晚期胰腺癌内科治疗的研究进展

化疗是目前晚期胰腺癌内科治疗的重要手段.吉西他滨(gemcitabine,GEM)为治疗晚期胰腺癌的一线药物,以其为基础的联合治疗方案在不断探索中,并取得一定进展.FOLFIRINOX方案成为首个经选择患者的、疗效优于GEM的非GEM方案.随着研究的深入,多种靶向药物的出现(包括细胞毒药物或生物靶向药物)给胰腺癌的治疗带来了希望.本文将对胰腺癌的化疗和靶向治疗作一总结,以供临床参考.     

胰腺癌2061例外科手术的疗效与预后分析

目的 单中心研究胰腺癌的手术治疗效果及相关因素分析.方法 回顾性分析长海医院胰腺外科2000年1月至2011年12月诊治的2061例胰腺癌患者的诊治情况和临床数据,并对患者进行随访,随访截止至2012年9月30日.结果 所有收治的胰腺癌患者中,根治性手术治疗1657例(80.4％),姑息性手术治疗271例(13.1％),剖腹探查活检133例.根治性切除组1、3、5年生存率分别为60.3％、21.1％、10.9％,术后中位生存时间为19.6个月,其中180例患者术后存活超过5年;姑息性手术组术后中位生存时间为7.2个月.胰腺癌患者手术切除率和术后3年生存期分别由2000年至2003年的75.3％和12.4％提高到2008年至2009年的82.5％和22.1％.通过Cox回归模型发现,大血管侵犯、淋巴结转移、神经浸润以及肿瘤分化程度是胰腺癌预后的独立影响因素.结论 手术是目前胰腺癌治疗的唯一有效手段,随着手术方式和围手术期治疗的进步,胰腺癌的手术病死率和并发症发生率明显下降,术后生存率逐步提高.     

胰腺癌分子靶向治疗的研究进展

胰腺癌是预后最差的恶性肿瘤之一,发病与西方化饮食、吸烟、饮酒、肥胖、慢性胰腺炎及胰腺癌家族史等因素有关。目前,胰腺癌的治疗以手术及化疗为主,但疗效并不理想,了解胰腺癌发病的具体分子机制能更好的预防和治疗胰腺癌。介绍了胰腺癌发病的具体分子机制及其靶向治疗的最新进展。认为在传统治疗的基础上辅以分子靶向药物治疗有助于改善胰腺癌患者的预后。     

70岁及以上不可切除的胰腺癌患者生存因素分析

目的 探讨影响70岁及以上不可切除的胰腺癌患者生存的相关因素.方法 总结57例70岁及以上的晚期胰腺癌住院患者的临床资料,分析性别、年龄、既往糖尿病史、胆道疾病史、吸烟史、化疗、放疗、美国东部肿瘤协作组(Eastern Collaborative Oncology Group,ECOG)评分、肿瘤标志物癌胚抗原(carcinoembroynic antigen,CEA)和CA199升高情况等对总生存的影响.结果 性别、行为状态、化疗、放疗与生存密切相关.男性和女性比较,中位生存期分别为(10.7±5.4)个月和(5.5±2.3)个月,P=0.000;ECOG评分0～1分和≥2分比较,中位生存期分别为(10.1±5.8)个月和(7.3±3.8)个月,P=0.040;未接受化疗组和接受化疗组比较,中位生存期分别为(7.8±5.3)个月和(11.5±5.0)个月,P=0.038;未接受放疗组和接受放疗组比较,中位生存期分别为(8.9±5.4)个月和(13.7±3.8)个月,P=0.048;差异均有统计学意义.胰腺癌总的中位生存期为8.9个月,1年生存率为28.1%.结论 70岁及以上老年人胰腺癌的预后与性别、行为状态、化疗和放疗相关.对于不可切除但行为状态好的老年胰腺癌患可以考虑化疗,部分患者甚至可以考虑联合放疗.     

陀螺刀治疗胰腺癌的疗效观察

目的探讨陀螺刀治疗胰腺癌的近期疗效和毒副作用。方法采用国产陀螺刀治疗胰腺癌58例,用50%～60%等剂量曲线包绕靶区,全组周边处方剂量3 500～4 200 cGy,中位处方剂量3 800 cGy,350 cGy/次,5次/周,对其近期疗效及毒副作用进行总结。结果 58例患者中完全缓解10例(17.24%),部分缓解21例(36.21%),稳定20例(34.48%),进展7例(12.07%),总有效率为53.45%,1 a局部控制率为36.21%,1 a总生存率为62.07%。结论陀螺刀治疗胰腺癌的初期疗效较好,毒副作用较低,但其远期疗效尚需进一步观察。     

70岁及以上不可切除的胰腺癌患者生存因素分析

Objective To explore the effect of related factors on survival of patients with unresectable pancreatic cancer aged 70 years and over. Methods Fifty-seven patients with unresectable locally advanced or metastatic pancreatic cancer aged 70 years and over were enrolled.Their survival time were analyzed with SPSS 13.0 by taking account of gender, age, smoking history,alcohol history, pancreatic disease history, diabetes mellitus history, Eastern Collaborative Oncology Group (ECOG) scoring, chemotherapy, radiotherapy, CEA and CA199 levels. Results Gender,ECOG scoring, chemotherapy and radiotherapy had relationship with overall survival. The median survival time was 8.9 months and one-year survival rate was 28.1%. The median survival was (10.7±5.4) months in male group and (5.5±2.3) months in female group (P=0.000). The median survival was(10.1±5.8) months in patients with ECOG 0～1 group and(7.3±3.8)months in patients with ECOG 2 group (P=0.040). The median survival was(7.76±5.27) months in nochemotherapy group and(11.5±5.0)months in chemotherapy group (P=0.038). The median survival was(8.87±5.36)months in no radiotherapy group and (13.7±3.8) months in radiotherapy group (P=0.048). Conclusions The patients who have better ECOG performance status and receive chemotherapy or radiotherapy show better survival.     

70岁及以上不可切除的胰腺癌患者生存因素分析

Objective To explore the effect of related factors on survival of patients with unresectable pancreatic cancer aged 70 years and over. Methods Fifty-seven patients with unresectable locally advanced or metastatic pancreatic cancer aged 70 years and over were enrolled.Their survival time were analyzed with SPSS 13.0 by taking account of gender, age, smoking history,alcohol history, pancreatic disease history, diabetes mellitus history, Eastern Collaborative Oncology Group (ECOG) scoring, chemotherapy, radiotherapy, CEA and CA199 levels. Results Gender,ECOG scoring, chemotherapy and radiotherapy had relationship with overall survival. The median survival time was 8.9 months and one-year survival rate was 28.1%. The median survival was (10.7±5.4) months in male group and (5.5±2.3) months in female group (P=0.000). The median survival was(10.1±5.8) months in patients with ECOG 0～1 group and(7.3±3.8)months in patients with ECOG 2 group (P=0.040). The median survival was(7.76±5.27) months in nochemotherapy group and(11.5±5.0)months in chemotherapy group (P=0.038). The median survival was(8.87±5.36)months in no radiotherapy group and (13.7±3.8) months in radiotherapy group (P=0.048). Conclusions The patients who have better ECOG performance status and receive chemotherapy or radiotherapy show better survival.     

与胰腺癌神经浸润相关的临床因素分析

目的 观察胰腺癌的神经浸润状况,分析与其相关的临床因素.方法 回顾性分析73例胰腺癌患者的神经浸润状况,分析神经浸润与肿瘤临床病理特征及患者生存率之间的关系.结果 73例中38例(52.1％)有神经浸润,其中6例(15.8％)为单纯胰内神经浸润,32例(84.2％)为胰内、胰外神经均浸润.神经浸润与患者性别、年龄及肿瘤病理类型、分化程度、大小、淋巴结转移均无关(P值均＞0.05),而与腹痛、脉管浸润、肿瘤组织表皮生长因子受体(EGFR)及血管内皮生长因子(VEGF)表达均显著相关(P值均＜0.01).有神经浸润患者的中位生存时间为8个月,显著短于无神经浸润患者的13个月(x2=4.69,P=0.030).结论 胰腺癌的神经浸润发生率较高,可引起明显腹痛,其与脉管浸润及肿瘤组织EGFR和VEGF表达相关,是影响胰腺癌患者术后生存率的因素之一.     

晚期重症结核性脑膜炎疗效分析

结核性脑膜炎 (简称结脑 )预后的关键在于早期诊断和早期治疗。但由于医疗条件和医疗技术受限 ,使许多结脑患者不能及时就医或确诊 ,而使病情渐进性发展至晚期 ,以致失去良好的治疗机会。为探讨晚期重症结脑的疗效及预后 ,特将 1993年以来我科收治的重症结脑总结如下。1　资料与方法1.1　一般资料 :重症结脑 10 6例 ,均为早期未能明确诊断者 ,误诊时间 18～ 4 0天 ,平均 2 9天 ;其中男性 70例 ,女性 36例 ;年龄 18～ 4 2岁 ,平均 30岁。1.2　临床表现 :10 6例患者入院时均有不同程度发热、颈项强直、瘫痪、意识障碍等表现。详见下表。表 1　…     

胰腺癌相关抗原的免疫组化分析

用抗人胰腺癌单克隆抗体B6（MAbB6)对胰腺癌相关抗原进行了大量组织切片的ABC免疫组化染色。结果示MAbB6与31（31／33）例胰腺癌组织有阳性染色，23（23／33）例为强阳性，2（2／33）例为阴性。阳性染色主要见于胰腺癌细胞的胞膜。MAbB6与少数其他肿瘤组织，良性疾病组织及正常组织也有一定的阳性染色，其中与6（6／8）例慢性胰腺炎组织呈阳性染色，2（2／8）例为强阳性染色，以上结果说明MAbB2对胰腺癌组织有较强的亲和力和较高的特异性，它所针对的抗原是一种胰腺癌细胞膜抗原，呈非特异性分布。慢性胰腺炎和胰腺癌有共同的抗原表达，两者之间的关系有待进一步的探讨。     

Cryosurgery with combination of (125)iodine seed implantation for the treatment of locally advanced pancreatic cancer

OBJECTIVE: To study the therapeutic value of cryosurgery with combination of (125)iodine seed implantation for locally advanced pancreatic cancer. METHODS: Thirty-eight patients with locally advanced pancreatic cancer were enrolled in this study. The diagnosis was confirmed by pathology in 31 patients. Ten patients had metastases of the peripancreatic lymph node and eight had liver metastases. The therapy included cryosurgery, which was performed intra-operatively or percutaneously under guidance of ultrasound and/or computed tomography (CT), and (125)iodine seed implantation, which was performed during cryosurgery process or post-cryosurgery under the guidance of ultrasound and/or CT. RESULTS: Eleven patients received intra-operative cryosurgery and 27 received percutaneous cryosurgery. Fourteen patients underwent two procedures of cryosurgery and three underwent three procedures of cryosurgery. (125)Iodine seed implantation was performed during the freezing procedure in 29 patients and within 3-7 days after cryosurgery in nine patients under ultrasound and CT guidance. Fifteen patients, of whom 13 had metastases of peripancreatic lymph nodes or liver received regional chemotherapy. At 3 months after therapy, a CT follow-up was performed to estimate the tumor response to therapy. Most of the patients had varying degrees of tumor necrosis. A complete response of the tumor was seen in 23.6% of patients, a partial response in 42.1%, stable disease in 26.3% and progressive disease in 7.9%. The adverse effects associated with cryosurgery mainly included pain of the upper abdomen and increased serum amylase activity. Acute pancreatitis was seen in five patients, one of whom presented a severe type of pancreatitis. During the followed-up of a median of 16 months (range of 5-37) median overall survival was 12 months, 19 patients (50.0%) survived for 12 months or longer and four survived for 24 months or longer. CONCLUSION: As it is far less invasive than conventional pancreas resection and entails a low rate of adverse effects, cryosurgery should be the choice modality for most patients with locally advanced pancreatic cancer. (125)Iodine seed implantation can destroy residue survival cancer cells after cryosurgery. Hence, combination of both modalities has a complementary effect.     

Survival analysis of pancreatic and periampullary collision cancers

OBJECTIVE: Collision cancers are malignancies in the same organ or anatomical site that comprises at least two different tumor components, with no mixed or transitional area between two components. Collision cancers are very rare in the pancreas and periampullary region. The aim of this study was to analyze the clinical and pathological features and prognosis of collision cancer in the pancreas and periampullary region. METHODS: Patients with collision cancers of the pancreas and periampullary region (n= 10) who had undergone radical surgery were retrospectively studied. Their clinical and pathological features were summarized and the prognostic data were compared with patients with pancreatic adenocarcinomas who underwent radical surgery (n= 87) and with patients with pancreatic or periampullary malignancies who underwent palliative surgery (n= 89). RESULTS: Compared with other cancers at these sites, collision cancer presents no specific clinical features. However, the median survival period of patients with such malignancies was only 10.0 months, which was much less than those with pancreatic adenocarcinomas who underwent radical surgery (27.0 months) and those who received a palliative operation (20.9 months) only. CONCLUSION: Collision cancers of the pancreas and periampullary region are difficult to diagnose preoperatively. Their prognosis is poor even after radical resection and adjuvant chemotherapy were given.     

老年进展期胰腺癌98例临床研究

目的探讨进展期胰腺癌不同的治疗方法对预后的影响，以达到治疗的最优化。方法回顾性分析2002年11月至2005年9月收治的98例进展期胰腺癌，分为手术组（81例）：手术[行胆系和（或）肠系转流术、活检术等]加或不加辅助治疗；非手术组（17例）：行非手术治疗；并分析其治疗效果。结果手术组并发症发生率为17．3％（14／81）、病死率为4．9％（4／81），生存期平均为（2．9±2．3）年，加或不加辅助治疗其生存期分别为（2．9±3．7）年、（2．8±3．1）年；非手术组无并发症和死亡，生存期平均（2．7±2．1）年。结论对进展期无法行根治性切除术的胰腺癌、姑息性切除是无益的，对伴发胆系和（或）肠系梗阻时行转流术是必须的，围手术期辅助治疗是改善预后的重要方法。     

Prognostic factors in definitive radiochemotherapy of advanced inoperable esophageal cancer

The aim of this study was to assess the efficacy and prognostic factors of definitive radiochemotherapy (RCT) for inoperable esophageal cancer. Between 1995 and 2005 all patients with inoperable esophageal cancer that underwent concurrent RCT were included in this retrospective study. Conventional computed tomography-based treatment planning as well as 3D-conformal radiotherapy (RT) was used. Maximum radiotherapy dose was 63 Gy. Chemotherapy consisted of cisplatin (20 mg/m(2) d1-5 and 29-33) and 5-FU (650-1000 mg/m(2) d1-5 and 29-33). Patients not suitable for RCT received radiotherapy alone. Toxicity was measured according to common toxicity criteria (CTC). Two hundred three consecutive patients with inoperable esophageal cancer that received definitive therapy were identified in this time period (160 with squamous cell carcinoma and 43 with adenocarcinoma). The 2-year overall survival probability was 21.2% whereas the progression-free survival at 2 years was 13.8% for all patients. In the univariate analysis, type of histology, T-stage, N-stage, application of chemotherapy, and the radiation dose were significantly correlated with overall/progression-free survival. Moreover, multivariate analysis revealed an independent prognostic impact for N-stage, radiation dose, and concurrent chemotherapy. Definitive RCT is an important palliative treatment option for patients with inoperable esophageal cancer. N-stage, radiation dose, and concurrent chemotherapy are important prognostic factors for survival.     

AKT2在胰腺癌组织中的表达及意义

目的 探讨胰腺癌组织中蛋白激酶B（AKT）2的表达及其在胰腺癌发生、发展中的作用。方法 采用免疫组化SABC法检测63例胰腺癌组织和23例胰腺良性病变组织中AKT2的表达,分析其与胰腺癌临床病理因素的关系。结果 AKT2在胰腺癌组织中的阳性表达率为39．7％（25／63）,明显高于胰腺良性病变组织的13％（3／23）,P〈0．05。AKT2表达与胰腺癌组织学分级、淋巴结转移、TNM分期有关（P〈0．05）。结论 AKT2在胰腺癌组织中表达增高,可能在胰腺癌发生、发展、转移中起重要作用。     

Prognostic factors for long-term survival in patients with locally invasive pancreatic cancer

Background/Purpose

We aimed to investigate predictors of survival in patients with resectable locally invasive pancreatic cancer.

Methods

The patient cohort consisted of 55 patients with locally invasive pancreatic cancer (International Union Against Cancer [UICC] stage III in 36 patients and stage IV in 19) who had undergone resection. The patients were informed about the advantages and the adverse effects of postoperative chemotherapy, and prospectively selected either observation alone or postoperative chemotherapy. The postoperative chemotherapy regimen options were: (1) intraarterial chemotherapy alone, (2) systemic chemotherapy alone, or (3) intraarterial chemotherapy combined with systemic chemotherapy.

Results

Overall 1-year and 2-year survival rates after resection were 40.5% and 13.5%, respectively. Median survival time was 10.9 months. Twenty-nine patients (52.7%) received postoperative chemotherapy. On univariate analysis, only postoperative chemotherapy was associated with long-term survival (P < 0.01). In the patients with postoperative chemotherapy, the 1-year survival rate and MST were 61.7% and 16.3 months, compared with 20.1% and 7.9 months in the patients without postoperative chemotherapy. Multivariate analysis also showed that only postoperative chemotherapy was identified as an independent survival factor.

Conclusions

It was suggested that postoperative chemotherapy was essential for the improvement of survival in patients with locally invasive pancreatic cancer.

     

Treatment of locally advanced pancreatic cancer with irreversible electroporation – a Danish single center study of safety and feasibility

Objectives: Irreversible electroporation (IRE) is a novel non-thermal ablative technique applied in the treatment of unresectable locally advanced pancreatic cancer (LAPC). This paper reports on the initial experience with IRE of unresectable LAPC in our institution.

Methods: From October 2013 to March 2018, patients with unresectable LAPC referred for IRE at the Department of Gastrointestinal Surgery, Aalborg University Hospital, were considered for inclusion in the study. Ninety-day morbidity, 30-day mortality, pain score, length of hospital stay (LOS) and overall survival (OS) were recorded.

Results: We included 33 patients receiving 40 IRE ablations in total. The median visual analogue scale (VAS)-score was four (range 0–10) two hours after IRE, and one (range 0–8) eight hours after IRE. The median LOS was one day (range 1–13 days). Post-procedural complications occurred in 21 of 40 ablations (53%), of which eight (20%) were major (Clavien–Dindo grade III or more). A proportion of the observed complications might be attributed to disease progression and not IRE per se. Although not statistically significant, we observed increased severity of complications in tumors above 3.5?cm. The 30-day mortality was 5% (2/40). The median OS was 10.7 months (range 0.6–53.8 months) from the initial IRE procedure, and 18.5 months (range 4.9–65.8 months) from time of diagnosis.

Conclusions: In our institution, IRE seems as a feasible consolidative treatment of unresectable LAPC with an acceptable safety profile. The oncological outcome of IRE in patients with unresectable LAPC is to be further evaluated in a planned phase 2 clinical trial (CHEMOFIRE-2).     

The European organization for research and treatment of cancer quality of life questionnaire: implications for prognosis in pancreatic cancer

Background The goal of this study was to evaluate the association between patient quality of life (QoL) and survival in pancreatic cancer patients undergoing care in a community hospital comprehensive cancer center. Patients and Methods A consecutive case series of 55 histologically confirmed pancreatic cancer treated at Cancer Treatment Centers of America? at Midwestern Regional Medical Center was studied between 04/01 and 11/04. The EORTC QLQ-C30 was utilized to assess patient QoL. Kaplan–Meier method was used to calculate survival. Log-rank test was used to study the equality of survival distributions. Multivariate Cox regression analyses were then performed to evaluate the joint prognostic significance of those QoL and clinical factors that were shown to be prognostic upon univariate analyses. Results Of the 55 patients, 28 were newly diagnosed and 27 had prior treatment history. The median age was 55 years (range 33–74 years). Majority (34) had stage IV disease at diagnosis. The QLQ-C30 parameters to show statistically significant associations with survival were physical, role, and emotional functioning scales and fatigue, appetite loss, constipation, and diarrhea symptom scales. Conclusions We found that patient QoL, as measured by the QLQ-C30 physical functioning scale, provides useful prognostic information, independent of multiple cancer symptoms, in patients with pancreatic cancer. While these findings require further investigation in large patient cohorts, they may have important implications for patient stratification in clinical trials, as well as aid in clinical decision making.     

The treatment and survival of elderly patients with locally advanced pancreatic cancer: A post-hoc analysis of a multicenter registry

BackgroundThe treatment options for patients with locally advanced pancreatic cancer (LAPC) have improved in recent years and consequently survival has increased. It is unknown, however, if elderly patients benefit from these improvements in therapy. With the ongoing aging of the patient population and an increasing incidence of pancreatic cancer, this patient group becomes more relevant. This study aims to clarify the association between increasing age, treatment and overall survival in patients with LAPC.MethodsPost-hoc analysis of a multicenter registry including consecutive patients with LAPC, who were registered in 14 centers of the Dutch Pancreatic Cancer Group (April 2015–December 2017). Patients were divided in three groups according to age (<65, 65–74 and ≥75 years). Primary outcome was overall survival stratified by primary treatment strategy. Multivariable regression analyses were performed to adjust for possible confounders.ResultsOverall, 422 patients with LAPC were included; 162 patients (38%) aged <65 years, 182 patients (43%) aged 65–74 and 78 patients (19%) aged ≥75 years. Chemotherapy was administered in 86%, 81% and 50% of the patients in the different age groups (p<0.01). Median overall survival was 12, 11 and 7 months for the different age groups (p<0.01).Patients treated with chemotherapy showed comparable median overall survival of 13, 14 and 10 months for the different age groups (p=0.11). When adjusted for confounders, age was not associated with overall survival.ConclusionElderly patients are less likely to be treated with chemotherapy, but when treated with chemotherapy, their survival is comparable to younger patients.     

A patient with unresectable advanced pancreatic cancer achieving long-term survival with Gemcitabine chemotherapy

A 68-year-old female visited a local clinic with epigastralgia. A routine laboratory test revealed jaundice and liver dysfunction. She was referred to this hospital. Abdominal computed tomography （CT） and endoscopic retrograde cholangio-pancreatography （ERCP） revealed that the density of the entire pancreas had decreased, and showed dilatation of the common bile duct （CBD） and the main pancreatic duct （MPD）. Pancreatic cancer was diagnosed by cytological examination analyzing the pancreatic juice obtained by ERCP. When jaundice had decreased the tumor was observed via laparotomy. No ascites, liver metastasis, or peritoneal dissemination was observed. The entire pancreas was a hard mass, and a needle biopsy was obtained from the head, body and tail of the pancreas. These biopsies diagnosed a poorly differentiated adenocarcinoma. Hepaticojejunostomy was thus performed, and postoperative progress was good. Chemotherapy with 1000 mg/body per week of gemcitabine was administered beginning 15 d postoperatively. However, the patient suffered relatively severe side effects, and it was necessary to change the dosing schedule of gemcitabine. Abdominal CT revealed a complete response （CR） after 3 treatments. Therefore, weekly chemotherapy was stopped and was changed to monthly administration. To date, for 4 years after chemotherapy, the tumor has not reappeared.