Adjuvant treatments for resectable pancreatic cancer

Pancreatic cancer remains one of the most challenging malignancies to treat successfully. The majority of patients present with unresectable advanced-stage cancer, and only 20% of patients can undergo resection. Even if surgical resection is performed, the recurrence rate is high and the survival rate after surgery is poor. Therefore, effective adjuvant therapy is needed to improve the prognosis of patients with pancreatic cancer. Until now, no universally accepted standard adjuvant therapy for this disease has been available: chemoradiotherapy followed by chemotherapy is considered the optimal therapy in the United States, while chemotherapy alone is the current standard in Europe. However, recent randomized controlled trials (RTOG [Radiation Therapy Oncology Group] 9704; CONKO [Charité Onkologie]-001; and a Japanese study) have suggested a benefit of adjuvant chemotherapy with gemcitabine for patients with resectable pancreatic cancer. This article will review the clinical trials of adjuvant therapy for this disease, including the results of recent trials.     

Adjuvant Therapy for Adenocarcinoma of the Pancreas: Analysis of Reported Trials and Recommendations for Future Progress

The delivery of postoperative combined modality adjuvant therapy for completely resected pancreatic cancer was initially shown to be beneficial on the basis of a prospective, randomized trial published in 1985. Since then, oncologists have debated whether chemotherapy, chemoradiation, or both is optimal adjuvant therapy after pancreatectomy for ductal adenocarcinoma of the pancreas; no global consensus has emerged. Unfortunately, despite the completion of a number of subsequent randomized trials of adjuvant therapy since 1985, no further improvements in overall survival have materialized. This lack of progress is not simply the result of ineffective systemic therapies, but in part the result of poor trial design and calls for a more disciplined approach to the selection of patients for surgery, pathologic assessment of surgical resection margins, and postoperative (pretreatment) imaging. This is the only way to ensure that patients who receive adjuvant therapy are actually receiving therapy for radiographically occult possible microscopic disease, rather than therapy for incompletely resected locally advanced disease or early postoperative metastases. A critical analysis of completed adjuvant trials will be provided and a framework for the conduct of future trials of adjuvant therapy proposed.     

Pancreatic carcinoma. Optimizing therapy by adjuvant and neoadjuvant therapy?]

Increasing resection rates for pancreatic tumors and decreasing postoperative mortality rates in specialised centres let arise the question of an additional benefit of adjuvant therapy. Despite of extended and radical surgery the recurrence rates after resection of pancreatic cancer remain high. Several studies have indicated some chemo- and radiosensitivity of these tumors. Whether a (combination-)chemotherapy alone or a combined radiochemotherapy should be recommended can actually not be answered yet. However, adjuvant radiotherapy alone seems to be inferior to combined radiochemotherapy. Intraoperative radiotherapy as well as preoperative radiotherapy are not superior to postoperative percutaneous radiotherapy regarding recurrence rate and survival. Preoperative radiotherapy, preferably in combination with chemotherapy, should be considered in patients with non resectable or borderline resectable pancreatic tumors with the aim of downstaging and secondary resection. The preliminary results of regional adjuvant chemotherapy are impressing, but need to be confirmed in further, randomised studies. Overall, the availability of a good or even optimal adjuvant therapy for pancreatic cancer still seems to be far away. Therefore, all surgeons need to be encouraged to include their patients with resected pancreatic carcinoma in a current study protocol of adjuvant treatment, since only tenacious and multicentric research can lead to progress in this severe disease.     

Chemotherapy of colorectal cancer

Although considerable research effort has been expanded to improve the drug treatment of colorectal cancer, progress has been slow. 5-fluorouracil (5-FU) is still the agent of choice and no other drug or combination of drugs has been found superior. When combined with radiation therapy 5-FU is superior to irradiation alone in the treatment of localized carcinoma of the rectum. When used as an adjuvant in the management of patients with a poor prognosis after definitive surgical resection, 5-FU has not improved survival or delayed the time to recurrence. Further controlled trials are modalities of therapy to improve these results.     

Surgical treatment of carcinoma of the pancreas

Invasive ductal carcinoma of the pancreas (pancreatic cancer) is mainly treated by operative resection, radio-chemotherapy, or chemotherapy. The survival rate of the patients with each treatment is not good when compared with that in other cancers. Meanwhile, it is still true that surgical resection remains the only method offering pancreatic cancer patients long-term survival or cure. The indications for surgical resection should be considered based on whether margin-free resection can be achieved in individual patients. In addition, the volume of pancreatic cancer patients treated at the institution and the surgeon's personal experience may greatly affect the decision. A recent randomized clinical trial from Japan revealed that surgical resection has a survival advantage over chemo-radiation therapy for locally advanced pancreatic cancer, which is defined as stage IVa in the fourth Japanese edition of the Classification of Pancreatic Carcinoma. Moreover, guidelines for clinical practice for pancreatic cancer by the Japan Pancreas Society have been issued very recently. In addition, the surgical indications should be reevaluated in combination with the adjuvant or neoadjuvant chemotherapy in future.     

临界可切除胰腺癌的诊疗策略

胰腺癌早期诊断困难,80%的患者就诊时已发生局部进展或远处转移。目前,手术切除仍是胰腺癌患者获得长期生存的唯一方法。近年来,胰腺癌综合治疗水平较前有所提高。针对临界可切除胰腺癌进行新辅助治疗,可以达到降期,甄别人群,筛选潜在获益人群进行手术的目的。合理选择有效化疗方案,恰当选择手术时机,能进一步提高胰腺癌的切除率,从而延长该类高危人群的生存期。     

可切除胰头癌的治疗进展

胰腺癌是消化系统中恶性程度最高的肿瘤,远期预后极差.胰腺癌中胰头癌所占比例最高,所以胰头癌的治疗是胰腺癌治疗中的重点.根治性胰十二指肠切除术是胰头癌患者得以治愈的希望,同时也是患者长期生存的最重要的治疗方式.选择恰当的手术方式及技巧可以提高肿瘤根治性切除的几率,降低术后并发症;再结合适时、适当的辅助治疗,可能会改善可切除胰头癌患者术后生存质量并延长生存期.     

Optimal timing of radical cystectomy for patients with T1 bladder cancer

The optimal treatment of lamina propria invasive bladder cancers remains controversial. Assigning strict treatment guidelines is hampered by the heterogeneous clinical behavior of lamina propria invasive bladder cancers. Although many T1 lesions respond very well to transurethral resection and adjuvant intravesical therapy, others demonstrate a high rate of recurrence and progression. While bladder preservation is desired by most patients, experience has documented that survival is compromised in a substantial percentage of patients if T1 disease is allowed to progress. Radical cystectomy for T1 disease is associated with an excellent survival; however, the optimal timing of radical cystectomy remains one of the more difficult clinical dilemmas in the management of patients with bladder cancer. This article reviews the various features associated with an increased risk of disease progression to provide a framework for optimizing the timing of radical cystectomy.     

胰腺癌外科治疗的热点与争论

Pancreatic cancer is a common disease with a poor prognosis. Despite recent advance in the field of diagnos-tic technique, surgical resection and adjuvant therapy for pan-creatic cancer, the overall 5-year survival rate is still less than 5%. This is due to its aggressive growth behavior, early local invasion and metastasis, and resistance to chemotherapy and radiation therapy. Surgical treatment is still regard as the only chance for curing pancreatic cancer. Many new strategies in the surgical treatment of pancreatic cancer, including extended lymphadeneetomy, vascular resection, the use of laparoscopy, surgery for metastastic or recurrent disease, and neoadjuvant therapy, are currently under debate. In this review, we discuss the current status of surgical treatment for pancreatic cancer, and highlight the controversies and focus.     

Is Reporting of Recurrence Data Important in Pancreatic Cancer?

Background: Therapeutic approaches to patients with pancreatic cancer have undergone a paradigm shift in recent years. However, little is known about the outcome of patients with recurrent pancreatic cancer who undergo treatment. The purpose of this study was to identify patients with recurrent pancreatic cancer and to determine whether treatment after recurrence had any effect on outcome.Methods: A review of all patients undergoing surgical resection with curative intent revealed 70 patients with documented recurrence and complete medical records. Patients were grouped into three categories: group 1 included those who received treatment after recurrence (n = 45), group 2 included those who were not offered treatment (n = 9), and group 3 included those with poor performance status who received no treatment (n = 16).Results: The median overall survival for the three groups was 26, 18, and 14.5 months for groups 1, 2, and 3, respectively (P < .00001). The median survival after recurrence was 10 months, 6 months, and 1 month, respectively, for the three groups (P < .0001).Conclusions: This is the first series we are aware of that compares the outcomes of patients who received treatment after recurrence of pancreatic cancer with the outcomes of those who received no treatment. In this series, it seems that patients who were well enough to tolerate additional therapy had a longer survival than those who received supportive care only. This may be important in the analysis of adjuvant therapy trials of pancreatic cancer with survival as an end point.     

T3N0 rectal cancer: Results following sharp mesorectal excision and no adjuvant therapy

Adjuvant chemoradiation therapy following resection of T3N0 rectal cancer is recommended in order to reduce the incidence of local recurrence and improve survival. However, recent experience with rectal cancer resection utilizing sharp dissection and total mesorectal excision has resulted in a reduction in local recurrence rates to as low as 5% without adjuvant treatment. The purpose of this study was to determine if rectal cancer resection utilizing sharp mesorectal excision alone is adequate treatment for local control of T3N0 rectal cancer. Between July 1986 and December 1993, 95 patients with T3N0M0 rectal cancer underwent resection with sharp mesorectal excision and did not receive any adjuvant therapy. Various prognostic factors were analyzed for their association with local recurrence and survival. Seventy-nine patients had a low anterior resection, 10 of whom had a coloanal anastomosis, and 16 had an abdominoperineal resection. The median follow-up was 53.3 months. Six patients had local recurrence, 12 had distant recurrence, and three had local and distant recurrences. The overall local recurrence rate was 9% crude and 12% 5-year actuarial. The overall crude recurrence rate was 22%. The 5-year disease-specific survival rate was 86.6% with an overall survival of 75%. Postoperative complications occurred in 18 patients (19%). Five patients (6%) had a documented anastomotic leak. Perioperative mortality was 3%. No technical factors, including type of resection (low anterior vs. abdominoperineal), location of tumor, or extent of resection margin, were significant for determining local recurrence. The only histopathologic marker significant for determining local recurrence was lymphatic invasion (P <0.04). Sharp mesorectal excision with low anterior resection or abdominoperineal resection for T3N0M0 rectal cancer results in a local recurrence rate of less than 10% without the use of adjuvant therapy. Therefore, in select patients with T3N0M0 rectal cancer, the standard use of adjuvant therapy for local control may not be justified. Presented at the Thirty-Ninth Annual Meeting of The Society of Surgery for the Alimentary Tract, New Orleans, La., May 17–20, 1998.     

Established data and practical recommendations concerning pre- and postoperative chemotherapy of rectal cancer

Adjuvant chemotherapy appears to be active in stage II-III rectal cancers; the NSAPB R01 trial demonstrated a survival advantage for patients receiving chemotherapy using the MOF protocol and 3 meta-analyses are in favor of the efficacy of adjuvant chemotherapy in rectal cancer. Three randomized trials have also demonstrated that combinations of radiation and chemotherapy are superior to surgery alone or adjuvant radiotherapy and demonstrated the major role of systemic chemotherapy combined with radiotherapy. However this efficacy of adjuvant chemotherapy alone or combined with radiation therapy is still debated and specific trials must be conducted to test the value of chemotherapy using more active regimens than those previously tested and taking into account the quality of surgery and radiotherapy; such trials are in progress, especially the trial conducted by the EORTC and the FFCD. The efficacy of neoadjuvant chemotherapy has never been clearly demonstrated, although a combination of radiotherapy and chemotherapy as first-line treatment for locally advanced rectal cancer and in the case of synchronous metastasis seems to facilitate surgical resection. It is a reasonable and tolerable approach with manageable toxicity which gives substantial results in 2/3 of patients. This strategy also allows better selection of patients likely to benefit from surgical resection of their primary tumor and in some cases of their synchronous metastases. However, the efficacy of perioperative treatments should not decrease the quality of the surgical resection and especially mesorectal excision as well as the need for high quality pathological examination which must be very thorough with analysis of a sufficient number of lymph nodes. The efficacy of combined treatment in advanced rectal cancers is a major argument in favor of the multidisciplinary coordination required for optimal treatment of patients with rectal cancer.     

胰腺癌外科治疗的进展

作为2013年西方国家第四大癌症死亡原因,胰腺癌在新发癌症病例中已上升至女性第9位和男性第10位.由于早期检出率低,胰腺癌患者确诊时仅20%可手术,30%～40%为局部晚期,50%已全身转移,总体5年生存率仅6%.为提高早期检出率,内镜超声引导下穿刺活检是获得组织诊断的最佳方式,但准确率不高,故国际诊疗指南建议如有以下几点即可考虑外科手术：①囊性肿物直径〉2～3cm;②MRI和内镜超声中检出可疑结节;③导管内乳头状黏液瘤（IPMN）和黏液性囊腺瘤等癌前病变.1995年至2004年美国国家癌症数据库研究显示,手术患者的5年生存率为24.6%,而非手术患者仅为2.9%.因此,手术切除是患者获得长期生存和潜在治愈的唯一机会.外科手术技术和围手术期管理进步使胰腺手术更加安全,特别是围手术期疗效的进展,外科医生可以实施更加复杂的手术切除.因此,可切除标准亦有所放宽：①血管切除：过去视为不可切除,如今只要适合重建,肿瘤侵犯肝动脉、门静脉和肠系膜上静脉均可行边界性切除,但若肿瘤完全包绕腹腔干或者肠系膜上动脉则视为不可切除;②多脏器切除：对于侵犯了邻近器官（例如结肠系膜、结肠、胃）的局部浸润肿瘤均可行多脏器切除术;③扩大的淋巴结清扫术：扩大的淋巴清扫术并不能提高生存率,反而增加并发症率,因此,不推荐常规施行胰腺癌扩大的淋巴结清扫术;④腹腔镜胰腺切除术在胰腺癌中的应用：腹腔镜胰体尾切除术是可行且安全的,但目前仍缺乏腹腔镜胰头部切除术的肿瘤学长期效果的数据.研究报道,胰腺术后并发症发生率在小规模医院为16.3%,大规模医疗中心为3.8%,但病死率却控制在5%以下.最主要的并发症是术后胰瘘（POPF）,在此基础上,POPF增加了其他并发症的发生率,如腹腔脓肿、胰腺切除术后出血（PPH）和胃排空延迟（DGE）.对此,胰腺手术国际研究小组（ISGPS）认为减少POPF发病率的外科策略包括选择最安全的胰肠吻合或胰腺残端闭合技术、胰肠吻合的支架和通过生长激素抑制剂来减少胰腺外分泌,具体如下：①胰腺吻合：主要是胰空肠吻合和胰胃吻合,目前两种方式仍然没有结论 性的数据显示有差异,大多数大规模的胰腺外科中心采用胰空肠吻合术,但对于规模较小的机构而言,技术不太复杂的胰胃吻合术可能是更好的选择.②远端胰腺切除术的残端处理：为减少POPF的发生,已经探讨了若干项治疗策略,包括薄壁组织横断、胰腺残端闭合、胰腺残端额外覆盖和胰肠吻合的不同技术,但仍然是一个尚未解决的难题.③胰腺吻合时支架管的应用：不支持常规放置支架.④生长激素抑制剂：理论上会降低POPF的风险,但有研究报道生长抑素类似物尚不能有效治疗POPF.此外,术前胆汁引流显著增加了术后并发症率,而在病死率、住院时间和生存效果方面没有效果.故不推荐常规地施行术前胆道支架植入术,但以下患者除外：与凝血功能障碍有关的高胆红素血症患者,需要行新辅助治疗或姑息性化疗的局部浸润性肿瘤或者出现转移的患者.对于不可行手术切除的患者,有一种可以选择的方法 是施行新辅助治疗并尝试在肿瘤降期后行手术切除.原则上讲,放化疗可以更加有效地使局部降期,研究表明,吉西他滨（Gemcitabine）是辅助治疗的金标准,可增加术后生存率,但单独应用化疗还是放化疗联合应用仍存在争议.然而,由于大多数患者在手术切除后两年内发生了全身性的疾病进展,胰腺癌患者的长期疗效仍然不理想,故即便是可切除的胰腺癌也要视为一种全身性疾病.因此,将来手术技术发展可能不会给长期疗效带来可观的效果.为了提高长期效果,我们迫切地需要新的和更加有效的系统性治疗.     

肯定还是否定:胰腺癌新辅助治疗

目前胰腺癌的诊断与治疗策略正在由"surgery first"过渡至多学科团队模式。越来越多的证据表明:对于交界可切除及具有高复发风险因素的可切除胰腺癌,新辅助治疗有助于提高R0切除率,降低肿瘤复发率并改善患者预后。笔者述评目前胰腺癌新辅助治疗存在的争议并展望其发展方向,以提高临床外科医师对该热点问题的认知水平。     

胰腺癌综合治疗的现状

胰腺癌是一种难治性消化系统恶性肿瘤,具有病程短、进展快、病死率高等特点.由于胰腺解剖位置特殊,且缺乏特异性症状及检查手段,导致胰腺癌早期诊断困难.胰腺癌生物学行为特殊,早期易发生胰内、外的转移和侵犯.手术切除率<15%,病程不到1年.即使手术切除肿瘤,胰腺癌局部复发率和远处转移率仍相当高,患者5年生存率<5%,预后极差<'[1-2]>.同时,胰腺癌的发病率呈明显上升趋势,近20年增加了1～5倍.我国胰腺癌的发病率已由第22位(20世纪60年代)上升到第5位(20世纪90年代),相应的病死率由第15位上升至第6位<'[3-4]>.临床流行病学调查进一步显示,上海市胰腺癌发病率正以每年2%的速度增加,且病死率和发病率非常接近<'[5]>.如何进行合理的胰腺癌综合治疗已成为当务之急.纵观胰腺癌综合治疗的现状,主要包括以下7个方面.     

The role of total mesorectal excision in the management of rectal cancer

During the past decade, it has been clearly demonstrated that adjuvant treatment has the potential of improving not only prognosis in terms of local recurrence, but also in terms of overall survival. However, one of the largest improvements in the outcome of rectal cancer has been the introduction of total mesorectal excision. TME, with its large decline in local recurrence rate, has become the new standard of operative management for rectal cancers, replacing conventional resection technique [68]. In addition, current clinical trials examining the role of adjuvant therapy in patients who are undergoing standardized operations are now setting the standard of surgical care in several countries.     

胰腺癌外科治疗单中心10年临床经验分析

目的：探讨胰腺癌外科治疗的疗效。方法：回顾性分析我院普通外科2000--2010年经病理学检查或手术确诊的130例胰腺癌患者的临床资料。结果：130例胰腺癌患者中,首发症状前3位依次为腹痛、黄疸和消瘦,平均就诊时间91．99d。根治性切除27例（20．77％）,姑息性短路手术98例（75．38％）。I～II期患者手术切除率为85．19％,III～IV期为3．88％。根治性手术患者术后中位生存时间为20月,而捷径手术患者的术后中位生存时间为5月。结论：手术是目前治疗胰腺癌的唯一有效手段,I～II期患者手术切除率高,但预后并不令人满意。应加强胰腺癌的综合治疗,特别是对失去手术切除机会的中晚期患者的综合治疗。     

胰腺癌放射性核素内照射治疗现状及进展

胰腺癌是恶性程度高、进展迅速、预后极差的消化系统肿瘤,早期诊断困难,多数患者发现时已属晚期,失去手术治疗的机会,只能采取放化疗等辅助治疗手段来缓解症状及控制疾病。近年来随着放射性核素内照射治疗的不断发展,治疗策略的不断更新,其在胰腺癌的治疗中的作用越来越受到重视,笔者就其在胰腺癌治疗中的进展进行综述。