血管内皮生长因子C与胰腺癌根治术后复发的相关性研究

目的 探讨血管内皮生长因子C(VEGF-C)表达及多种临床病理因素在预测胰腺癌根治术后复发的价值.方法 应用Envision免疫组化法测定47例胰腺癌根治性切除标本中胰腺癌组织和自身胰腺正常组织中VEGF-C的表达.通过Kaplan-Meier生存分析和Cox风险比例模型,评估VEGF-C和各临床病理因素对胰腺癌根治术后复发的影响.结果 VEGF-C在胰腺癌组织中的表达比例及其在自身正常胰腺组织中的表达比例分别为29例(61.7%)、7例(14.9%),VEGF-C在胰腺癌组织中的表达比例明显高于其在自身正常胰腺组织中的表达(P=0.018).胰腺癌根治术后患者无病中位生存期为11.9个月,平均为(18.4±2.4)个月.1年、2年、3年累计无病生存率分别为46.8%、23.4%和14.4%.VEGF-C的表达与淋巴结转移有显著的相关性(P=0.036).单因素生存分析显示VEGF-C(P=0.020)、肿瘤直径(P=0.013)、年龄(P=0.057)、术后辅助化疗(P=0.017)与无病生存期明显相关.Cox回归多因素分析显示,VEGF-C(P=0.009),肿瘤直径(P=0.010)、术后辅助化疗(P=0.017)是胰腺癌根治术后患者无病生存期独立的预后因素.结论 VEGF-C在胰腺癌组织中表达明显增高,VEGF-C的表达与淋巴结转移有显著的相关性,VEGF-C可作为判断胰腺癌根治术后患者无病生存期的独立指标.

Abstract：

Objective To investigate the prognostic value of vascular endothelial growth factor C (VEGF-C) and clinicopathologic indexes in predicting recurrence following curative resection of pancreatic cancer. Methods The expressions of VEGF-C of 47 patients who underwent curative resection for curative pancreatic cancer resection were detected by Envision immunohistochemical methods. The effects of VEGF-C and clinicopathologic indexes on recurrence were assessed by the Kaplan-Meier and Cox proportional hazards model. Results The positive rates of VEGF-C were 61. 7% in = 29) and 14. 9%(n = 7), respectively, in pancreatic cancer and normal pancreatic tissues. The positive expression of VEGF-C in pancreatic carcinoma was obviously higher than the normal pancreatic tissues (P = 0. 018). The median disease-free survival time was 11. 9 months, the average disease-free survival time was 18. 4 + 2. 4 months, and the cumulative 1-year, 2-year and 3-year actuarial recurrence free survival rates were 46. 8%, 23. 4%, 14. 4%, respectively. There was a significant correlation between the VEGF-C expression and lymph node metastasis in pancreatic cancer (P = 0. 036). On Kaplan-Meier analysis, VEGF-C (P = 0. 020), tumor diameter (P = 0. 013), age (P = 0. 057) and adjuvant chemotherapy (P=0. 017) were associated with disease-free survival time. Multivariate analysis showed VEGF-C (P = 0. 009), tumor diameter (P = 0. 010) and adjuvant chemotherapy (P = 0. 017)were independent prognostic factors of disease-free survival after surgery for pancreatic cancer.Conclusion The expression of VEGF-C was higher in pancreatic cancer, and VEGF-C was correlated with lymph node metastasis. VEGF-C was the biomarker that independently predicted disease-free survival after surgery for pancreatic cancer.     

Resection and radiochemotherapy of pancreatic cancer – the future?

Background: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. The controversies among those being pro and contra adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. Patients/Methods: The literature regarding the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. The biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities was focussed on, to characterise the disease for an optimally targeted treatment in conjunction with surgical removal of the tumour. The results of systemic and regional chemotherapy and radiotherapy, either alone or in combination, before, during and after surgery were critically analysed with respect to the oncological possibilities and pitfalls of each treatment method. Results: In two randomised trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy, the adjuvant treatment achieved a significant prolongation of the median survival time. The 5-year and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy , the survival times were improved compared with surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalising margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. Conclusions: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being indecisive or against adjuvant therapy, the participation in trials, e.g. the ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested against surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy. Received: 13 February 1998     

Combined resection of aberrant right hepatic artery without anastomosis in panceaticoduodenectomy for pancreatic head cancer: A case report

IntroductionThis case report is intended to inform pancreas surgeons of our experience in operative management of aberrant pancreatic artery.Presentation of caseA 63-year-old woman was admitted to our institute’s Department of Surgery with obstructive jaundice, and the pancreas head tumor was found. To improve liver dysfunction, an endoscopic retrograde nasogastric biliary drainage tube was placed in the bile duct. Endoscopic fine-needle aspiration showed a pancreas head carcinoma invading the common bile duct, the aberrant right hepatic artery arising from the superior mesenteric artery, and the portal vein. Enhanced computed tomography showed the communicating artery between the right and left hepatic artery via the hepatic hilar plate. By way of imaging preoperative examination, a pancreaticoduodenectomy combined resection of the aberrant right hepatic artery and portal vein was conducted without arterial anastomosis. Hepatic arterial flow was confirmed by intraoperative Doppler ultrasonography, and R0 resection without tumor exposure at the dissected plane was achieved. The patient’s postoperative course was uneventful.DiscussionIn this case report, perioperative detail examination by imaging diagnosis with respect to hepatic arterial communication to achieve curative resection in a pancreas head cancer was necessary. Non-anastomosis of hepatic artery was achieved, and the necessity of R0 resection was stressed by such management.ConclusionBy the preoperative and intraoperative imaging managements conducted, combined resection of the aberrant right hepatic artery without anastomosis was achieved by pancreaticoduodenectomy for pancreas head cancer. However, improvements in imaging diagnosis and careful management of R0 resection are important.     

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.     

Survival benefits of portal vein resection for pancreatic cancer

BACKGROUND: The efficacy of portal vein resection for pancreatic cancer is controversial. METHODS: Eighty-one consecutive patients with pancreatic cancer undergoing surgical resection were retrospectively analyzed. The clinicopathological findings and relationship between portal vein resection and survival were investigated. RESULTS: Thirty-three patients with pancreatic cancer underwent pancreatic resection with portal vein resection. Histological examination revealed that 17 patients had definite invasion to the portal vein (group 1) and 16 patients had no invasion (group 2). Forty-eight patients with pancreatic cancer underwent pancreatic resection without portal vein resection (group 3). There were no significant differences in survival rates (P = 0.437) between patients with portal vein resection and patients without portal vein resection. However, patients in group 1 had a significantly (P = 0.021) worse prognosis as compared with those in group 2. Despite aggressive surgical resection, the surgical margin was positive in 35% of patients in group 1 as compared with 13% of patients in group 2 and 21% of patients in group 3. CONCLUSIONS: Patients undergoing portal vein resection for pancreatic cancer had a prognosis similar to patients without portal vein resection. Negative microscopic invasion to the portal vein was significantly associated with improved survival.     

R2 resection in pancreatic cancer—does it make sense?

Background  The goal of surgical treatment in patients with pancreatic cancer is the complete resection of tumor tissue; however, the intraoperative appraisal of resectability can be difficult. Extensive surgical exploration for definitive clear resectability may lead to R2 resections in single cases. Patients  We analyzed 38 patients with pancreatic cancer with remaining macroscopic tumor tissue after pancreatic resection, as R0 resection was not possible. Patients were compared to 46 patients with unresectable cancer without distant metastases or peritoneal carcinomatosis, in which a bypass procedure was performed. Results  Operating time and hospital stay were significantly longer after R2 resection. Intraoperative blood loss was significantly higher; and severe surgical complications and the need for relaparotomy were significantly more frequent after R2 resection. The 30-day mortality rate was higher after R2 resection; this difference was not statistically significant. Median survival was comparable in both groups. Two years after surgery, 22.6% of the patients after R2 resection were still alive compared to 10.9% after bypass surgery. Conclusion  Tumor debulking is not a treatment option in patients with advanced pancreatic cancer, but the patient is not at a disadvantage compared to bypass procedures if tumor tissue remains and R0 resection cannot be achieved after surgical exploration.     

Hot topics in pancreatic cancer management

Pancreatic ductal adenocarcinoma(PDAC) is a sneaky and lethal disease burdened by poor prognosis. PDAC is often detected too late to be successfully cured, and it has been estimated that it will be a leading cause of cancer-related deaths in the near future. During the last decade, multimodal treatments involving surgery, chemotherapy and radiotherapy have contributed to improving the prognosis of this disease; however, long-term results are still not satisfactory. Postoperative morbidity and mo...     

The challenge of pancreatic cancer

Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in men and women in the United States. It affects nearly as many people each year as does the human immunodeficiency virus and has a much worse outcome. This article reviews the progress in treatment of this disease since 1975, outlines the current clinical and research challenges in the field, and suggests a plan of action to address these challenges. The world literature in the field since 1975 was reviewed, and the pancreatic cancer Progress Report Group of the National Cancer Institute (NCI) is reviewed and presented. Some progress has been made in understanding and treating pancreatic cancer since 1975. Much remains to be done. The lack of progress in the field can largely be attributed to the lack of importance and subsequent lack of research dollars attributed to it by the NCI. The NCI is addressing this issue by proposing to fund Specialized programs of research excellence grants in pancreatic cancer. In addition, other mechanisms exist within the NCI to allow for additional funding of pancreatic cancer. Using the tremendous progress made in the field of human immunodeficiency virus research as an example, it is hoped that similar improvements can be made in the field of pancreatic cancer if substantial and sustained efforts are made.     

Debate: extended resection for pancreatic cancer; the affirmative case

Background/Purpose. A clinical study was carried out to clarify the indications for extended resection of pancreatic cancer. Methods. From July 1981 to April 2000, 200 of 314 (63.7%) patients with pancreatic cancer underwent extended tumor resection. Portal vein resection was performed in 146 of the 200 (73%) resected cases. The postoperative survival rate was studied based on the operative and histopathological findings. Results. Operative death (within 30 days postoperatively) occurred in 11 of the 200 (5.5%) resected patients. Most of the patients who survived for 2 or 3 years were in the group with carcinoma-free surgical margins. Conclusion. The most important indication for an extended operation combined with portal vein resection for pancreatic cancer is the likelihood of obtaining surgical cancer-free margins. There is no indication for an extended resection in patients in whom the surgical margins will become cancer-positive if such a resection is employed. Received: August 12, 2002 / Accepted: August 24, 2002 RID="*" ID="*" Offprint requests to: A. Nakao     

The impact of pylorus-preserving pancreatoduodenectomy on surgical treatment for cancer of the pancreatic head

Pylorus-preserving pancreatoduodenectomy (PPPD) was reintroduced in 1978. This pylorus-preserving modification was designed to minimize complications related to gastric resection, such as early satiety, marginal ulceration, and bile reflux gastritis, as well as diarrhea and dumping. Since 1978, PPPD has been performed preferentially for benign and malignant diseases of the periampullary region and pancreatic head. Some groups have argued against PPPD for cancer of the pancreatic head, because the pylorus-preserving procedure is likely to compromise the field of resection and does not allow lymph node dissection of the peripyloric and perigastric groups. However, comparative survival rates after PPPD have been the same as, or better than, those with classic pancreatoduodenectomy, showing the rationale for PPPD as a radical resection procedure for cancer of the pancreatic head. PPPD can be performed with low mortality. Delayed gastric emptying, which is the most common complication in the immediate postoperative period after PPPD, is always transient. Many investigators have shown that body weight and the majority of nutritional parameters are better than after PD. PPPD does not appear to cause any negative outcomes. We conclude that PPPD is the surgical procedure of choice for cancer of the head of the pancreas. Received: April 13, 2001 / Accepted: June 6, 2001     

Surgical palliation in patients with pancreatic cancer

Background The aim of palliative strategies in patients with pancreatic cancer is the relief of tumor-associated symptoms such as biliary and duodenal obstruction and tumor growth. Due to high mortality and morbidity rates of surgery, treatment of patients with advanced pancreatic cancer is mainly in the hand of gastroenterologists. Rationale In recent years, surgery of pancreatic cancer in specialized centres developed strongly, which makes it a viable option even in the treatment of advanced disease. Conclusion We advocate for an aggressive strategy in the treatment of pancreatic cancer with surgical exploration and tumor resection whenever possible.     

Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings

The autopsy findings of patients who died of recurrence after curative resection of pancreatic cancer may afford a reliable guide to increase long-term survival after surgery. Recurrence patterns were analyzed for 27 autopsied patients who had undergone potentially curative resection of pancreatic cancer. The pattern of recurrence was classified as follows: (1) local recurrence, (2) hepatic metastasis, (3) peritoneal dissemination, (4) para-aortic lymph node metastasis, and (5) distant metastasis not including hepatic metastasis, peritoneal dissemination, and para-aortic lymph node metastasis. Of the 27 autopsied patients, recurrence was confirmed for 22 of 24 patients, except for three who died of early postoperative complications. Eighteen (75%) of the 24 patients had local recurrence, 12 (50%) had hepatic metastasis, and 11 (46%) had both. For four patients, local recurrence confirmed by autopsy was undetectable by computed tomography, because the recurrent lesions had infiltrated without forming a tumor mass. Peritoneal dissemination, para-aortic lymph node metastasis, and distant metastasis were found for eight (33%), five (21%), and 18 (75%) of the cases, respectively. Twenty patients died of cancer, but local recurrence was judged to be the direct cause of death of only four. Local recurrence frequently occurs, but is rarely a direct cause of death, and most patients died of metastatic disease. Therefore, treatment that focuses on local control cannot improve the survival of patients with resectable pancreatic cancer, and thus, treatment regimens that are effective against systemic metastasis are needed.     

Long-term outcomes of extended radical resection combined with intraoperative radiation therapy for pancreatic cancer

Background/Purpose  Systemic and/or local recurrence often occurs even after curative resection for pancreatic cancer (PC). To prevent local relapse we adopted an extended radical resection combined with intraoperative radiation therapy in patients with PC, and all the patients were followed for more than 5 years. Methods  We assessed the long-term outcomes of 41 patients who underwent this combined therapy. The cumulative survival curve in this series was depicted using the Kaplan-Meier method. Statistical analyses were performed using the logrank test. Results  The actual 5-year survival rate was 14.6%, with a median survival time of 17.6 months. Six patients have been 5-year survivors. Local recurrence occurred in only 2 patients (5.0%). Cancer-related death occurred in 32 patients, 18 of whom had liver metastases. The patients with liver metastases had a significantly shorter survival time than those with other cancer-related causes of death. Patients with n3 lymph node involvement, extrapancreatic nerve plexus invasion, and stage IV disease had significantly poorer prognoses than patients without these characteristics. Conclusions  Our combined therapy for patients with PC contributed to local control; however, it provided no survival benefit, because of liver metastases.     

Results of a pancreatectomy with a limited venous resection for pancreatic cancer

PURPOSE: The indications for a pancreatectomy with a partial resection of the portal or superior mesenteric vein for pancreatic cancer, when the vein is involved by the tumor, remain controversial. It can be assumed that when such involvement is not extensive, resection of the tumor and the involved venous segment, followed by venous reconstruction will extend the potential benefits of this resection to a larger number of patients. The further hypothesis of this study is that whenever involvement of the vein by the tumor does not exceed 2 cm in length, this involvement is more likely due to the location of the tumor being close to the vein rather than because of its aggressive biological behavior. Consequently, in these instances a pancreatectomy with a resection of the involved segment of portal or superior mesenteric vein for pancreatic cancer is indicated, as it will yield results that are superposable to those of a pancreatectomy for cancer without vascular involvement. METHODS: Twenty-nine patients with carcinoma of the pancreas involving the portal or superior mesenteric vein over a length of 2 cm or less underwent a macroscopically curative resection of the pancreas en bloc with the involved segment of the vein. The venous reconstruction procedures included a tangential resection/lateral suture in 15 cases, a resection/end-to-end anastomosis in 11, and a resection/patch closure in 3. RESULTS: Postoperative mortality was 3.4%; morbidity was 21%. Local recurrence was 14%. Cumulative (standard error) survival rate was 17% (9%) at 3 years. CONCLUSION: A pancreatectomy combined with a resection of the portal or superior mesenteric vein for cancer with venous involvement not exceeding 2 cm is indicated in order to extend the potential benefits of a curative resection.     

Prophylactic breast irradiation reduces background parenchymal enhancement (BPE) on MRI: A secondary analysis

PurposeWe recently showed that prophylactic breast irradiation (PBI) reduces the risk of contralateral breast cancer in BRCA mutation carriers undergoing treatment for early breast cancer. It has been suggested that Background Parenchymal Enhancement (BPE) may be a biomarker for increased risk of breast cancer.MethodsFor participants in the trial we reviewed the MRI prior to enrollment and following radiation treatment and scored the contralateral breast for BPE and density.ResultsSignificant reduction of BPE was more commonly noted following PBI (p = 0.011) compared to the control group.ConclusionReduction of BPE by PBI may contribute to its prophylactic effect.     

联合血管切除重建的胰腺癌根治性手术

Most of the pancreatic cancer was diagnosed at advanced stages and the resection rate was only 10％-20％.Vascular invasion was a common event in the pathogenesis of pancreatic cancer.However,in the tradi...     

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.     

Surgical treatment of periampullary and pancreatic cancer

Summary   Background: Pancreatic cancer is a common malignancy in the United States with approximately 28,000 cases per year. Two-thirds of these patients will have adenocarcinoma of the pancreas, and for the majority of patients it is a lethal disease. Methods: Current diagnosis and results of surgical and adjuvant treatment options for pancreatic cancer are discussed. Results: Operative mortality has been reduced to <5% in all major centers, and direct correlation of volume with outcome has become established. Preoperative biopsy is not mandatory in our hands. Preoperative biliary drainage has not been shown to be beneficial. Prospective randomized trials of nutritional support following pancreatic resection have shown routine nutritional support to be of no value. Adjuvant treatment trials have shown limited if any benefit following resection for adenocarcinoma of the pancreas. Conclusion: Surgical resection offers the only hope for cure or significant palliation and ensures that patients with more favorable histopathologies are not neglected. Recent advances involve improvement in noninvasive diagnosis and the accurate prediction of resectability so that patients do not undergo unnecessary procedures. Current approaches focus on innovative investigative treatment regimes.      

Treatment strategy for synchronous metastases of colorectal cancer: is hepatic resection after an observation interval appropriate?

Background In cases of synchronous colorectal hepatic metastases, the primary colorectal cancer strongly influences on the metastases. Our treatment policy has been to conduct hepatic resection for the metastases at an interval of 3 months after colorectal resection. We examined the appropriateness of interval hepatic resection for synchronous hepatic metastasis. Materials and methods The subjects were 164 patients who underwent resection of hepatic metastasis of colorectal cancer (synchronous, 70 patients; metachronous, 94 patients). Background factors for hepatic metastasis and postoperative results were compared for synchronous and metachronous cases. Results The cumulative survival rate for 164 patients at 3, 5, and 10 years postoperatively was 71.9%, 51.8%, and 36.6%, and the post-resection recurrence rate in remnant livers was 26.8%. Interval resection for synchronous hepatic metastases was conducted in 49 cases after a mean interval of 131 days. No difference was seen in postoperative outcome between synchronous and metachronous cases. Conclusion The outcome was similarly favorable in cases of synchronous hepatic metastasis and in cases of metachronous metastasis. Delaying resection allows accurate understanding of the number and location of hepatic metastases, and is beneficial in determining candidates for surgery and in selecting surgical procedure.