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在就诊的原发性肝癌病人中 ,大多数已至晚期 ,如不积极、合理地进行治疗 ,预后很差 ,生存期仅 3～ 6个月 ,对这些病人治疗的研究具有很大的社会意义。何谓晚期肝癌 ?根据 1977年我国拟定的肝癌分期标准和 1999年全国肝癌会议对分期修改讨论稿 ,Ⅲ期 (Ⅲａ、Ⅲｂ)为晚期肝癌[1 ] ,临床缺少有效治疗方法。根据国内外文献和临床多年的实践经验 ,均认为对晚期肝癌特别那些尚无黄疸、腹水 ,肝功能尚好的Ⅲａ期病人应根据不同病情 ,恰当合理的选择和联合不同方法进行多模式综合治疗 ,可获得病情缓解 ,延长生存期 ,部分病例可能获得意外的良好疗效…     

Multimodal therapy in locally advanced breast carcinoma

Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease.     

Multimodality management of locally advanced rectal cancer

Despite the routine use of adjuvant chemoradiation for curatively resected stage II and III rectal cancer a significant percentage of patients ultimately fail locally and/or distally; this underscores the need for continued improvement in the efficacy of combined-modality therapy and quality of rectal cancer resection. The recognition of the significance of lateral or circumferential margins of resection has paralleled the widespread use of total mesorectal excision. In addition to facilitating negative margins of resection and local control, sharp mesorectal techniques also facilitate identification and preservation of pelvic autonomic nerves thereby greatly reducing the incidence of urinary and sexual dysfunction following radical resection. Lastly, restorative options can result in excellent bowel function in carefully selected patients undergoing a "very low" anterior resection. Efforts are currently directed at identifying the subset of locally advanced rectal cancer patients who may be adequately treated with a resection alone thereby avoiding the added morbidity of adjuvant radiation and chemotherapy.     

Surgical treatment of locally advanced differentiated thyroid carcinoma

Patients with differentiated thyroid carcinoma (DTC), especially with papillary carcinoma, occasionally have direct tumor extension with invasion of surrounding tissues The presence of extrathyroidal invasion is one of the most important risk factors for mortality from DTC. However, leaving microscopic DTC on the surrounding structures usually does not lead to decreased survival or increased locoregional recurrence. Although endoscopic examinations, computed tomography, magnetic resonance imaging, and clinical presentations including hoarseness, dyspnea, and dysphagia are useful for the diagnosis of extrathyroidal extension, it is not easy to discriminate cancer invasion of adjacent structures from cancer adhesion preoperatively. The optimal surgical approach in patients with locally advanced DTC is controversial. Some experts support a conservative shave excision. They claim that these high-risk patients frequently have distant metastases and tumor dedifferentiation, and that survival advantage from extended surgery at the expense of significant morbidity is unclear. Others advocate an aggressive en bloc resection of the tumor and involved vital structures when technically feasible, because elimination of the risks of suffocation or major vessel hemorrhage is beneficial to patients. This paper discusses the management of patients with locally advanced DTC involving the recurrent laryngeal nerve, laryngotrachea, esophagus, major vessels, and mediastinum.     

Surgical adjuvant treatment of locally advanced breast cancer.

The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer.     

胰腺癌的综合治疗

胰腺癌是消化系统常见的恶性肿瘤，目前多学科、多中心联合的综合治疗已经在许多方面取得了一定的进展，其综合治疗包括外科治疗、化疗、放疗、物理及生物治疗等。胰腺癌的治疗以手术为主，实行合理的手术切除可以改善病人的长期生存率及生活质量。放射治疗可分为与手术联合的辅助性放疗及姑息性放疗，术前放化疗，可以提高手术切除率，并减少肿瘤扩散，术中放疗可以缓解疼痛，提高生存率，术后辅助放化疗的作用仍有争议。化疗分为全身和区域性化疗，区域性化疗为选择性动脉给药，理论上有诸多优势，但仍需数据支持。物理治疗和生物治疗在胰腺癌的治疗中也已经得到广泛的重视。但只有建立以手术切除为主，联合放疗、化疗、物理及生物治疗的综合治疗体系，才有可能提高病人的长期生存率，改善病人的生活质量。     

Management of locally advanced breast cancer

The management of locally advanced breast cancer with single modality therapy has been associated with a high rate of systemic failure. A multimodality treatment strategy that includes induction cytotoxic chemotherapy, surgery, radiation therapy, and, possibly, hormonal ablation therapy is the current preferred management approach. As our knowledge and understanding of the mechanisms involved in mitogenic signal transduction improve, it is likely that less toxic, more effications agents will emerge.

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Resumen La denominación taxonómica cáncer mamario localmente avanzado (CMLA) comprende un significativo número de pacientes con pronósticos variables. A pesar de la incrementada preocupación por el cáncer mamario por parte tanto del público como de los médicos, 10% a 15% de las mujeres con cáncer del seno presentan CMLA en el momento del diagnóstico. En el año 1991, en los Estado Unidos se diagnosticaron 175.900 mujeres con cáncer mamario, de las cuales más de 17.000 presentaban CMLA. Esto significa que la entidad es más frecuente que la Enfermedad de Hodgkin, el carcinoma diferenciado de la glándula tiroides y el carcinoma invasivo del cervix. La diversidad biológica de esta enfermedad impide definir un tratamiento uniforme para el CMLA: existen 13 combinaciones posibles con base en el sistema TNM actual de estadificación para el cáncer mamario Estado III, que van desde tumores mínimos con invasión axilar voluminosa hasta grandes tumores con invasión axilar microscópica. La interpretación retrospectiva de información pertinente al CMLA es difícil, por cuanto el sistema de Estadificación de la Comisión Conjunta (American Joint Committee & Taging System) ha cambiado por lo menos cuatro veces desde 1962, y por lo menos otros dos sistemas de clasificación han sido utilizados: el sistema de Manchester y el sistema de clasificación de la Universidad de Columbia. Tales factores se combinan para hacer muy dificil la evaluación de los resultados del tratamiento o la formulación de un enfoque terapéutico unificado en mujeres con CMLA. El tratamiento local sólo, bien sea por ablación quirúrgica o por radioterapia, se asocia con una tasa elevada de falla sistémica, lo cual sugiere que en la mayoría de los casos exista enfermedad micrometastásica. Por lo tanto, es necesario emplear una estrategia multimodal que acentúe tanto el control local como una agresiva terapia sistémica.

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Résumé La dénomination carcinome du sein localement avancé (CSLA) regroupe un nombre important de patientes dont le pronostic est variable. En dépit d'un public général et médical de plus en plus averti, 10 à 15% des femmes américaines avaient, en 1991, un CSLA au moment du premier diagnostic. Ceci correspond à 175900 femmes dont 17000 ayant un CSLA. Avec une telle prévalence, la fréquence du CSLA est plus élevée que celle de la maladie de Hodgkin, le cancer différencié de la thyroïde ou le cancer invasif du col utérin. Pouvoir proposer un plan thérapeutique uniforme des CSLA n'est pas facile en raison de la diversité clinique de la maladie (il y a 13 combinaisons possibles et la classification TMN actuelle des stades III comporte des tumeurs minimes avec envahissement axillaire important ainsi que de volumineuses tumeurs avec envahissement axillaire minime). L'analyse rétrospective des résultats est difficile car l'American Joint Committee Staging System a changé au moins quatre fois depuis 1962 et qu'il existe au moins deux autres systèmes de classification de gravité (Manchester et la Columbia Clinical Classification System). Ceci explique pourquoi il est difficile de formuler une approche thérapeutique standardisé pour les femmes ayant un CSLA. Le traitement local, soit par la chirurgie seule, soit par la radiothérapie est associé à un taux de récidive à distance élevée, suggérant que des micrométastases sont présentes dans la majorité des cas. Une stratégie multimodale, comportant une exérèse locale et un traitement systémique agressif est obligatoire.

     

Sequence of treatment in locally advanced and metastatic renal cell carcinoma

The spectrum of drugs that have shown activity in advanced or metastatic renal cell carcinoma (RCC) has led to a debate on the optimal sequence of treatments. There is agreement on recommending targeted agents as the standard of care in this disease. Uncertainty, however, remains on the best first-line drug choice. Physicians and patients may select sunitinib, bevacizumab in combination with interferon-alpha (IFN-α), pazopanib, or—in poor risk patients—temsirolimus. There are also a variety of therapies with proven efficacy on hand in the second-line setting: sorafenib, pazopanib, axitinib, and everolimus. While most randomized RCC trials assessed progression free survival (PFS) as primary endpoint, some agents were shown to improve median overall survival (OS), and given in sequence they have extended the life expectancy of RCC patients from 13 months in the cytokine era to over 30 months. Despite the progress made, there are sobering aspects to the oncologic success story in RCC, as the new treatments do not obtain an objective response or disease stabilization (SD) in all patients. There are also as yet no predictors to select patients who might benefit and those who are primary resistant to specific drugs, and ultimately almost all patients will experience disease progression. Bearing inevitable treatment failure in mind, availability of further drugs and switching therapy while the patient is in a condition to continue pharmacotherapy is essential. Of note, depending on the setting, only 33-59% of patients receive second-line treatment. In this review we present data on first-, second-, and third-line treatment in RCC, and discuss the difficulties in their interpretation in the context of treatment sequence. We summarize biological aspects and discuss mechanisms of resistance to anti-angiogenic therapy and their implications for treatment selection.     

Primary chemo-radiotherapy in the treatment of locally advanced and inflammatory breast cancer

BackgroundThe best management of large, diffuse or inflammatory breast cancers is uncertain and the place of radiotherapy and/or surgery is not clearly defined.MethodsA cohort of 123 patients with non-metastatic locally advanced or inflammatory breast cancer 3 cm or more in diameter or T4, was treated between 1989 and 2006. All patients received primary chemotherapy followed by radiotherapy, 40 Gy in 15 fractions with 10 Gy boost. Patients with ER positive tumours received Tamoxifen. Assessment was carried out 8 weeks post-treatment and surgery was reserved for residual or recurrent disease.ResultsFor each stage there were T2/3: 63, T4b: 31 and T4d: 29 patients. 80 had complete clinical response (65%) but 18 patients were never free of inoperable local disease. 25 patients had residual operable disease at assessment and 12 patients who initially had a complete response developed operable local recurrence (LR). 37 Patients (30%) had surgery at a mean of 15 months post diagnosis. At 5 years, overall survival (OS) of the two surgical groups was not significantly different from those 68 patients who had complete remission without surgery, p = 0.218, HR 1.46 (0.80–2.55). Surgery as an independent variable to predict survival was not significant on a Cox proportional hazards model (p = 0.97). LR in the surgical groups was 13.5% vs 17.5% in the non-surgical patients. The median OS was 64.5 months and disease-free survival (DFS) was 52.5 months. 5-Year OS was 54% and DFS survival 43%.ConclusionIn patients with a complete or partial response to chemo-radiotherapy for locally advanced or inflammatory breast cancer, reserving surgery for those with residual or recurrent local disease did not appear to compromise survival. This finding would support examination of this treatment strategy by a randomised controlled trial.     

Omental transposition in the treatment of locally advanced and recurrent breast cancer

An analysis was carried out of 43 patients treated by omental transposition for locoregional problems associated with breast cancer. Indications for surgery included advanced primary tumour (five), locally recurrent tumour (32), radiation induced sarcoma (two), and radionecrosis (four). Tumours were typically extensive (mean diameter 7.2 cm) and skin ulceration affected 30 patients. Other treatment modalities had been exhausted. Surgical excision followed by reconstruction using transposed omentum resulted in worthwhile local control and symptom relief in 31 patients (median duration 22 months). Chest wall disease rapidly recurred peripheral to the omental graft in 12 patients. On multiple regression analysis, duration of local control was significantly related to tumour diameter, ulceration, and earlier radioresistance (hazard ratios 15.8, 3.8 and 14.8 respectively). Survival (median 21, range from 1.5 to 122 months) correlated with tumour size, previous chemotherapy, and early re-recurrence (hazard ratios 7.2, 3.0 and 4.3). Omental transfer is a reliable method of restoring epithelial cover after radical surgery and is particularly useful after previous irradiation injury. In advanced and recurrent breast cancer, an aggressive surgical approach significantly improved the quality of life of most patients, but careful case selection is required to avoid inappropriate surgery for irremediable tumours.     

盆腔脏器联合切除在局部进展期直肠癌治疗中的意义

约6%~10%的原发直肠癌及50%的复发直肠癌局部病变广泛,肿瘤长时间浸润盆内脏器或组织而不发生远处转移[1],这些肿瘤被称为局部进展期直肠癌(locally ad-vanced rectal carcinoma,LARC),传统手术难以根治,放疗仅能短暂缓解疼痛。LARC未经手术切除治疗者平均生存时间为7~8个月,不     

Treatment of locally recurrent breast carcinoma

Treatment of locally recurrent breast carcinoma remains a significant problem. The records of 106 patients with local chest wall recurrence were reviewed. Fifty-five percent eventually developed metastatic disease, while 45% remained free of systemic disease. Size of primary tumor (greater than 2 cm), number of recurrences (multiple), and disease-free interval from primary surgery (less than 2 years) were all highly significant for the development of metastatic disease. Negative estrogen receptors also predicted bad prognosis. Both irradiation and surgery used alone had high local failure rates of 83% and 62%, respectively, but combination radiation-surgery treatment failed only in 25%. Combination radiation-surgery treatment should be considered in patients with local recurrence, but further prospective trials with more patients will be needed to prove its effectiveness. Patients with unfavorable prognostic factors should be considered for adjuvant chemotherapy.     

Radiofrequency thermoablation in locally advanced breast cancer

The authors report their experience of 8 cases of breast cancer in six patients, treated by radiofrequency thermoablation. Two patients had bilateral breast cancer infiltrating the skin. All patients, but one, were alive at two years follow-up. The age range was 54-75 years old (median, 71 years old). We observed complete regression in one patient, regression with residual scar in two patients and partial regression in the remaining three patients. The authors believe that radiofrequency, alone or associated with other treatments, is an easy and useful alternative for the management of breast cancer, in selected patient who cannot undergo surgery or refuse surgical treatment and other treatments.     

Multimodal therapy for locally advanced breast cancer

Thirty-one women with stage III breast cancer were prospectively treated with two cycles of cyclophosphamide (Cytoxan), doxorubicin hydrochloride (Adriamycin), fluorouracil, and tamoxifen citrate followed by a simple mastectomy with level I axillary dissection. Postoperatively, four additional cycles of the combination chemotherapy alternating with three cycles of 1500 rad (15 Gy) to the chest wall and lymphatics were given. Seventy-seven percent of patients had a greater than 50% reduction in tumor size after the initial chemotherapy. No tumor size progressed during therapy, and a single patient remained inoperable. Pathologic findings revealed nine patients with only microscopic residual tumor. Nuclear vacuolization was present in 42.8% of tumor cells after chemotherapy vs 14.2% of cells before chemotherapy. The mean follow-up for the groups is 24.3 months. To date, nine patients have had recurrence with only one isolated local recurrence. This therapy is effective in reducing primary tumor size and allows a limited mastectomy to be done with minimal morbidity.