Correlation between GP-170 expression,prognosis, and chemoresistance of superficial bladder carcinoma

Purpose To study GP-170 in superficial bladder cancer at initial diagnosis and at recurrence and to evaluate if intravesical chemoprophylaxis modifies the expression of GP-170 in tumor recurrences.Materials and methods GP-170 was retrospectively assessed in 160 patients affected by primary superficial transitional cell carcinoma of the bladder and followed for up to 10 years. Eighty-four patients (52.5%) recurred after transurethral resection (TUR). Adjuvant intravesical chemotherapy after TUR was adopted in 52 patients. The correlations between GP-170 and G-grade, T-category, risk of recurrence and of progression, and adoption of adjuvant intravesical chemotherapy were investigated. The correlations between variations in grade and stage at recurrence and modifications in GP-170 expression were also studied.Results No significant correlation between GP-170 expression and G-grade and T-category was found. A significant correlation was detected between GP-170 expression and recurrence (P=0.0383). It showed a biphasic pattern, i.e., tumors that did not express GP-170 had a higher recurrence rate, but high GP-170 levels were also associated with an increasing risk of recurrence. Intravesical chemotherapy did not induce significative variations in GP-170 expression. No correlation was found between progression and GP-170.Conclusion GP-170 seems to be an independent prognostic factor for recurrence in superficial bladder tumors. A negative GP-170 pattern and high levels of GP-170 are associated with an increasing risk of recurrence but have no impact upon progression. In our experience, GP-170 is neither induced nor modified by intravesical chemotherapy, although it might represent a factor of chemoresistance when strongly expressed.This study was supported by a grant of the Associazione Italiana per la Ricerca sul Cancro (AIRC)     

Perioperative chemotherapy for bladder cancer

The presence of occult micrometastases at the time of radical cystectomy leads to both distant and local failure in patients with locally advanced transitional cell carcinoma of the bladder. Cisplatin-based chemotherapy produces responses in 40-60% of patients with metastatic bladder cancer. Perioperative administration of chemotherapy in bladder cancer patients theoretically can impart the same survival benefits demonstrated in patients with breast, lung and colon cancer. Both neoadjuvant and adjuvant therapy have been evaluated in patients with locally advanced bladder cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power to detect meaningful clinical answers, as well as experimental arms utilizing inadequate chemotherapy. Two randomized clinical trials have demonstrated a survival benefit for neoadjvuant CMV (Cisplatin, Methotrexate, Vinblastine) or MVAC (methotrexate, vinblastine, adriamycin, cisplatin). The aggregate of available evidence suggests that neoadjuvant cisplatin-based combination chemotherapy should be considered a standard of care for patients with muscle-invasive/locally advanced operable bladder cancer. However, some physicians prefer to defer chemotherapy until after surgery, when pathologic stage is defined, as well as the risk of relapse. In patients who are either unfit for or refuse radical cystectomy, neoadjuvant chemotherapy with or without radiation can render bladder preservation possible in patients who attain pathologic major response.     

Intravesical adjuvant chemotherapy for superficial bladder cancer -- results of a survey in Saxony

For patients with superficial bladder cancer, adjuvant intravesical chemotherapy or immunotherapy with Bacillus Calmette-Guerin (BCG) is recommended in national and international guidelines. We analyzed whether the recommended therapeutic regimens are used in daily urological practice. Questionnaires concerning the adjuvant intravesical therapy were sent to 152 urologists in the German Federal State of Saxony. Of the surveyed physicians, 134 practiced in an outpatient medical facility and 18 in a hospital. Of the questionnaires, 73 (48.02 %) were returned and evaluated. An adjuvant intravesical therapy after transurethral bladder tumor resection was performed in every second patient (median value 50.07 %). The majority of the urologists (79.4 %) treated the bladder tumors with intravesical chemotherapy or BCG depending on tumor stage and grade of malignancy. Chemotherapeutic agents or BCG was exclusively used in 13.6 % and 4.1 % of treated patients, respectively. Chemotherapeutic agents were predominantly applied up to the primary tumor stage T1 and malignancy grade G2. In cases with recurrent T1 bladder tumors of G2 or higher grade of malignancy, BCG was the main agent for intravesical treatment. In patients with recurrent T1G3 tumors, the majority of urologist (57.1 %) preferred another therapeutic regimen than intravesical instillation. Only 23.2 % of the urologists believed that intravesical BCG is superior to chemotherapeutic agents. These data demonstrate that adjuvant intravesical instillation with chemotherapeutic agents and BCG is well established in urological practice. In contrast to the recommendations of national and international guidelines, chemotherapeutic agents are more frequently used in cases with a high risk of progression.     

Intravesical Chemotherapy: An Update—New Trends and Perspectives

More than 90% of all malignant bladder tumours are transitional cell carcinomas (TCC). Superficial TCC of the bladder is characterized by a high risk of recurrence (30–85%) after transurethral resection (TUR) of the initial tumour. Despite this high risk of recurrence, the 5-year survival rate is 85% to 90%. Unfortunately 10% to 30% of the superficial tumours will progress to a muscle invasive tumour, which has a poorer prognosis. The greatest concern in patients with superficial TCC is therefore twofold: to lower the number of recurrences and to prevent progression.In an attempt to prevent or delay tumour recurrence or progression, adjuvant therapy after TUR has become common practice. The different chemotherapeutical modalities currently used and investigated for the treatment of TCC of the bladder are reviewed, starting with the first drug shown to be effective for treatment of superficial bladder cancer and chronologically leading to the latest treatment options.     

Risk of post-operative intravesical mitomycin C instillation following transurethral bladder tumor resection

Bladder cancer is the fifth most common cancer in the Western world and is on the rise. Most patients present with superficial disease and are treated by transurethral resection of bladder tumor. More than half of these patients experience recurrence with about 20% progressing to muscle invasive disease. Intravesical chemotherapy has been shown to decrease the risk of recurrence of bladder cancer. Mitomycin C has emerged as a major agent for an immediate post-resection intravesical instillation. This article reviews the literature on the mode of action, rationale for immediate adjuvant treatment with Mitomycin C and adverse effects associated with its use.     

术前热疗联合灌注化疗对肺癌细胞凋亡及相关基因的影响

目的 探讨术前热疗联合灌注化疗对非小细胞肺癌细胞凋亡及相关基因表达的影响. 方法 A组37例接受术前热疗联合灌注化疗,B组31例术前灌注化疗,C组15例直接手术治疗.检测手术前后癌细胞的凋亡指数(AI)、癌组织中PCNA、bcl-2和p53蛋白的表达和增殖指数(PI),比较3组上述指标治疗前后变化. 结果 A组术后癌细胞AI较治疗前增加,PI下降;bcl-2、p53蛋白阳性表达均较治疗前下调.B组癌细胞Al较治疗前增加;PI较治疗前下降;bcl-2、p53蛋白阳性表达均较治疗前下调.治疗后组间比较,A组的AI高于B组,PI低于B组; bcl-2、p53蛋白阳性表达A组较B组下降. 结论 术前热疗联合灌注化疗可使中晚期肺癌癌组织AI增加,P1下降,bcl-2、p53蛋白阳性表达下调.     

Neoadjuvant chemotherapy in muscle-invasive bladder cancer: Ready for prime time?

Through a Medline search from January 1, 1998 to February 29, 2012, the literature data supporting the standard use of neoadjuvant or adjuvant chemotherapy in the perioperative setting for muscle-invasive transitional cell carcinoma of the bladder were reviewed. Randomized phase III trials and meta-analyses have shown a significant benefit (level I evidence) in overall survival for neoadjuvant chemotherapy, with a 5% absolute benefit at 5 years, provided cisplatin-based combination regimens are used. Major methodological biases preclude any firm conclusion regarding the routine use of adjuvant therapy. The optimal chemotherapy regimen remains to be determined. Predictive biomarkers are urgently needed in order to determine which patients are more likely to benefit from neoadjuvant chemotherapy.     

Perioperative chemotherapy for upper tract urothelial cancer

Upper tract urothelial cancer (UTUC) is an aggressive disease associated with significant morbidity and mortality. Radical nephroureterectomy (RNU) with bladder cuff removal is considered the standard of care for most invasive UTUCs but distant relapses after surgery for locally advanced, high-grade disease are common. Although multimodality treatment with perioperative chemotherapy has been investigated thoroughly in recent years, adjuvant chemotherapy has primarily been analyzed in small retrospective uncontrolled studies and a clear benefit for this treatment modality is yet to be established. It is likely that the high incidence of renal insufficiency after surgery substantially limits the applicability of adjuvant chemotherapy with cisplatin-based regimens. Neoadjuvant cisplatin-based chemotherapy has several practical advantages over adjuvant therapy, including better patient tolerance in the preoperative setting when a patient has two kidneys rather than one and the obtainment of prognostic information from pathological downstaging. Although, some academic centers have adopted neoadjuvant chemotherapy as a de facto treatment standard for patients with high-grade locally advanced UTUC, this treatment approach has not been prospectively validated or adopted in general urologic practice. A multicenter trial of neoadjuvant chemotherapy for locally advanced high-grade UTUC could further define the role of neoadjuvant chemotherapy in treating UTUC.     

Bladder cancer.

Bladder cancer is the second most frequent tumour of the urogenital tract. Tobacco smoke has been shown to increase the risk of bladder cancer two- to fivefold as well as the exposure to metabolites of aniline dyes and other aromatic amines. Seventy-five per cent of bladder cancers are superficial at initial presentation, limited to the mucosa, submucosa, or lamina propria. Recurrence rates after initial treatment are 50-80%, with progression to muscle-invading tumour in 10-25%. In muscle-invading bladder cancers, there is a 50% risk of distant metastases. Surgery is the mainstay of standard treatment both in the form of transurethral endoscopic resection, mainly for superficial disease, and in the form of open ablative surgery with urinary diversion for muscle invasive disease. Endovesical administration of BCG has been employed after endoscopic resection as the most effective agent for both prophylaxis of disease recurrence and progression from superficial to invasive disease. The accepted treatment for muscle infiltrative disease is radical cystectomy. Response rates to combination chemotherapy regimens of up to 70% in patients with advanced metastatic disease have led to an investigation of its use for locally invasive disease in combination with conventional modalities of treatment.     

深部热疗联合化疗在晚期小细胞肺癌中的疗效观察

目的探讨深部热疗结合化疗在晚期小细胞肺癌中的临床效果。方法将80例晚期小细胞肺癌患者随机平均分成治疗组和对照组,每组各40例。2组患者均采用依托泊苷联合顺铂常规化疗治疗,治疗组患者在化疗同时给予肺部原发病灶深部热疗;比较6周期后两组患者的缓解率、无进展生存期、体能变化及不良反应。结果治疗组患者的缓解率为85.0%,对照组患者的缓解率为67.5%,治疗组缓解率显著高于对照组(P<0.05);治疗组的无进展生存期明显高于对照组(P<0.05);治疗组KPS评分较化疗前明显增加(P<0.05),对照组KPS评分较化疗前比较差异无统计学意义;2组患者的恶心、呕吐、及骨髓抑制程度明显低于对照组,但均无统计学意义(P>0.05)。结论晚期小细胞肺癌患者在化疗的同时联合深部热疗可显著提高患者的化疗疗效,延长患者生存时间,减轻患者化疗的不良反应,提高患者生存质量。     

Trends in endocrine therapy and chemotherapy for early breast cancer: a focus on the premenopausal patient

Purpose: The majority of breast cancers are diagnosed at an early stage, and treatment is focused on cure and prolonging disease-free survival. Local therapy (surgery and/or radiation treatment) is standard, along with systemic adjuvant therapy that may effectively prevent or delay relapse and death in early-stage disease. In premenopausal women, adjuvant therapeutic approaches include combination cytotoxic chemotherapy and endocrine therapy. Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) was the established chemotherapy regimen; however, newer regimens have more recently been introduced that may offer some benefit over CMF including anthracycline-containing regimens [e.g. cyclophosphamide, epirubicin and 5-fluorouracil (CEF)], and taxane-containing regimens. For women with oestrogen receptor (ER)-positive disease, a second option is endocrine therapy that aims to suppress mitogenic oestrogen signalling. Until recently, 5 years of tamoxifen was regarded as the standard adjuvant endocrine treatment in ER-positive disease. Ovarian ablation is also effective in premenopausal women, and can be achieved by surgery, radiotherapy, or via the use of a luteinising hormone-releasing hormone analogue such as goserelin. Combining tamoxifen and goserelin treatment provides more effective oestrogen blockade than either drug alone. However, as the third-generation aromatase inhibitors (AIs) have demonstrated improved efficacy over tamoxifen in postmenopausal women with early and advanced disease, combination treatment with goserelin plus an AI may provide optimal oestrogen blockade in premenopausal patients. Conclusions: This review assesses the relative merits of chemotherapeutic and endocrine approaches for the treatment of early breast cancer, and summarises relevant ongoing clinical trials, with an emphasis on the premenopausal setting.     

Treatment of small-cell lung cancer

Treatment of small cell lung cancer (SCLC) is based on the stage of disease. While combination of chemo- and radiotherapy preferably as concomitant chemoradiotherapy represents standard treatment in patients with locally advanced tumors (UICC stage I-III), patients with metastatic disease (stage?IV) should be treated with an established platinum based chemotherapy regimen. After chemotherapy and in case of an achieved tumor response treatment should be completed by an adjuvant radiation of the brain in patients with adequate performance status. In patients with a very early stage of disease without involvement of lymph node metastasis a surgical approach in combination with an adjuvant chemotherapy can be discussed. In patients with relapsed tumors second line therapies like the topoisomerase I inhibitor Topotecan have proven efficacy. Up to now neither molecular targeted therapies nor cytotoxic or immunological maintenance strategies have provided any benefit to patients with SCLC.     

Intravesical therapy of superficial bladder cancer

The aim of treatment of superficial bladder cancer with intravesical therapy is threefold: (1) Eradicate existing disease. (2) Prevention of recurrence. (3) Prevention of tumor progression. The prognostic factors allow differentiation in different risk groups and this is useful in planning treatment. Studies on pharmacokinetics have proved the efficacy of optimized drug delivery. Comparing resection with and without intravesical chemotherapy a short term approximately 15% decrease in tumor recurrence with chemotherapy can be obtained but no effect on progression was proven. No agent has proved more effective than the other. Single, early instillation of chemotherapy has proven effective but the role of maintenance therapy has been controversial. Immunotherapy in the form of Bacillus Calmette-Guerin generally have proven more efficacious than chemotherapy. The results in comparison to mitomycin C have not been as conclusive. Several new approaches are explored to improve the efficacy of this therapy.     

Advances in chemotherapy for colorectal cancer.

Gastroenterologists have a primary role in the management of colorectal cancer patients in that they frequently establish the diagnosis, direct or perform tumor staging evaluations, and initiate referrals for oncologic treatment. Several important advances have been made in the adjuvant treatment of colon and rectal cancers and in therapy of metastatic disease. These advances include the development of more effective combination chemotherapy regimens and molecularly targeted antibodies. These antibodies are directed against regulators of angiogenesis (vascular endothelial growth factor) and tumor cell growth (epidermal growth factor receptor) and have been shown to enhance the efficacy of cytotoxic chemotherapy. In the treatment of localized rectal cancer, the integration of chemotherapy and radiation with surgery has resulted in neoadjuvant approaches that achieve improved tumor control, sphincter preservation, and reduce treatment-related toxicities. This review presents an update of the current approach to colon and rectal cancer treatment, highlighting recent chemotherapeutic advances in the management of these highly prevalent malignancies.     

Peritoneal carcinomatosis of colorectal cancer: incidence,prognosis, and treatment modalities

Background and aims Intraperitoneal carcinomatosis accounts for 25–35% of recurrences of colorectal cancer. Studies demonstrate that peritoneal carcinomatosis is not necessarily a terminal condition with no options for treatment or cure.Results The combination of aggressive cytoreductive surgery and intra-abdominal hyperthermia chemotherapy improves long-term overall survival in selected patients but is a time-consuming procedure (approx. 12 h) and entails high mortality (5%) and morbidity (35%)). Most commonly used drugs are mitomycin C and platinum compounds, which have synergistic toxic effects on tumor cells when hyperthermia is applied.Conclusion Since combined treatment seems promising only in peritoneal carcinomatosis stages I and II, the precondition for a reasonable combined treatment is careful staging. The mode of chemotherapy, the kind of drugs used for chemoperfusion, the timing of surgery, and the role of additional systemic chemotherapy must be evaluated in randomized studies.     

Therapie des kleinzelligen Lungenkarzinoms

Treatment of small cell lung cancer (SCLC) is based on the stage of disease. While combination of chemo- and radiotherapy preferably as concomitant chemoradiotherapy represents standard treatment in patients with locally advanced tumors (UICC stage I?CIII), patients with metastatic disease (stage?IV) should be treated with an established platinum based chemotherapy regimen. After chemotherapy and in case of an achieved tumor response treatment should be completed by an adjuvant radiation of the brain in patients with adequate performance status. In patients with a very early stage of disease without involvement of lymph node metastasis a surgical approach in combination with an adjuvant chemotherapy can be discussed. In patients with relapsed tumors second line therapies like the topoisomerase I inhibitor Topotecan have proven efficacy. Up to now neither molecular targeted therapies nor cytotoxic or immunological maintenance strategies have provided any benefit to patients with SCLC.     

Place of cryotherapy, brachytherapy and photodynamic therapy in therapeutic bronchoscopy of lung cancers.

Cryotherapy, brachytherapy and photodynamic therapy (PDT) are three different methods proposed in the endoluminal treatment of lung cancers. The current article presents an overview of the specific indications and limits of each technique. These three methods were first proposed with palliative intent in inoperable patients with centrally located lung cancers. Now, the best indication is a curative intent in early stage lung cancers. Of the three, cryotherapy is the cheapest method. It induces cell necrosis in a 3-mm radius around the probe, and is suitable for treatment of superficial tumours. However, clinical trials are limited. In contrast, many clinical studies have confirmed the efficacy of PDT in treatment of superficial lung cancers. Brachytherapy can cure more aggressive tumours with deeper invasion into the bronchial wall. Unfortunately, no comparative studies have been published. Each of these methods induces a delayed tumour necrosis, and thus neither is indicated in the treatment of obstructive tumours with acute dyspnoea. In many situations, these methods should be complementary, particularly cryotherapy and brachytherapy or PDT and brachytherapy. The combination of these endoscopic methods with chemotherapy should be widely tested to promote the adjuvant role of the endoscopic methods in the treatment of lung cancers.     

Vaccines in non-small cell lung cancer: rationale, combination strategies and update on clinical trials

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer related mortality worldwide and despite some advances in therapy the overall prognosis remains disappointing. New therapeutic approaches like vaccination have been proposed and several clinical trials are ongoing. Many tumor antigens have been identified so far and specific tumor vaccines targeting these antigens have been developed. Even if the ideal setting for vaccine therapy might be the adjuvant one, vaccines seem to be potentially beneficial also in advanced disease and combination therapy could be a promising treatment option. In the advanced setting anti-MUC-1 vaccine (belagenpumatucel) and anti-TGF-β(2) vaccine (BPL-25) have entered in phase III trials as maintenance therapy after first line chemotherapy. In the adjuvant setting the most relevant and promising vaccines are directed against MAGE-A3 and PRAME, respectively. We will review the key points for effective active immunotherapies and combination therapies, giving an update on the most promising vaccines developed in NSCLC.     

TUPKR—Bt联合髂内动脉灌注化疗治疗多发性膀胱癌临床观察

目的探讨经尿道双极等离子体汽化电切术（TUPKR-Bt）联合髂内动脉灌注化疗治疗多发性膀胱癌的疗效。方法对25例多发性膀胱癌患者行TUPKR-Bt联合髂内动脉灌注化疗,观察手术情况及疗效。结果膀胱肿瘤切除率100％,手术时间20～60min,术中未输血;2a内复发6例,元明显并发症。结论TUPKR—Bt联合髂内动脉化疗治疗多发性膀胱癌,操作简单、损伤小、出血少、术后恢复快,适用于不能或不愿行膀胱全切术者。