)后病理完全缓解(pCR)的效能。方法收集乳腺癌患者60例,采用SUE评估NAC前肿瘤的弹性评分和弹性应变率比值,记录肿瘤穿刺活检的免疫组化结果,术后病理参照Miller-Panye分级法评估病理反应性,采用Logistic回归分析获得影响NAC后pCR的独立影响因素。绘制不同指标预测pCR结局的ROC曲线,并计算曲线下面积(AUC),Z检验比较不同指标的AUC。结果高弹性评分是pCR的独立影响因素。弹性应变率比值的预测效能最佳,AUC为0.92±0.03,且与Ki-67(0.60±0.08)的AUC比较差异有统计学意义(P0.01);而弹性应变率比值与弹性评分(0.89±0.05)的AUC差异无统计学意义(P=0.36)。结论 SUE评估乳腺癌硬度可预测NAC后pCR结局,在乳腺癌的个体化精准治疗中有重要作用。     

Endoscopic ultrasound: impact on survival in patients with esophageal cancer

BACKGROUND: Esophageal carcinoma is an aggressive malignancy and long-term survival is poor. Endoscopic ultrasound (EUS) is an additional staging modality to assess locoregional extent of this disease. We hypothesized that EUS may improve survival through more effective staging and better optimization of treatment. METHODS: We performed a retrospective review of all patients presenting with esophageal cancer at our institution from 1993 to 2003 (n = 97) and compared outcomes between patients who underwent staging EUS and computed tomography (CT) versus CT alone. Survival was calculated using Kaplan-Meier methods and compared between groups using the log-rank test. Mean survival was compared using analysis of variance (ANOVA) methods. RESULTS: Overall 3-, 6-, and 12-month survival did not differ between the 2 groups (EUS: 92%, 84%, and 80% and CT: 83%, 67%, and 43%, log-rank P = .1), which held true despite stratification by treatment modality (all P >.1). The mean survival for the EUS group was 16 +/- 3 months and for the CT group, 12 +/- 1.5 months (P = .2). Further analysis by stage showed no difference in survival between the 2 groups (all P >.1). However, stage 2A and 3 surgical patients had better survival than nonsurgical patients (both P = .02) irrespective of staging modality. EUS patients were no more likely to receive surgical, neoadjuvant, or definitive chemoradiation than CT patients (all P >.1). CONCLUSIONS: Overall survival as well as survival by stage did not differ between patients who underwent staging via EUS and CT versus CT alone, and patients staged with EUS were not more likely to receive any one intervention. Irrespective of staging modality, stage 2A and 3 patients who underwent surgical intervention had better survival than those who did not receive an operation.