TRIANGLE operation,combined with adequate adjuvant chemotherapy,can improve the prognosis of pancreatic head cancer:A retrospective study

BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein,celiac axis-common hepatic artery,and superior mesenteric artery to improve patient prognosis.Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma(PDAC),data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy(PD).AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC.METHODS This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023,with or without the TRIANGLE operation.Patients were divided into the PD_(TRIANGLE)and PD_(non-TRIANGLE)groups.Surgical and survival outcomes were compared between the two groups.Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy≥6 months.RESULTS The PD_(TRIANGLE)and PD_(non-TRIANGLE) groups included 52 and 55 patients,respectively.There were no significant differences in the baseline characteristics or perioperative indexes between the two groups.Furthermore,the recurrence rate was lower in the PD_(TRIANGLE) group than in the PD_(non-TRIANGLE) group(48.1%vs 81.8%,P<0.001),and the local recurrence rate of PDAC decreased from 37.8%to 16.0%.Multivariate Cox regression analysis revealed that PD_(TRIANGLE)(HR=0.424;95%CI:0.256-0.702;P=0.001),adequate adjuvant chemotherapy≥6 months(HR=0.370;95%CI:0.222-0.618;P<0.001)and margin status(HR=2.255;95%CI:1.252-4.064;P=0.007)were found to be independent factors for the recurrence rate.CONCLUSION The TRIANGLE operation is safe for PDAC patients undergoing PD.Moreover,it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

Background： We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma（PAC）.Methods： A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013.Results： Of 563 patients, 472 received adjuvant chemotherapy（CT） alone, chemoradiotherapy（CRT） alone, and chemoradiotherapy plus chemotherapy（CRT-CT） were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival（RFS） and overall survival（OS） were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant differencebetween groups when patients with node-negative disease or patients with or without positive surgical margins were considered.Conclusions： Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

Comparison of efficacy between adjuvant chemotherapy and chemoradiation therapy for pancreatic cancer: AJCC stage-based approach

BACKGROUND The adjuvant treatment for patients with resected pancreatic cancer(PC)is not yet standardized.Because the prognosis differs according to the American Joint Committee on Cancer(AJCC)stage,a tailored approach to establish more aggressive treatment plans in high-risk patients is necessary.However,studies comparing the efficacy of adjuvant treatment modalities according to the AJCC stage are largely lacking.AIM To compare the efficacy of chemotherapy and chemoradiation therapy according to AJCC 8th staging system in patients with PC who underwent surgical resection.METHODS A total of 335 patients who underwent surgical resection and adjuvant treatment for PC were included.Patients were divided into three groups:Chemoradiation therapy(CRT)group,systemic chemotherapy(SCT)group and combined treatment of chemoradiation plus chemotherapy therapy(CRT-SCT)group.The primary outcomes were differences in overall survival(OS)between the three groups.The secondary outcomes were differences in recurrence-free survival,recurrence pattern and adverse events between the three groups.RESULTS Patients received CRT(n=65),SCT(n=62)and CRT-SCT(n=208).Overall median OS was 33.3 mo(95%confidence interval(CI):27.4-38.6).In patients with stage I/II,the median OS was 27.0 mo(95%CI:2.06-89.6)in the CRT group,35.8 mo(95%CI:26.9-NA)in the SCT group and 38.6 mo(95%CI:33.3-55.7)in the CRT SCT group.Among them,there was no significant difference in OS between the three groups.In 59 patients with stage III,median OS in the SCT group[19.0 mo(95%CI:12.6-NA)]and the CRT-SCT group[23.4 mo(95%CI:22.0-44.4)]was significantly longer than that in the CRT group[17.7 mo(95%CI:6.8-NA);P=0.011 and P<0.001,respectively].There were no significant differences in incidence of locoregional and distant recurrences between the three groups(P=0.158 and P=0.205,respectively).Incidences of grade 3 or higher hematologic adverse events were higher in the SCT and CRT-SCT groups than in the CRT group.CONCLUSION SCT and CRT-SCT showed significantly longer OS and recurrence-free survival than CRT in patients with AJCC stage III,while there was no significant difference in OS between the CRT,SCT and CRT-SCT groups in patients with AJCC stage I/II.Different adjuvant therapy according to AJCC stage can be applied in patients with PC.

A New Era in the Adjuvant Treatment of Pancreatic Adenocarcinoma

Pancreatic adenocarcinoma is currently a major public health problem, being the 7th cause of death worldwide. Incidence is increasing and unfortunately nowadays the incidence is almost overlapping to mortality. The cornerstone of curative treatment is still surgery, but adjuvant treatment is critical to decreasing the risk of recurrence.

Development and controversies of adjuvant therapy for pancreatic cancer

BACKGROUND: Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES: A Medline database search was performed to identify relevant articles using the keywords 'pancreatic neoplasm', and 'adjuvant therapy'. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identified. The results for adjuvant regimens based on systemic 5-fluorouracil with or without external radiotherapy were conflicting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS: Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

Preoperative serum carbohydrate antigen 19-9 levels predict early recurrence after the resection of early-stage pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a serious disease with a poor prognosis.Only a minority of patients undergo surgery due to the advanced stage of the disease,and patients with early-stage disease,who are expected to have a better prognosis,often experience recurrence.Thus,it is important to identify the risk factors for early recurrence and to develop an adequate treatment plan.AIM To evaluate the predictive factors associated with the early recurrence of earlystage PDAC.METHODS This study enrolled 407 patients with stage I PDAC undergoing upfront surgical resection between January 2000 and April 2016.Early recurrence was defined as a diagnosis of recurrence within 6 mo of surgery.The optimal cutoff values were determined by receiver operating characteristic(ROC)analyses.Univariate and multivariate analyses were performed to identify the risk factors for early recurrence.RESULTS Of the 407 patients,98 patients(24.1%)experienced early disease recurrence:26(26.5%)local and 72(73.5%)distant sites.In total,253(62.2%)patients received adjuvant chemotherapy.On ROC curve analysis,the optimal cutoff values for early recurrence were 70 U/mL and 2.85 cm for carbohydrate antigen 19-9(CA 19-9)levels and tumor size,respectively.Of the 181 patients with CA 19-9 level>70 U/mL,59(32.6%)had early recurrence,compared to 39(17.4%)of 226 patients with CA 19-9 level≤70 U/mL(P<0.001).Multivariate analysis revealed that CA 19-9 level>70 U/mL(P=0.006),tumor size>2.85 cm(P=0.004),poor differentiation(P=0.008),and non-adjuvant chemotherapy(P=0.025)were significant risk factors for early recurrence in early-stage PDAC.CONCLUSION Elevated CA 19-9 level(cutoff value>70 U/mL)can be a reliable predictive factor for early recurrence in early-stage PDAC.As adjuvant chemotherapy can prevent early recurrence,it should be recommended for patients susceptible to early recurrence.

Adjuvant and neoadjuvant therapy for pancreatic cancer

Pancreatic cancer still remains a major cause of cancer-related mortality;however,there is a slight but continuous improvement in survival over the past 2 decades.Progress in chemotherapy has contributed to the survival improvement in patients with any stage of pancreatic cancer.In this review,we summarize the currently available evidence regarding adjuvant and neoadjuvant therapy with a focus mainly on randomized controlled trial.The median overall survival in resected pancreatic cancer patients has significantly improved to 22.8 to 54.4 months with the use of adjuvant therapy from 11 to 20.2 months with a strategy of observation only.Recent data from randomized trials support the use of neoadjuvant therapy for patients with resectable or borderline resectable pancreatic cancer.But given a variety of neoadjuvant regimens and different definitions of resectability status,data should be interpreted with caution.Several other trials are ongoing and will provide further evidence.

The role of radiation for pancreatic adenocarcinoma

Pancreatic cancer is an aggressive malignancy with a high recurrence rate even after curative-intent resection.Improvements in survival have not been achieved in the last 25 years thus highlighting the need for effective multimodal treatment strategies.The role of radiation therapy for pancreatic cancer remains ill-defined due to historical lack of a standard definition of resectability,and the use of antiquated radiation delivery techniques and chemotherapy regimens.Current level I data regarding neoadjuvant chemoradiotherapy for resectable and borderline resectable pancreatic adenocarcinoma(PDAC)are limited to 2 randomized controlled trials and several retrospective studies and suggest that it may lead to an increased likelihood of a margin-negative resection and certainly allows for improved patient selection for pancreaticoduodenectomy when compared to upfront surgery.In the adjuvant setting,data are similarly lacking but suggest that chemoradiotherapy may be beneficial for patients at high risk of locoregional recurrence.Here we review existing data regarding the role of radiation in PDAC.

胰腺癌辅助治疗的争议与共识

胰腺癌预后较差,即使接受了根治性切除术,术后复发和转移风险仍然很高。因此胰腺癌术后的辅助治疗至关重要,主要策略包括化疗或同期联合放化疗。然而就目前所公布的几项Ⅲ期临床研究而言,尚不足以确立一套业界公认的胰腺癌术后辅助治疗的规范流程。北美学者依据胃肠道肿瘤研究协作组(GI Tumor Study Group,GITSG)及美国肿瘤放射治疗协作组(Radiation Therapy Oncology Group,RTOG)的多项随机临床研究结果,推荐联合放化疗;而欧洲学者则根据ESPAC-1和CONKO-001研究结果,推荐采用单纯化疗。有关吉西他滨在辅助治疗方面是否优于氟尿嘧啶(5-FU)尚待ESPAC-3研究结果证实。本文回顾了该领域主要临床研究结果,提出就获完整切除的胰腺癌患者而言,术后接受6个月的标准剂量的吉西他滨辅助化疗(CONKO-001)或参照RTOG-9740研究的术后辅助放化疗策略,均是可取方案,但最佳策略仍需待大样本临床研究结果。

胰腺癌新辅助治疗的现状与展望

对于不伴远处转移的胰腺癌,以手术为核心的综合治疗渐成为共识。目前,多项大样本回顾性临床研究已凸显新辅助治疗的价值,各权威指南也越来越重视新辅助治疗在胰腺癌中的地位。多项大型前瞻性多中心临床研究正在进行,且多数研究的初步结果均提示新辅助治疗可提高肿瘤的根治性切除率并改善生存。但新辅助治疗在胰腺癌中,特别是在可切除胰腺癌中的应用价值仍存在争议。此外,有关胰腺癌新辅助治疗的方案选择、治疗周期及术后接续的辅助方案等问题目前也尚无共识。相信随着高等级循证医学证据的不断出现,新辅助治疗将在胰腺癌中得到更广泛的应用。

胰腺癌术后辅助性放化疗的效果及预后因素分析

背景与目的:胰腺癌术后辅助治疗方案目前尚无定论,通过观察胰腺癌患者术后辅助性放疗联合化疗的总生存期(overall survival,OS)、无远处转移生存期(metastasis-free survival,MFS)及不良反应,分析影响MFS的预后因素,明确辅助性放化疗的作用。方法:回顾性分析复旦大学附属肿瘤医院于2011年12月—2018年6月收治的88例胰腺癌R0根治术后患者的临床资料。患者接受了术后辅助性放疗联合化疗,包括区域动脉灌注化疗(regional intra-arterial infusion chemotherapy,RIAC)和系统化疗,中位放疗剂量50.4 Gy,常规分割照射(1.8~2.0 Gy/次)。评估患者治疗相关不良反应及失败模式,并对可能影响MFS的预后因素进行单因素和多因素分析。结果:患者中位OS及MFS分别为27.0及19.9个月,1、3及5年OS率分别为85.1%、30.4%及24.6%;1、3年MFS率为77.5%、28.0%。患者对于放化疗耐受较好,3~4级不良反应主要为血液学毒性,无4级非血液学毒性及5级不良反应发生。58例患者发生远处转移,肝转移最为多见。单因素分析术后辅助性放疗联合RIAC患者较未联合RIAC显示出更好的MFS(25.4个月vs 14.9个月,P=0.036)。多因素分析显示,RIAC是MFS的保护性因素(HR=1.888,P=0.048)。术后辅助性放疗联合RIAC显示出降低肝转移率的趋势。结论:胰腺癌术后辅助性放疗联合化疗是安全的,疗效令人鼓舞。治疗失败以远处转移为主,肝转移多见。术后放疗联合RIAC能够明显改善患者的MFS,可作为胰腺癌术后综合治疗的一种模式。

手术联合辅助治疗与单纯手术治疗可切除胰腺癌临床疗效的Meta分析

目的：系统评价手术联合辅助治疗（术后放化疗或化疗）与单纯手术治疗可切除胰腺癌的临床疗效。 方法：以pancreatic cancer、adjuvant therapy、chemoradiotherapy、radiochemotherapy、chemotherapy、radiotherapy及胰腺癌、辅助治疗、化学治疗、放射治疗为检索词，系统检索PubMed、Embase、Science Citation Index Expanded、Cochrane Central Register of Controlled Trials 以及中国生物医学文献数据库。检索时间为建库至2016年10月。纳入比较手术治疗联合术后放化疗或化疗与单纯手术治疗可切除胰腺癌的临床随机对照试验研究（RCT），由两名文献评价员独立筛选文献和提取数据，并进行质量评价。手术治疗联合术后放化疗为治疗1组，手术治疗联合术后化疗为治疗2组，单纯手术治疗为对照组。采用倒方差法合并风险比（HR）及其相关统计量。总生存时间和无病生存时间的评价采用HR及95%可信区间，中位生存时间和1、2、5年生存率的评价采用相对危险度（RR）和95%可信区间，采用I2对异质性进行分析。 结果：最终纳入9篇文献11项RCT，累积样本量为1 482例，治疗1组238例；治疗2组545例；对照组699例。Meta分析结果：①总生存时间：治疗1组和对照组患者总生存时间比较，差异无统计学意义（HR=0.87，95%可信区间：0.56~1.17，P〉0.05）。治疗2组和对照组患者总生存时间比较，差异有统计学意义（HR=0.68，95%可信区间：0.55~0.80，P〈0.05）。②无病生存时间：治疗1组和对照组患者无病生存时间比较，差异无统计学意义（HR=0.78，95%可信区间：0.53~1.03，P〉0.05）。治疗2组和对照组患者无病生存时间比较，差异有统计学意义（HR=0.56，95%可信区间：0.45~0.67，P〈0.05）。③中位生存时间：治疗1组和对照组患者中位生存时间比较，差异有统计学意义（RR=1.82，95%可信区间：1.35~2.45，P〈0.05）。治疗2组和对照组患者中位生存时间比较，差异有统计学意义（RR=1.32，95%可信区间：1.07~1.62，P〈0.05）。④1、2、5年生存率：治疗1组和对照组患者1、2、5年生存率比较，差异均无统计学意义（RR=1.24，2.47，1.15，95%可信区间：0.72~2.12，0.82~7.41，0.71~1.84，P〉0.05）。治疗2组和对照组患者1年生存率比较，差异无统计学意义（RR=1.15，95%可信区间：0.99~1.34，P〉0.05），两组患者2、5年生存率比较，差异有统计学意义（RR=1.24，1.73，95%可信区间：1.01~1.50，1.32~2.27，P〈0.05）。 结论：与单纯手术治疗比较，手术联合术后放化疗并未改善可切除胰腺癌患者总生存时间和无病生存时间；而手术联合化疗可以延长患者总生存时间和无病生存时间。

^(60)Co外照射对大鼠5-氟尿嘧啶血胰屏障通透性的影响

目的 探讨胰腺癌综合治疗中不同剂量放射治疗对于化学治疗疗效可能产生的影响。方法 采用高效液相色谱法 (HPLC)分别测定了大白鼠经60 Co胰腺外照射 0、2、10、2 0、30、40Gy后 8h ,静注 5 氟尿嘧啶 (5 FU) (93.75mg·kg-1)在胰腺组织中的穿透比 (PR)。同行胰腺病理检查。结果 5 FU在大鼠胰腺组织中的穿透比在小剂量 (2Gy)放疗后 8h较对照组明显升高。在大剂量放疗 (≥ 10Gy)后 8h ,PR随放疗剂量的增加而增加 (相关系数r=0 .99) ,但PR均低于或与正常对照组差异无显著意义 (P <0 .0 5 )。且在 2 0Gy剂量组中胰岛细胞已出现部分退化、变性。结论 分次治疗常用剂量(2Gy)放疗后 ,同时加用化疗 ,5 FU在胰腺组织中穿透比明显升高 ,可能会取得较好的化疗效果 ,二者具协同作用。中、大剂量放疗时 (≥ 10Gy) ,急性期合并化疗 ,放射治疗在一定程度上可能会降低血胰屏障对 5 FU的通透性 ,影响化学治疗的效果。大剂量放疗时 (2 0Gy) ,急性期即可出现胰岛细胞损伤。

食管胃结合部腺癌当前临床研究开展现状与挑战

食管胃结合部腺癌发病率逐年升高,已经成为世界性重大的影响健康的问题,已完成的三期临床研究表明,局部晚期患者接受围手术期辅助化疗、放化疗能够明显改善预后,降低局部复发率。基于化疗的靶向和免疫治疗异军突起,将展现广阔的应用前景。手术决策时,首先应考虑肿瘤部位和分型,Siewert分型在世界范围内广泛使用,有助于最佳手术方式的选择。SiewertⅠ型可采取经右胸入路行部分胃切除加食管次全切除联合整个纵隔淋巴结清扫术;SiewertⅢ型遵循胃癌根治原则进行淋巴结清扫术;有关SiewertⅡ型手术淋巴结清扫范围的确定,尚未达成共识,需要进一步研究。此外,关于食管胃结合部腺癌患者腹主动脉淋巴结转移规律以及是否需要清扫腹主动脉旁淋巴结,尚需要进一步研究。

门静脉/肠系膜上静脉病理学肿瘤侵犯在胰十二指肠切除术中的临床意义

目的评估门静脉(portal vein,PV)/肠系膜上静脉(superior mesenteric vein,SMV)病理学受侵在胰腺癌行胰十二指肠切除术(pancreaticoduodenectomy,PD)中的意义以及在无PV/SMV病理学侵犯的胰腺癌患者常规行PD联合PV/SMV切除的临床价值。方法选取2013年1月1日至2017年12月31日期间在笔者所在的两家医院收治的183例行PD的胰腺癌患者,81例为PD联合PV/SMV切除,其中42例(51.9%)PV/SMV有病理学侵犯(PD+P/S+组),39例(48.1%)无病理学侵犯(PD+P/S–组);102例为未行PV/SMV切除的标准PD(PD组)。应用多因素分析来确定影响生存的预后因素,Kaplan-Meier方法估算患者的生存期。结果PD+P/S+组、PD+P/S-组和PD组患者的年龄、性别、术前血清CA19-9水平、失血量、肿瘤大小、肿瘤分期、阳性淋巴结、阳性淋巴结比率、肿瘤分化程度、神经侵犯、术后辅助化疗、手术方式及切缘状态比较差异均无统计学意义(P>0.05),PD联合PV/SMV切除组与PD组之间的并发症发生率、病死率差异均无统计学意义(P>0.05),均无再手术发生;单因素分析显示,PD+P/S+组、PD+P/S–组和PD组之间的总生存期(overall survival,OS)差异有统计学意义(P<0.001),中位生存期分别为10个月、19个月和20个月。多因素生存分析结果显示,PV/SMV肿瘤浸润深度、术后辅助化疗和肿瘤分化程度是影响患者OS的独立预后因素。结论无论是否切除PV/SMV,有PV/SMV病理学侵犯患者的OS明显较无PV/SMV侵犯者差,血管内膜受肿瘤侵犯可能是真正影响胰腺癌患者OS的原因。PV/SMV无病理学侵犯行PD联合PV/SMV切除者与仅行PD者的OS无差异,患者是否可以从常规PV/SMV切除中受益还存在争议。

胰腺癌临床研究进展:从“切除”到“治愈”

胰腺导管腺癌恶性程度极高,肿瘤相关死亡率逐年上升。尽管外科手术技术不断提高,但患者术后的5年生存率仍低于30%。近年来研究结果显示,胰腺导管腺癌是一种系统性疾病,一期切除难以彻底治愈,需要围手术期多学科治疗。随着"潜在可治愈胰腺癌"这一概念的提出,临床医师需要在术前对胰腺导管腺癌的可切除性进行准确评估,并通过新辅助放化疗、手术及辅助放化疗等多学科治疗,提高R0切除率并降低肿瘤早期转移风险。因此,对胰腺导管腺癌的治疗目标不再满足于"单纯的外科切除",而是通过围手术期多学科治疗使患者获得长期生存。本文对"潜在可治愈胰腺癌"可切除性评估、手术技术、围手术期辅助治疗等研究进展进行简要介绍。