Surgical Resection after Downsizing Chemotherapy for Initially Unresectable Locally Advanced Biliary Tract Cancer: A Retrospective Single-center Study

Background

Surgical resection is the only method for curative treatment of biliary tract cancer (BTC). Recently, an improved efficacy has been revealed in patients with initially unresectable locally advanced BTC to improve the prognosis by the advent of useful cancer chemotherapy. The aim of this study was to evaluate the effect of downsizing chemotherapy in patients with initially unresectable locally advanced BTC.

Methods

Initially unresectable locally advanced cases were defined as those in which therapeutic resection could not be achieved even by proactive surgical resection. Gemcitabine was administered intravenously once a week for 3 weeks followed by 1 week’s respite. Patients whose disease responded to chemotherapy were reevaluated to determine whether their tumor was resectable.

Results

Chemotherapy with gemcitabine was provided to 22 patients with initially unresectable locally advanced BTC. Tumor was significantly downsized in nine patients, and surgical resection was performed in 8 (36.4%) of 22 patients. Surgical resection resulted in R0 resection in four patients and R1 resection in four patients. Patients who underwent surgical resection had a significantly longer survival compared with those unable to undergo surgery.

Conclusions

Preoperative chemotherapy enables the downsizing of initially unresectable locally advanced BTC, with radical resection made possible in a certain proportion of patients. Downsizing chemotherapy should be proactively carried out as a multidisciplinary treatment strategy for patients with initially unresectable locally advanced BTC with the aim of expanding the surgical indication.     

Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer

OBJECTIVE: To evaluate, in the ongoing Early Prostate Cancer (EPC) trial programme, the efficacy and tolerability of bicalutamide 150 mg once daily in addition to standard care for localized or locally advanced, nonmetastatic prostate cancer. PATIENTS AND METHODS: The EPC programme comprises three randomized, double-blind, placebo-controlled trials designed for combined analysis. Following standard care, 8113 men with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N+) prostate cancer (all M0) received oral bicalutamide 150 mg once daily or oral placebo. The primary endpoints were progression-free survival (PFS) and overall survival. RESULTS: The large EPC trial programme is defining men who benefit or do not from early or adjuvant antiandrogen therapy. At a median follow-up of 7.4 years, in localized disease there is no benefit to PFS by adding bicalutamide to standard care, and there is a trend (hazard ratio, HR, 1.16; 95% confidence intervals, CI, 0.99-1.37; P = 0.07) towards decreased survival in patients otherwise undergoing watchful waiting. However, in locally advanced disease, bicalutamide significantly improved PFS irrespective of standard care. Bicalutamide significantly improved overall survival in patients receiving radiotherapy (HR 0.65; 95% CI 0.44-0.95; P = 0.03); this was driven by a lower risk of prostate cancer-related deaths. Bicalutamide produced a trend towards improved overall survival in patients with locally advanced disease otherwise undergoing watchful waiting (HR 0.81; 95% CI 0.66-1.01; P = 0.06). No survival difference was evident in the prostatectomy subgroup. CONCLUSIONS: This ongoing programme is clarifying the role of early or adjuvant antiandrogen therapy in prostate cancer. Patients with localized disease do not appear to derive clinical benefit from added bicalutamide. However, adding bicalutamide 150 mg to standard care provides significant clinical benefits in patients with locally advanced prostate cancer, irrespective of primary therapy.     

Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program

PURPOSE: We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer. MATERIALS AND METHODS: This international program consists of 3 ongoing, randomized, double-blind, placebo controlled clinical trials (trials 23, 24, and 25). Men with localized or locally advanced (T1-T4, Nx/N0, M0) prostate cancer were randomized to receive 150 mg. bicalutamide daily or placebo, in addition to standard care with radical prostatectomy, radiotherapy or watchful waiting. Primary end points are time to objective progression and overall survival. In this first analysis data from the trials were combined in a single overview analysis according to protocol. RESULTS: Data are available for 8,113 patients (4,052 randomized to bicalutamide, 4,061 to standard care alone) at a median followup of 3.0 years. Treatment with bicalutamide provided a highly significant reduction of 42% in the risk of objective progression compared with standard care alone (9.0% versus 13.8%, hazards ratio 0.58; 95% confidence interval 0.51, 0.66; p <0.0001). The overall result was reflected in 2 of the 3 trials (trials 24 and 25) with trial 3 (trial 23) showing a nonsignificant difference at this time. Reductions in the risk of disease progression were seen across the entire patient population, irrespective of primary treatment or disease stage. Overall survival data are currently immature and longer followup will determine if there is also a survival benefit with bicalutamide. The most frequently reported side effects of bicalutamide were gynecomastia and breast pain. CONCLUSIONS: Immediate treatment with 150 mg. bicalutamide daily, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with localized or locally advanced prostate cancer. This benefit must be balanced with the morbidity associated with long-term hormonal therapy. Followup is ongoing to determine potential survival benefits of this treatment approach.     

Is There a Role for Cholecystectomy in Gallbladder Carcinoma Discovered to be Unresectable for Cure at Laparotomy?

BACKGROUND: Palliative operative resection in patients with locally advanced cancer of the gallbladder (GBC) found not to be amenable to radical resection for cure at exploration has received little attention. This article evaluates the benefits, if any, of cholecystectomy with biliary drainage in such patients. METHODS: Available records of locally advanced but nonmetastatic GBC patients treated in the Department of Surgical Oncology, B.H.U., Varanasi, India, during the last 8 years were retrospectively reviewed. Of these, 30 patients (group I) with GBC (T(3-4),N(0-1),M(0)) treated with cholecystectomy +/- biliary bypass were selected and compared with equal number of controls matched for age (+/-5 years), sex, histopathology, stage, residence, and postoperative chemotherapy who underwent biopsy +/- biliary bypass only (group II) followed by chemotherapy during the same period. Survival rates were calculated by using Kaplan-Meier curves. Follow-up ranged from 1-15 months. RESULTS: The median survival was 7 and 2 months for groups I and II (P < 0.0001), respectively. The 30-day postoperative mortality and morbidity was 3% vs. 12% and 13% vs. 16% in groups I and II, respectively. CONCLUSIONS: Results suggest that a better median survival can be achieved after cholecystectomy in locally advanced unresectable GBC compared with only bypass and biopsy procedures. These findings may justify a palliative cholecystectomy in selected patients with locally advanced GBC.     

Neoadjuvant therapy of stage III non-small cell lung cancer]

Locally advanced stage III disease constitutes 30 to 40% of the entire group of non-small cell lung cancer. Surgery is the only curable modality in this stage disease, but resection rate is less than 40%. Even in completely resected patients 5-year survival is only 30%. Several reports have evaluated postoperative chemotherapy and radiotherapy. Prospective randomized studies, however, have failed to demonstrate a survival advantage from adjuvant therapy. Neoadjuvant therapy is under investigation in attempt to improve survival of stage III patients. Preliminary data show that neoadjuvant therapy could increase resection rate and improve survival with moderate toxicities. However, there are many problems in study design such as the use of single-arm studies with short duration of follow-up, lack of accurate staging of selected patients and no precise definitions of resectability for stage III disease. Therefore, there is an urgent need for well designed randomized trial to confirm whether neoadjuvant therapy offers a survival advantage on locally advanced stage III disease.     

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??Comprehensive standard treatments of gallbladder cancer: What can we learn form NCCN guidelines? LIANG Ting-bo. Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
Abstract Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy. Surgery reserves the only potential cure for GBC. However, patients with advanced GBC don’t benefit much form surgery. The NCCN guideline for GBC has offered evidence-based guidance in countering such fatal disease. According to the latest NCCN guideline, standard preoperative assessments, proper surgical procedures and individualized adjuvant therapies are pivotal in improving patients’ survival.     

Gemcitabin/Cisplatin vs. MVAC

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.     

Perioperative therapy for esophageal cancer

Traditionally, surgery is considered the best treatment for esophageal cancer in terms of locoregional control and long-term survival, but survival after surgery alone for locally advanced esophageal cancer is not satisfactory. A multidisciplinary approach that includes surgery, radiotherapy, and chemotherapy, alone or in combination, has been developed to improve the prognosis. Multiple clinical trials have addressed the preferred treatment strategy, such as neoadjuvant or adjuvant and chemotherapy, radiotherapy, or chemoradiotherapy, in managing locally advanced esophageal cancer. In this review, we provide an update on treatment strategies for locally advanced esophageal cancers. Recent studies indicate that neoadjuvant chemoradiotherapy or chemotherapy has a survival benefit over surgery alone in this patient group. Neoadjuvant chemoradiotherapy is an accepted standard of care in the United States while neoadjuvant chemotherapy is regarded as standard treatment in Japan and the United Kingdom. The standard treatment differs among countries because two large randomized controlled trials that evaluated the effectiveness of neoadjuvant chemotherapy reported conflicting results and no trial has made a comparison between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy directly. Future trials in locally advanced esophageal cancer should focus on identifying the optimum strategy and its regimen and aim to minimize treatment toxicities and effects on quality of life.     

程序性细胞死亡蛋白-1抑制剂治疗晚期胆道恶性肿瘤疗效和预后因素分析

目的 评估程序性细胞死亡蛋白-1（PD-1）抑制剂治疗晚期胆道恶性肿瘤（BTC）的有效性和安全性。方法 回顾性分析2017年1月至2020年1月92例海军军医大学东方肝胆外科医院胆道一科接受PD-1 抑制剂治疗的晚期BTC病人临床资料、治疗效果、疾病无进展生存期（PFS）、总生存期（OS）和药物不良反应等资料,探讨不同治疗方案的临床疗效及可能相关的预后因素。结果 92例病人中,胆囊癌（GBC）31例、肝内胆管癌（ICC）34例、肝外胆管癌（ECC）27例。PD-1抑制剂治疗后6个月的客观缓解率（ORR）和疾病控制率分别为（DCR）17.4％和40.2％,其中GBC（25.8%）和ICC（23.5%）病人的ORR高于ECC（0）病人。92例病人的中位PFS为4.0个月,中位OS为10.0个月。联合靶向治疗组中位PFS及OS大于单药组（分别为5.0 个月vs. 2.5个月,P=0.007;11.0 vs. 7.5个月,P=0.005）,差异有统计学意义;联合化疗组中位PFS 及OS大于单药组,但差异无统计学意义（分别为3.2 个月vs. 2.5个月,P=0.227;10.0个月 vs. 7.5个月,P=0.114）;联合靶向治疗组中位PFS 及OS与联合化疗组相比,差异无统计学意义（分别为5.0个月vs. 3.2个月,P=0.101;11.0 vs. 10.0个月,P=0.254）。6例病人出现3级及以上免疫相关的不良反应。结论 对于晚期BTC病人,PD-1抑制剂联合靶向治疗的效果优于单药治疗;与ECC相比,GBC和ICC病人更可能从PD-1抑制剂治疗中获益。     

Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer: final results from the bicalutamide Early Prostate Cancer programme at a median follow-up of 9.7 years

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To evaluate the efficacy and tolerability of bicalutamide 150 mg once‐daily as immediate hormonal therapy in patients with prostate cancer or as adjuvant to radical prostatectomy or radiotherapy.

PATIENTS AND METHODS

In all, 8113 patients with localized (T1‐2, N0/Nx) or locally advanced (T3‐4, any N; or any T, N+) prostate cancer (all M0) were enrolled in three complementary, double‐blind, placebo‐controlled trials. Patients were randomized to receive standard care plus either oral bicalutamide 150 mg once‐daily or oral placebo. Primary endpoints were progression‐free survival (PFS) and overall survival (OS). Data were collated from individual trials and evaluated in a combined analysis.

RESULTS

Overall, at a median follow‐up of 9.7 years, bicalutamide significantly improved PFS (hazard ratio 0.85, 95% confidence interval 0.79–0.91; P= 0.001). Compared with placebo there was no difference in OS (hazard ratio 1.01, P= 0.77). Patients who derived benefit from bicalutamide in terms of PFS were those with locally advanced disease, with OS significantly favouring bicalutamide in patients with locally advanced disease undergoing radiotherapy (P= 0.031). Patients with localized disease showed no clinically or statistically significant improvements in PFS; there was a survival trend in favour of placebo in patients with localized disease undergoing watchful waiting (P= 0.054). The overall tolerability of bicalutamide was consistent with previous analyses, with breast pain (73.7%) and gynaecomastia (68.8%) the most frequently reported adverse events in patients randomized to bicalutamide.

CONCLUSIONS

Bicalutamide 150 mg, either as monotherapy or adjuvant to standard care, improved PFS in patients with locally advanced prostate cancer, but not in patients with localized disease. A pre‐planned subset analysis showed a benefit for OS in patients with locally advanced disease undergoing radiotherapy. Bicalutamide 150 mg might represent an alternative for patients with locally advanced prostate cancer considering androgen‐deprivation therapy.     

Prospective randomized trial comparing flutamide as adjuvant treatment versus observation after radical prostatectomy for locally advanced, lymph node-negative prostate cancer

OBJECTIVE: To assess the efficacy and the tolerability of flutamide as adjuvant treatment after radical prostatectomy for locally advanced, lymph node-negative prostate cancer. METHODS: Men with locally advanced, lymph node-negative prostate cancer were randomized after radical prostatectomy to receive either flutamide 750mg daily or no adjuvant treatment. Recurrence-free and overall survival were the study end points. Recurrence was defined as a PSA value greater than 5ng/ml or two values greater than 2ng/ml more than three months apart with increasing tendency or three values greater than 1ng/ml more than three months apart with increasing tendency or any clinical recurrence. RESULTS: 309 patients (157 in the control arm and 152 in the flutamide arm) were eligible for efficacy analysis. The median follow-up was 6.1 years. Recurrence-free survival was better in the flutamide group ( P=0.0041), there was, however, no detectable difference in overall survival ( p=0.92 ). Moreover, there was a considerable toxicity reported in the flutamide group. CONCLUSION: Although having some effect on disease recurrence, adjuvant flutamide treatment does not improve median-term overall survival after radical prostatectomy for locally advanced, lymph node-negative prostate cancer.     

晚期胆囊癌的外科治疗

目的：提高晚期胆囊癌的生存率及治疗效果。方法：对1990年1月至2001年6月我科手术治疗的80例晚期胆囊癌患者的资料进行回顾性分析。其中71例伴有阻塞性黄疸，15例扪及腹部包块，对已润周围器官及胆管但尚无肝脏广泛转移或远处转移的39例晚期胆囊癌进行了扩大根治术（其中11例合并胰十二指肠切除术），结果：该39例术后丰活8－37个月（平均存活18．1个月），1，2，3年生存率分别为43．6％，20．5％及5．1％，对另41例已有肝脏转移或腹膜种植转移的晚期胆囊癌仅行姑息性手术，术后随访除1例存活19个月外，其余均于1年内死亡，结论：对晚期胆囊癌的治疗应尽可能地行扩大根治术。     

从NCCN指南看胆囊癌的规范化综合治疗

胆囊癌虽发病率较低但恶性程度很高。手术为根治胆囊癌的惟一可能手段,但进展期肿瘤的手术效果较差。美国国家综合癌症网络（NCCN）指南的推陈出新为临床医生诊治胆囊癌提供了规范化的循证医学支持。根据NCCN指南,规范的术前评估、合理的手术方式及个体化的辅助治疗是延长胆囊癌病人生存期的关键。     

Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup

PURPOSE: Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration. MATERIALS AND METHODS: Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio. RESULTS: A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup. CONCLUSIONS: Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.     

Case report: Irreversible electroporation for locally advanced pancreatic cancer

IntroductionFor patients with pancreatic adenocarcinoma who are not candidates for surgical resection, long-term survival is poor, even with currently available systemic and radiation therapy options. However, for those with locally advanced disease who do not have distant metastasis, locoregional control of the tumor has the potential to improve long-term outcomes. A newly developed technology, irreversible electroporation, has advantages over traditional thermal ablation with unresectable cancers in this location.Presentation of caseIn our case report, we describe the first patient treated with irreversible electroporation at our institution for locally advanced pancreatic cancer. The patient is a 63-year-old man who had a partial response to standard chemotherapy and radiation, but was found on operative assessment to have persistently unresectable disease. He therefore underwent irreversible electroporation to the pancreatic mass. His postoperative course was complicated by delayed gastric emptying and wound infection. Three months after surgery, he had no evidence of distant or recurrent disease.DiscussionIrreversible electroporation for locally advanced pancreatic cancer is an emerging technique which attempts to improve local control of locally advanced, non-metastatic pancreatic cancer. Early data have demonstrated the potential for improved long-term survival in these patients, although further studies are needed to confirm safety and efficacy of this technique.ConclusionWhile there is a positive outlook for the use of irreversible electroporation for locally advanced pancreas cancer, there remain some uncertainties surrounding this therapy, which underscores the importance of future research in this area.     

Modified FOLFIRINOX for unresectable locally advanced or metastatic gallbladder cancer,a comparison with GEMOX regimen

BackgroundThe first-line chemotherapy regimen for advanced gallbladder cancer (GBC) is gemcitabine plus platinum (GP), despite its efficacy is limited. The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine plus oxaliplatin (GEMOX) as the first-line chemotherapy for unresectable locally advanced or metastatic GBC.MethodsThe data of patients with unresectable locally advanced or metastatic GBC, who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, were retrieved. This retrospective study evaluated the clinical characteristics, survival outcomes and adverse events.ResultsA total of 44 patients (n=25 in mFOLFIRINOX, n=19 in GEMOX) were included. There were no significant differences between groups in baseline characteristics. The median progression free survival (mPFS) was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group [P=0.021; hazard ratio (HR), 0.499; 95% CI, 0.266 to 0.937]. The median overall survival (mOS) was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group (P=0.019; HR, 0.471; 95% CI, 0.239 to 0.929). Disease control rate (DCR) was 76.0% in the mFOLFIRINOX group and 47.4% in the GEMOX group (P=0.051). The rate of grade 3–4 adverse events was 48% in the mFOLFIRINOX group and 36.8% in the GEMOX group (P=0.459). The incidence of grade 3–4 neutropenia and diarrhea were more common in the mFOLFIRINOX group, while the incidence of grade 3–4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group.ConclusionsmFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC, and the results need to be further verified by prospective clinical studies.     

Chemotherapy in the post-MVAC era: the case for adjuvant chemotherapy

Radical cystectomy for muscle invasive and locally advanced bladder cancer is the standard treatment modality in most of the Western industrialised countries. Rates of perioperative mortality from radical cystectomy have decreased to less than 2% over the past two decades due to advances in surgical technique and perioperative care. However, at least 40% of patients with pT3 bladder cancer and 70% of patients with lymph node-positive disease develop tumour recurrence after radical treatment within the first 5 years when treated with radical cystectomy alone. After the efficacy of combination chemotherapy for metastatic urothelial cancer using methotrexate, vinblastine, adriamycin and cisplatin (MVAC) was first described in 1985, several cisplatin-based systemic regimens have been investigated as adjunctive treatment before or after therapy for locally advanced bladder cancer by radical surgery or radiation therapy. Three randomised studies have reported superior results of postoperative adjuvant systemic chemotherapy compared to radical cystectomy alone for locally advanced bladder cancer. All three studies demonstrated a significant survival benefit for bladder cancer patients receiving adjuvant combination therapy. Studies have been criticised for small patient numbers and statistical shortcomings. New effective antineoplastic agents, such as paclitaxel and gemcitabine, have evolved during the past decade as promising substances for the treatment of urothelial cancer. This article reviews adjuvant studies from the era of MVAC combination chemotherapy, as well as contemporary studies that discuss new antineoplastic agents for systemic adjuvant chemotherapy of locally advanced bladder cancer.     

Current status of liver transplantation for hepatocellular cancer

The incidence of hepatocellular cancer is increasing in the United States and is one of the most common cancers worldwide. Traditionally, the gold standard treatment for hepatocellular cancer has been surgical resection, but most patients were not suitable candidates due to advanced disease. Other treatments include locally ablative techniques (cryosurgery, radiofrequency ablation and various injection therapies), chemotherapeutic options and rarely, radiation therapies. In the 1980s, liver transplant emerged as the treatment of choice for end-stage liver disease and also became an option for patients with hepatocellular cancer. When comparing liver transplant with resection in retrospective studies, liver transplant patients had better survival and reduced recurrence. However, not all patients with hepatocellular cancer will be candidates for liver transplant. Size, stage, and histological grade of tumor all affect prognosis after transplant. Use of chemotherapeutic treatments and locally ablative techniques may be beneficial prior to liver transplant, but larger controlled studies are needed. Liver transplant is the most effective treatment for hepatocellular cancer in the subgroup of smaller tumors, but ultimately we are limited by the number of available donors. Future goals in this area include increasing the donor pool and determining optimal management to allow patients to wait for an appropriate donor.     

The role of adjuvant chemotherapy for locally advanced bladder cancer

The incidence of locally advanced bladder cancer is estimated at 5 new cases per 100,000 of the population annually in North America and most European countries. Radical cystectomy for muscle-invasive organ-confined tumors and locally advanced disease, which is defined as extravesical tumor growth or involvement of regional lymph nodes, is the preferred treatment in Japan, the United States, and in some countries of Europe. The clinical outcome of radical cystectomy has improved remarkably over the past 20 years as a result of advances in operative technique and perioperative care. Nevertheless, at least 50% of patients with invasive bladder cancer are expected to develop progressive disease within the first 2?years when treated with radical cystectomy alone. In order to improve the fate of muscle-invasive and locally advanced disease, the administration of additional therapy to definite treatment has been studied in various forms, such as neoadjuvant and adjuvant systemic chemotherapy as well as combined radio-chemotherapy. Prolonged progression-free survival for patients suffering from locally advanced bladder cancer by administration of adjuvant systemic chemotherapy has been suggested by three randomized studies, published by Skinner, Freiha and Stöckle since 1991. These studies demonstrated a disease-free survival benefit of 17–50% within the first 3–5?years when applying adjuvant systemic chemotherapy after radical cystectomy. Patients who most likely benefit from adjuvant chemotherapy are those with limited node-positive disease, extravesical tumor, and direct invasion into adjacent viscera, such as prostate, uterus, or vagina. This review will summarize past, current, and future aspects of systemic adjuvant chemotherapy for transitional cell carcinoma of the bladder.     

Postoperative adjuvante Chemoradiotherapie beim Hochrisikomagenkarzinom

Gastric cancer is a common cancer worldwide with a high mortality rate. Despite curative intent resection, locoregional failure as a frequent site of recurrence is responsible in part for this high mortality. Many attempts have been made to decrease the risk of recurrence after resection. Studies involving postoperative chemotherapy as a single modality have not clearly demonstrated benefit. Similarly, most studies of postoperative radiation therapy have not clearly shown an improvement in overall survival. Recently, however, a USA Intergroup study indicated a survival advantage for chemoradiation therapy compared to surgery alone for patients with locally advanced gastric cancer. “Intergroup-116” is a large-scale randomized trial designed to evaluate the role of adjuvant chemotherapy plus radiotherapy following curative intent gastric resection. The data from this study demonstrate a survival benefit with adjuvant chemoradiation that may in large part be due to better locoregional control. While many patients had a less then adequate lymph node dissection, survival was not associated with the type of lymph node dissection performed. Toxicity was acceptable. “Intergroup-116” indicates that postoperative chemoradiation should be considered as a standard care option for patients with locally advanced gastric cancer. Future studies should evaluate potentially more effective systemic therapy, molecularly-directed treatment, and possibly, whether or not more formal lymph node dissections would obviate the need for radiation.