Neoadjuvant and adjuvant chemotherapy in locally advanced bladder cancer

Radical cystectomy has traditionally been considered the gold standard of treatment for patients with muscle-invasive bladder cancer. Following cystectomy a significant portion of patients will develop systemic relapse, usually within 2 to 3 years. Several randomized trials of neoadjuvant and adjuvant chemotherapy suggest that chemotherapy used in combination with primary treatment may improve disease-free survival and permit bladder preservation in selected cases. Whether or not neoadjuvant and adjuvant chemotherapy influence long-term survival remains controversial. This article reviews in depth the various therapeutic options available to patients with locally invasive bladder cancer.     

Venous thromboembolism risk in patients receiving neoadjuvant chemotherapy for bladder cancer

IntroductionThere is limited evidence to inform thromboprophylaxis use for patients receiving neoadjuvant chemotherapy prior to surgery in bladder cancer. We sought to determine the incidence of venous thromboembolism (VTE) in patients receiving neoadjuvant chemotherapy and cystectomy. We also assessed if the Khorana score was associated with VTE risk.MethodsA retrospective cohort study was performed on consecutive patients who received a radical cystectomy for bladder cancer at The Ottawa Hospital between January 2016 and August 2020. Demographic information, chemotherapy data, operative characteristics, VTE and bleeding outcomes were collected from the start of treatment to 90 days postoperative. A Khorana score was calculated for each patient who received neoadjuvant chemotherapy. The primary outcome for this study was the incidence of VTE from the time the patient started treatment with neoadjuvant chemotherapy until 90 days post-cystectomy. Secondary outcomes included risk factors for VTE during neoadjuvant chemotherapy.ResultsAmong 181 radical cystectomy cases during the study period, 123 had muscle-invasive disease and 72 (39.8%) received neoadjuvant chemotherapy. Eighteen (25.0%) patients who received neoadjuvant chemotherapy and radical cystectomy developed a VTE from the start of chemotherapy to 90 days postoperative. Thirteen of the 18 VTEs (72%) occurred while the patient was receiving chemotherapy. In multivariable analysis, the only factor associated with a significantly increased risk of VTE was treatment with neoadjuvant chemotherapy (Relative risk (RR) 3.05, 95% confidence interval [CI] 1.16–8.02; P = 0.02). A higher Khorana score was not associated with an increased risk of VTE in patients who received neoadjuvant chemotherapy (RR = 0.33, 95% CI 0.08–1.28, P = 0.11). One (1.4%) patient had a major bleeding event during neoadjuvant chemotherapy.ConclusionsPatients receiving neoadjuvant chemotherapy and radical cystectomy are at very high-risk of VTE. Prospective studies that assess the benefits and harms of pharmacologic thromboprophylaxis in this population are needed.     

Role of surgery in ovarian cancer: an update

Rupture of an ovarian malignant tumor should be avoided at the time of surgery for an early ovarian cancer. Laparoscopic removal of ovarian cysts should be restricted to patients with preoperative evidence that the cyst is benign. Degree of differentiation is the most important independent prognostic factor in stage I disease and should be used in decisions on therapy in clinical practice and the future FIGO-classification of Stage I. In early ovarian cancer staging adequacy and tumor grade were the only 2 statistical significant prognostic factors for survival in the multivariate analysis of the EORTC ACTION-trial. According to the present data there is no scientific basis to rely only on adjuvant chemotherapy or on optimal staging procedure in medium and high risk stage I ovarian cancer. Primary debulking surgery by a gynecologic oncologist remains the standard of care in advanced ovarian cancer. Optimal debulking surgery should be defined as no residual tumor load. Interval debulking is defined as an operation performed after a short course of induction chemotherapy, usually 2 or 3 cycles. Based on the randomized EORTC-GCG trial, interval debulking by an experienced surgeon improves survival in some patients who did not undergo optimal primary debulking surgery. Based on the GOG 152 data, interval debulking surgery does not seem to be indicated in patients who underwent primarily a maximal surgical effort by a gynecological oncologist. Open laparoscopy is probably the most valuable tool for evaluating the operability primarily or at the time of interval debulking surgery. In retrospective analyses neoadjuvant chemotherapy followed by interval debulking surgery does not seem to worsen prognosis compared to primary debulking surgery followed by chemotherapy. However, we will have to wait for the results of the EORTC-GCG/NCI Canada randomized trial to know whether neoadjuvant chemotherapy followed by interval debulking surgery is as good as primary debulking surgery in some or all stage IIIc and IV patients. The most suitable candidates for secondary debulking surgery are those who had an initial complete response to chemotherapy, a long treatment-free interval (e.g. more than 12 months), and resectable disease (without diffuse carcinomatosis).     

Combined treatment approaches in regionally advanced bladder cancer.

Multimodal therapy for locally advanced bladder carcinoma is being pursued in a wide diversity of protocols at this same time. While a number of innovative approaches are being explored, neoadjuvant and adjuvant chemotherapy in conjunction with cystectomy remains the dominant approach. The M-VAC regimen has become the dominant combination for the treatment of advanced bladder cancer; its use in an adjunctive setting is a logical progression. Although it is capable of effecting a response in the primary bladder lesion in a high percentage of cases, it is still not known whether survival will be enhanced. The use of radiosensitizing cytotoxics in conjunction with neoadjuvant chemotherapy, when combined with external-beam radiotherapy, is a provocative new approach that attempts to achieve both bladder salvage and enhanced patient survival. Completion of well-designed randomized studies will be necessary to determine whether these therapeutic innovations will yield any clinical benefit.     

Neoadjuvant chemotherapy-specific and overall treatment outcomes in patients with cutaneous angiosarcoma of the face with periorbital involvement

BACKGROUND: Recent isolated case reports have suggested a potential role for neoadjuvant chemotherapy in patients with angiosarcoma. The goal of this report was to investigate the overall treatment outcomes and the neoadjuvant chemotherapy-specific outcomes in patients with cutaneous angiosarcoma of the face with periorbital involvement. METHODS: Our tumor database was searched for patients with angiosarcoma and periorbital involvement seen at our institution between 1981 and 2005. RESULTS: Twenty-one patients were identified,15 of whom had neoadjuvant chemotherapy and 6 of whom had a traditional approach of surgery followed by adjuvant therapy.Fourteen of 15 patients who had neoadjuvant chemotherapy had complete clinical response. Neoadjuvant chemotherapy made definitive surgery unnecessary for 9 patients. The median disease-free interval for the neoadjuvant chemotherapy group was 11.8 months (mean, 38.1 months; range, 2.4-239.6 months). Nine of the 15 patients had recurrences. The time from end of treatment to recurrence ranged from 2.6 to 24.5 months (median, 12.7 months).Five of the 6 patients who had primary surgical resection followed by adjuvant radiotherapy and/or chemotherapy had a complete clinical response, and the median disease-free interval was 31.8 months (mean, 35.9 months; range, 2.7-85 months). Two later developed recurrences, one at 2.7 months and the other at 31.8 months after the end of treatment. CONCLUSION: On the basis of this series, the authors conclude that neoadjuvant chemotherapy for periorbital angiosarcoma is a potentially attractive option and in some patients may obviate the need for major surgery, thereby preserving the eye and/or ocular adnexal structures. Given the propensity for recurrence and poor survival, the authors strongly recommend that these patients receive multidisciplinary evaluation and treatment at a major cancer center.     

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??Problems and treatment options of sentinel lymph node in breast cancer WU Di, FAN Zhi-min. Department of Breast Surgery??the First Hospital of Jilin University??Changchun 130021??China
Corresponding author: FAN Zhi-min, E-mail:fanzhimn@163.com
Abstract Sentinel lymph node biopsy (SLNB) has been the primary care in clinically node negative breast cancer. Controversy still surrounds the SLNB of the internal mammary nodes. Because different kinds of tracer have respective feature, surgeons should choose the suitable tracer. All blue lymph nodes and any lymph nodes at the end of a blue lymphatic channel should be removed and designated as SLNs.Clinicians should not recommend ALND for women with early-stage breast cancer who have one or two SLN metastases and will receive breast-conserving surgery with conventionally fractionated whole-breast radiotherapy.Clinicians may offer ALND for women with early-stage breast cancer with nodal metastases found on SNB who will receive mastectomy. For patients who recieved neoadjuvant chemotherapy, SLNB after neoadjuvant chemotherapy is optimal.     

The prognostic value of adjuvant and neoadjuvant chemotherapy in total cystectomy for locally advanced bladder cancer

PURPOSE: Adjuvant chemotherapy and neoadjuvant chemotherapy have been widely used as adjuvant treatment in patients requiring total cystectomy for locally advanced transitional cell carcinoma of the bladder. However, there has been no conclusive evidence that the adjunctive chemotherapy improves survival and no agreement exists concerning what subsets of such patients receive significant benefits from the adjunctive chemotherapy. The study retrospectively sought to clarify these points. PATIENTS AND METHODS: We retrospectively analyzed clinical and pathological records of the 229 patients with transitional cell carcinoma of the bladder who underwent total cystectomy with or without lymph node dissection in our University Hospital from January 1975 to December 1997. Forty-two patients received 1-4 cycles (mean = 1.7) of adjuvant chemotherapy with VPMisCF (n = 19), CisCA (n = 4), MVAC (n = 8), or MEC (Methotrexate, Epirubicin and Cisplatin) (n = 11). Twenty-three patients received 1-4 cycles (mean = 2.1) of neoadjuvant chemotherapy with CisCA (n = 2), MVAC (n = 5), or MEC (n = 16). Using the Kaplan-Meier method, disease-specific survival rate was assessed according to various clinical and pathological factors as well as the administration of adjuvant or neoadjuvant chemotherapy. The generalized-Wilcoxon test was used to evaluate statistical significance (p < 0.05) of survival curves for two or more groups. In addition, a multivariate analysis using the Cox proportional hazards model was performed with respect to multiple clinical and pathological parameters, and treatment modalities. RESULTS: In patients who received neither adjuvant chemotherapy nor radiotherapy, the disease-specific survival rate was significantly lower in those with pT3a and/or more advanced tumors compared with those with pT2 or less advanced tumors. The survival rate in patients with positive lymph node metastasis was significantly lower than that in patients without lymph node metastasis. No apparent survival benefit was noted for those patients who received adjuvant chemotherapy when compared with patients who had pT3a or more advanced tumor and were followed without any adjunctive therapy. In patients with pN2 or more advanced lymph node metastasis, the survival rate of those who received adjuvant CisCA/MVAC/MEC chemotherapy was significantly higher than that those without any adjunctive therapy. Although no apparent survival benefit was observed in patients who received neoadjuvant chemotherapy, the survival rate in patients whose tumor was considered to be down-staged to pT1 or lower was significantly higher than patients who did not receive neoadjuvant chemotherapy and had pT3a or higher pT-stage tumor. The survival rate in patients whose tumor showed clinical partial or complete response by neoadjuvant chemotherapy was also significantly higher than the same control patients. However, the multivariate analysis revealed no significant survival benefit after adjuvant chemotherapy or after neoadjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy after total cystectomy is an acceptable approach in patients with pN2 or higher pN-stage bladder cancer. The significant survival benefit may be obtained who acquired pathological downstaging or partial to complete clinical response after neoadjuvant chemotherapy. To get maximum survival benefit from the present chemotherapeutic regimens and exclude administration of toxic chemotherapeutic agents to unresponsive patients, there should be more reliable markers that give clear information to differentiate tumors that will respond fairly to present chemotherapeutic regimens from tumors that will respond poorly.     

Effectiveness of prehepatectomy intra-arterial chemotherapy for multiple bilobar colorectal cancer metastases to the liver: a clinicopathologic study of peritumoral vasculobiliary invasion

BACKGROUND: Consensus remains to be achieved concerning prehepatectomy neoadjuvant chemotherapy as a treatment strategy for multiple bilobar colorectal liver metastases, in part because the effect of prehepatectomy neoadjuvant chemotherapy has not been determined pathologically. We investigated the efficacy of prehepatectomy intra-arterial chemotherapy for multiple bilobar colorectal cancer metastases to the liver. METHODS: Clinicopathologic data for 37 consecutive patients with > or =5 bilobar liver metastases from colorectal cancer who underwent hepatectomy were analyzed retrospectively with respect to long-term outcome and histological findings in resected liver tumors. RESULTS: In the 15 patients receiving neodadjuvant chemotherapy (NEO+ group), liver metastases progressed in 2 patients, remained stable in 8 patients, responded more than 50% in 4 patients, and responded completely in 1 patient (combined response rate, 33.3%). Overall and hepatic recurrence-free survival tended to be higher in responders than in nonresponders ( P = .053). Microscopic invasion of the portal vein, hepatic vein, and bile ducts near liver tumors was less frequent according to use of neoadjuvant chemotherapy and responsiveness to the therapy (responders, 20.0%; patients not receiving neoadjuvant therapy [NEO-], 72.7%; P < .05). Such microscopic invasion independently predicted hepatic recurrence by multivariate analysis ( P = .011). CONCLUSIONS: A neoadjuvant chemotherapy-associated decrease in microscopic vasculobiliary invasion by metastatic liver tumors was related to clinical response and favorable outcome.     

Role of Surgery in Ovarian Cancer: An Update

Rupture of an ovarian malignant tumor should be avoided at the time of surgery for an early ovarian cancer. Laparoscopic removal of ovarian cysts should be restricted to patients with preoperative evidence that the cyst is benign. Degree of differentiation is the most important independent prognostic factor in stage I disease and should be used in decisions on therapy in clinical practice and the future FIGO-classification of Stage I. In early ovarian cancer staging adequacy and tumor grade were the only 2 statistical significant prognostic factors for survival in the multivariate analysis of the EORTC ACTION-trial. According to the present data there is no scientific basis to rely only on adjuvant chemotherapy or on optimal staging procedure in medium and high risk stage I ovarian cancer. Primary debulking surgery by a gynecologic oncologist remains the standard of care in advanced ovarian cancer. Optimal debulking surgery should be defined as no residual tumor load. Interval debulking is defined as an operation performed after a short course of induction chemotherapy, usually 2 or 3 cycles. Based on the randomized EORTC-GCG trial, interval debulking by an experienced surgeon improves survival in some patients who did not undergo optimal primary debulking surgery. Based on the GOG 152 data, interval debulking surgery does not seem to be indicated in patients who underwent primarily a maximal surgical effort by a gynecological oncologist. Open laparoscopy is probably the most valuable tool for evaluating the operability primarily or at the time of interval debulking surgery. In retrospective analyses neoadjuvant chemotherapy followed by interval debulking surgery does not seem to worsen prognosis compared to primary debulking surgery followed by chemotherapy. However, we will have to wait for the results of the EORTC-GCG/NCI Canada randomized trial to know whether neoadjuvant chemotherapy followed by interval debulking surgery is as good as primary debulking surgery in some or all stage IIIc and IV patients. The most suitable candidates for secondary debulking surgery are those who had an initial complete response to chemotherapy, a long treatment-free interval (e.g. more than 12 months), and resectable disease (without diffuse carcinomatosis).     

Response to Neoadjuvant Chemotherapy Does Not Predict Overall Survival for Patients With Synchronous Colorectal Hepatic Metastases

Objective  We investigated the relation between response to neoadjuvant chemotherapy and overall survival (OS) in patients with colorectal liver metastases (CLM). Background  It has previously been reported that patients with synchronous CLM whose disease progresses while receiving neoadjuvant chemotherapy or who do not receive neoadjuvant chemotherapy experience worse survival than patients whose disease responds to neoadjuvant chemotherapy. Methods  By means of a prospectively maintained surgical database, between 1995 and 2003, we identified 111 patients with a synchronous CLM who received neoadjuvant chemotherapy before hepatic resection. The disease of all 111 patients was deemed resectable, and patients underwent hepatic resection with curative intent. Results  The median OS after liver resection was 62 months, with a median follow-up of 63 months. Median OS was similar between the three study groups classified by response to neoadjuvant chemotherapy (complete or partial response, 58 months; stable disease, 65 months; and disease progression, 61 months; P = .98). By univariate analysis, carcinoembryonic antigen level after liver resection of <5 ng/dL, size of metastatic lesion of ≤5 cm, lymph node–negative primary tumor, and disease-negative margins were associated with improved survival. Patients in the disease progression group had more positive margins and metastases >5 cm in size than patients in the complete or partial response group and the stable disease group. Patients whose tumor progressed but who received postoperative hepatic arterial infusion had a trend toward improved survival compared with those who did not receive hepatic arterial infusion (70% vs. 50% at 3 years, permutation log rank test P = .12). Conclusions  Response to neoadjuvant chemotherapy did not correlate with OS even after controlling for margins, stage of primary tumor, and postoperative carcinoembryonic antigen level. Postoperative salvage treatment may have helped the survival of some patients.     

Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases

The purpose of this study was to compare the treatment and outcome in patients referred for staged re section of synchronous colorectal liver metastases. The records of patients who had undergone colon or rectal resection and were then referred for evaluation of clinically resectable synchronous liver metastases between January 1995 and January 2000 were reviewed. Comparisons were made between patients who did not receive neoadjuvant chemotherapy and had exploratory operations after recovery from colon re section and patients who did receive chemotherapy before liver resection. A total of 106 patients were treated during the 5-year period. Neoadjuvant chemotherapy was given to 52 of the patients; in 29 of them the disease did not progress, but in 17 patients the disease progressed while they were receiving treatment. Median follow-up was 30 months. Patient- and tumor-related variables were similar between groups. Five-year survival was statistically similar between patients who did and those who did not receive neoadjuvant chemotherapy (43% vs. 35%, P = 0.49). Patients within the neoadjuvant group whose dis ease did not progress while they were receiving chemotherapy experienced significantly improved sur vival as compared to patients who did not receive chemotherapy (85% vs. 35%, P = 0.03). In the setting of synchronous colorectal liver metastases, the response to neoadjuvant chemotherapy may be a prognos tic indicator of survival and may assist in the selection of patients for conventional or experimental adju vant therapies. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

Preoperative cholangitis is an independent risk factor for mortality in patients after pancreatoduodenectomy for pancreatic cancer

ObjectivesPreoperative biliary stenting is required for patients with obstructive jaundice from pancreatic adenocarcinoma who are receiving neoadjuvant chemotherapy. While in most patients this approach results in durable biliary drainage, some patients develop cholangitis during neoadjuvant treatment. Further, several studies have shown that preoperative cholangitis in patients with hepatobiliary malignancies can result in substantially unfavorable outcomes. The aim of this study was to evaluate the impact of preoperative cholangitis in patients who underwent pancreaticoduodenectomy after completing neoadjuvant chemotherapy.MethodsParticipants: all adult patients (n = 449) diagnosed with pancreatic adenocarcinoma from January 1st, 2013 to March 31st, 2018 who pursued treatment at the Massachusetts General Hospital were screened. Of these 449 patients, 97 met final inclusion criteria of receiving neoadjuvant chemotherapy with intent to pursue curative surgery. Data were collected via retrospective chart review including baseline characteristics, survival, episodes of preoperative cholangitis, and surgical complications.ResultsIn patients completing successful pancreaticoduodenectomy surgery, preoperative cholangitis is associated with increased mortality (HR 2.67, 95% CI:1.16–6.13). This finding is independent of postoperative outcomes or tumor recurrence rate. The presence of cholangitis did not impact completion of neoadjuvant chemotherapy (92% vs 85%, p = 0.5) or ability to proceed to surgery (76% vs 75%, p = 1.0). Preoperative cholangitis was not associated with postoperative morbidity (42.1% vs 45.1%, p = 1.0).ConclusionsOne episode of cholangitis during neoadjuvant chemotherapy is associated with increased mortality following successful pancreaticoduodenectomy, independent of immediate postoperative outcomes or tumor recurrence. Preoperative cholangitis does not affect ability to pursue neoadjuvant chemotherapy or complete successful surgery. Patients who develop cholangitis during the neoadjuvant chemotherapy treatment phase may reflect a distinct phenotype of patients with PDAC with a complex and more challenging clinical course.     

A comparison of sentinel node biopsy before and after neoadjuvant chemotherapy: timing is important

BACKGROUND: Because neoadjuvant chemotherapy is being used more frequently, the optimal timing of sentinel node biopsy (SNB) remains controversial. We previously evaluated the predictive value of SNB before neoadjuvant chemotherapy in clinically node-negative breast cancer. Our identification rate of the sentinel node among 52 patients before chemotherapy with a mean tumor size of 4 cm was 100%. In this study, we compared the identification rates of SNB before and after neoadjuvant chemotherapy and evaluated the false-negative rate of SNB after chemotherapy. METHODS: A retrospective institutional database review identified 36 women who underwent SNB after neoadjuvant chemotherapy for breast cancer from 1999 to 2004. The initial clinical tumor size and lymph node status, SNB pathology, axillary lymph node dissection pathology, and residual pathologic tumor size were reviewed. RESULTS: Sixteen of 36 patients had a clinically negative axilla before neoadjuvant therapy. SNB after neoadjuvant therapy was successful in 29 patients (80.6%), although 7 patients did not map (19.4%). Six of the 7 patients who failed to map had a clinically positive axilla initially. Axillary disease was found in 6 of 7 of these patients at dissection (85.7%). Of the 29 patients who mapped successfully, 13 (45%) were SNB negative, and 16 (55%) were SNB positive. Of the 13 SNB-negative patients, 2 had a positive axillary lymph node dissection, yielding a false-negative rate of 11%. Thirteen patients who mapped had a clinically positive axilla before therapy (45%). Of the 11 patients with true-negative SNBs, 7 (64%) were clinically node negative at presentation. The initial tumor sizes on examination ranged from 2 to 9 cm (mean, 5.0 cm), and residual pathologic tumor sizes ranged from 0 to 6 cm (mean, 1.8 cm). Failure to map correlated with a clinically positive axilla at presentation (100% vs 45%) but did not correlate with initial tumor size. CONCLUSIONS: Sentinel node identification rates are significantly better when mapping is performed before neoadjuvant chemotherapy (100% vs 80.6%), with failure to map correlated with clinically positive nodal disease at presentation and residual disease at axillary lymph node dissection. Among patients who map successfully after chemotherapy, the false-negative rate is high (11%). Given these findings, we currently recommend SNB before neoadjuvant chemotherapy for clinically node-negative patients, and raise concerns about the use of SNB after neoadjuvant therapy in patients with an initially clinically positive axilla.     

乳腺癌前哨淋巴结活检的若干问题和处理方案

前哨淋巴结活检（SLNB）已成为腋窝淋巴结临床阴性早期乳腺癌的首选腋窝手术方式,但其适应证范围已有所扩大。内乳淋巴结是否需要SLNB,尚存争议。不同示踪剂有各自的特点,应用时需要根据各临床中心的实际情况予以选择。寻找前哨淋巴结（SLN）时,原则上要循着色淋巴管解剖至腋窝寻找SLN。对于符合美国外科医师协会肿瘤学组（ACOSOG）Z0011试验入组标准的存在1～2枚SLN转移的病例不需腋窝淋巴结清扫（ALND）。仅行全乳切除的病例,如果SLN阳性,则需要进行腋窝淋巴结清扫。对于接受新辅助治疗病人接受SLNB的时机,目前认为在新辅助治疗后进行为好。     

Multimodality preoperative treatment for advanced stage IV (MO) cancer of the head and neck

Sixty-three patients with advanced unresectable squamous cell carcinoma of the head and neck were treated with a combination of chemotherapy, radiation, and surgery. We observed a 75% response to neoadjuvant chemotherapy. The 5-year survival rate for all 63 patients was 20%, and only 3 patients were alive at 8 years. The 5-year survival rate for patients who completed the treatment plan and received chemotherapy, radiation, and surgery was 43% compared with 20% for those who had chemotherapy and radiation but refused surgery. Development of a second primary cancer was the cause of death in 62% of the patients who survived more than 24 months.     

Treatment and prognosis for synchronous multifocal osteosarcoma in 42 patients

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure. After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site. The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour.     

Neoadjuvant systemic therapy and the surgical management of breast cancer

Neoadjuvant chemotherapy is standard management for women who have locally advanced or inflammatory breast cancer, but can be applied to all women who may require postoperative chemotherapy for early-stage breast cancer. Disease-free survival and overall survival are equivalent between patients treated with neoadjuvant chemotherapy and patients treated with the same regimen postoperatively. Preoperative chemotherapy can offer women less morbid surgical treatment by down-staging both the primary breast tumor and axillary metastases. Finally, response to chemotherapy can inform clinicians of the chemosensitivity of the tumor, and can predict long-term outcome for women who have breast cancer.     

Strategy for the treatment of unresectable hepatoblastoma: neoadjuvant chemotherapy followed by delayed primary operation or liver transplantation

We present our experience in using neoadjuvant regional and systemic chemotherapy together with surgical resection as a strategy for the treatment of unresectable hepatoblastoma. Neoadjuvant chemotherapy was given prior to surgical treatment in six children with unresectable hepatoblastoma. Furthermore, the neoadjuvant chemotherapy was intensified according to response to the initial treatment. Surgical resection was performed when the tumor was judged to be resectable. The adjuvant chemotherapy was given after delayed primary operation. Five of six children receiving neoadjuvant chemotherapy responded to the treatment and subsequently received delayed primary operation or living donor liver transplantation. All five children who had successful surgery have completed treatment and show no evidence of disease to date (27-115 months after surgery). It is concluded that neoadjuvant chemotherapy given as a combination of regional and systemic chemotherapy was effective for tumor reduction in cases with early stage or stage III disease. Also, to increase the cure rate of children with localized disease that was still unresectable after chemotherapy, living donor liver transplantation, which offers some advantage in timing of transplant compared with cadaveric liver transplantation, seems to be a possible procedure.     

The developing clinical problem of chemotherapy-induced hepatic injury

Chemotherapy is being administered to an increasing number of patients with colorectal liver metastases (CRLM), whether they have resectable disease or not. Although this may be appropriate to downstage patients with unresectable disease, and offers theoretical advantages to those who have resectable disease, there is a price to be paid in the development of chemotherapy-induced hepatic injuries (CIHI). These include chemotherapy-associated fatty liver diseases and sinusoidal injuries. The main chemotherapeutic agents currently used in the adjuvant setting for colorectal carcinoma, and the neoadjuvant treatment of CRLM include 5-flurouracil, oxaliplatin and irinotecan, and while there are non-specific and overlapping injury profiles, oxaliplatin does appear to be primarily associated with sinusoidal injury and irinotecan with steatohepatitis. In this review, the rationale for administering chemotherapy to patients with CRLM is presented, and the problems this brings are outlined. The specific injury patterns will be detailed, as well as the data correlating specific chemotherapy regimens to these injury patterns. Finally, the clinical outcomes of patients with CRLM who undergo neoadjuvant chemotherapy followed by hepatic resection will be considered. The need for methods to identify patients at risk of CIHI and to recognize established CIHI prior to surgery will be emphasized.     

TopoⅡ、MRP和GST-π在食管胃交界部腺癌中的表达及与新辅助化疗疗效的关系

目的探讨TopoⅡ、MRP和GST-π5在进展期食管胃交界部腺癌新辅助化疗疗效中的预测价值。方法对72例食管胃交界部腺癌患者行SOX方案新辅助化疗,以RECIST 1.0评价标准评价疗效。用免疫组化方法检测化疗前3种蛋白的表达情况,并分析其与化疗疗效的关系。结果年龄和病理类型与化疗敏感性无关(P0.05)。本组72例患者中新辅助化疗有效率为48.6%,其中5例达病理完全缓解,6例进展。患者肿瘤标本中3种蛋白的表达情况:TopoⅡ、MRP和GSTπ的阳性率分别为73.6%、34.7%和40.3%。TopoⅡ、MRP和GST-π的表达与化疗敏感性无关(P0.05)。结论 TopoⅡ、MRP和GST-π的表达与食管胃交界部腺癌新辅助化疗的疗效无关,尚不能作为预测SOX方案疗效的指标。