Self-expanding metal stents (SEMS) provide superior outcomes compared to plastic stents for pancreatic cancer patients undergoing neoadjuvant therapy

Background

Neoadjuvant therapy is increasingly utilized for pancreatic cancer patients to decrease tumor burden in anticipation of later surgical resection. However, infectious complications such as life threatening cholangitis may occur for those with biliary obstruction. We hypothesized that placement of metal rather than plastic stents in such patients results in lower rates of stent-related complications, leading to improved clinical outcomes.

Methods

Retrospective cohort of pancreatic cancer patients treated by the University of Michigan Multidisciplinary Pancreatic Cancer Destination Program between January 2005 and June 2010. Only patients undergoing neoadjuvant therapy with one or more biliary stents placed for malignant obstruction were studied. Time to stent complication was compared between metal and plastic stents. The complication rate was estimated as the ratio of complications to total stent exposure time and 95% confidence intervals were calculated.

Results

52 patients met inclusion criteria. A total of 113 stents were placed in 52 patients (70 plastic, 43 metal). The complication rate was almost 7 times higher with plastic stents, 0.20 (95% CI, 0.14-0.30), than with metal stents, 0.03 (95% CI, 0.01-0.06). Moreover, the rate of hospitalization for stent-related complications was 3-fold higher in the plastic stent group than the metal stent group. The first quartile estimate of time to stent complication was almost 5 times longer for metal than for plastic stents (44 vs. 200 days) (P<0.0001).

Conclusion

Compelling evidence indicates that self-expanding metal, not plastic stents should be used for malignant biliary obstruction in patients undergoing neoadjuvant therapy for pancreatic cancer.Key Words: Pancreatic cancer, jaundice, chemotherapy, bile duct stents     

Preoperative chemoradiation for patients with pancreatic cancer: toxicity of endobiliary stents.

PURPOSE: A recent multicenter study of preoperative chemoradiation and pancreaticoduodenectomy for localized pancreatic adenocarcinoma suggested that biliary stent-related complications are frequent and severe and may prevent the delivery of all components of multimodality therapy in many patients. The present study was designed to evaluate the rates of hepatic toxicity and biliary stent-related complications and to evaluate the impact of this morbidity on the delivery of preoperative chemoradiation for pancreatic cancer at a tertiary care cancer center. PATIENTS AND METHODS: Preoperative chemoradiation was used in 154 patients with resectable pancreatic adenocarcinoma (142 patients, 92%) or other periampullary tumors (12 patients, 8%). Patients were treated with preoperative fluorouracil (115 patients), paclitaxel (37 patients), or gemcitabine (two patients) plus concurrent rapid-fractionation (30 Gy; 123 patients) or standard-fractionation (50.4 Gy; 31 patients) radiation therapy. The incidences of hepatic toxicity and biliary stent-related complications were evaluated during chemoradiation and the immediate 3- to 4-week postchemoradiation preoperative period. RESULTS: Nonoperative biliary decompression was performed in 101 (66%) of 154 patients (endobiliary stent placement in 77 patients and percutaneous transhepatic catheter placement in 24 patients). Stent-related complications (occlusion or migration) occurred in 15 patients. Inpatient hospitalization for antibiotics and stent exchange was necessary in seven of 15 patients (median hospital stay, 3 days). No patient experienced uncontrolled biliary sepsis, hepatic abscess, or stent-related death. CONCLUSION: Preoperative chemoradiation for pancreatic cancer is associated with low rates of hepatic toxicity and biliary stent-related complications. The need for biliary decompression is not a clinically significant concern in the delivery of preoperative therapy to patients with localized pancreatic cancer.     

Malignant biliary obstruction: From palliation to treatment

Malignant obstruction of the bile duct from cholangiocarcinoma, pancreatic adenocarcinoma, or other tumors is a common problem which may cause debilitating symptoms and increase the risk of subsequent surgery. The optimal treatment - including the decision whether to treat prior to resection - depends on the type of malignancy, as well as the stage of disease. Preoperative biliary drainage is generally discouraged due to the risk of infectious complications, though some situations may benefit. Patients who require neoadjuvant therapy will require decompression for the prolonged period until attempted surgical cure. For pancreatic cancer patients, self-expanding metallic stents are superior to plastic stents for achieving lasting decompression without stent occlusion. For cholangiocarcinoma patients, treatment with percutaneous methods or nasobiliary drainage may be superior to endoscopic stent placement, with less risk of infectious complications or failure. For patients of either malignancy who have advanced disease with palliative goals only, the choice of stent for endoscopic decompression depends on estimated survival, with plastic stents favored for survival of < 4 mo. New endoscopic techniques may actually extend stent patency and patient survival for these patients by achieving local control of the obstructing tumor. Both photodynamic therapy and radiofrequency ablation may play a role in extending survival of patients with malignant biliary obstruction.     

胆管支架治疗恶性梗阻性黄疸５３例分析

目的　观察经皮肝穿刺肝胆管支架治疗恶性梗阻性黄疸的疗效及不良反应。方法　５３例恶性胆道梗阻患者采用经皮肝穿刺置入胆管支架治疗,术前及术后１周复查血清总胆红素、直接胆红素。２２例患者行肝动脉栓塞化疗（ＴＡＣＥ）。结果　共置入５５枚镍钛形状记忆合金内支架,其中２例各置入２枚胆道支架,技术操作成功率１００％。术前及术后１周血清总胆红素、直接胆红素均有显著差异（Ｐ＝０.０２１,Ｐ＝０.０１８）,支架置入后行ＴＡＣＥ者中位生存期（３９.２周）明显高于未行ＴＡＣＥ组（１７.３周）,术中及术后的并发症经及时处理后均能缓解。结论　对梗阻性黄疸患者经皮肝穿刺支架治疗对解除胆道梗阻是一种安全、有效的方法。术后行肝动脉栓塞化疗者能明显延长患者生存。     

经皮肝穿胆道支架置入治疗恶性胆道梗阻的临床研究

目的：总结经皮肝穿刺胆道金属内支架植入治疗恶性胆道梗阻的临床疗效及经验。方法：92例恶性胆道梗阻性黄疸患者,采用经皮肝穿刺肝胆管支架置入术。根据胆道梗阻狭窄的不同部位和狭窄的程度采用相应的放置方式。结果：92例患者中,91例胆道支架成功放置,其中12例放置双支架,支架扩张良好,引流通畅,血清胆红素下降明显。术后死亡2例,胆道出血3例,腹水渗漏6例,胆漏2例,支架移位1例,胆管炎9例,胆道再阻塞11例。结论对不能手术的恶性胆道梗阻性黄疸患者,经皮肝穿刺胆道内支架植入术创伤小,可提高患者的生存质量,延长生存期,是一种较为安全、有效的方法。     

Percutaneous transhepatic hybrid biliary endoprostheses using both plastic and metallic stents for palliative treatment of malignant common bile duct obstruction

To evaluate clinical safety and efficacy of percutaneous transhepatic hybrid biliary prostheses for palliative treatment in patients with common bile duct obstruction caused by advanced malignancies. A total of 13 consecutive patients was treated with percutaneous transhepatic biliary endoprostheses concurrently using both plastic and metallic stents. Serum total bilirubin levels before and after stent placement were evaluated. The technical success rate, the period with no obstructive jaundice, patient survival and complications were also assessed. Median bilirubin levels decreased from 3.8 mg/dL before to 1.2 mg/dL after stent placement, and this difference was statistically significant. The median no‐jaundice period after bile duct stent placement was 6.0 months (range: 2–11 months), and overall survival time was 7.0 months. Of the 13 patients, nine did not have recurrent jaundice by the time of death, whereas four (31%) had recurrent jaundice. A second intervention was performed in these four patients. A new plastic stent was placed and jaundice did not recur up to the time of death. No serious complications such as cholangitis, pancreatitis or bile duct perforation developed. Percutaneous transhepatic hybrid biliary endoprostheses using both plastic and metallic stents can be useful as non‐invasive palliative treatment to relieve jaundice in patients with malignant obstructive jaundice.     

Endoscopic stent for palliating malignant and benign biliary obstruction

Objective: To study the techniques of placement of memory alloy plating gold biliary stent and plastic stent for palliation of malignant and benign biliary obstruction, and to assess its clinical effectiveness. Methods: The patients in plastic stent group included papliila of duodenum inflamational strictures (n=24), common bile duct inflammational inferior segment strictures (n=4),choledocholithiasis (n=5), bile leak (n=11), bile duct surgery injurey (n=7) and pancreatic carcinoma (n=1).The patients in plating gold stent group included common bile duct carcinoma (n=5) and pancreatic carcinoma (n=6). Under fluoroscopic guidance the stent was inserted into biliary obstruction sites from oral cavity in all cases. Complications, liver function and blood serum amylase were investigated during the study period. Results: Successful stent placement was achieved in all cases. After operation of 7 days, in gold biliary stent groups, the rates of decrease of blood serum total bilirubin, glutamic-pyruvic transaminase, r-glutamyl transpeptidase and alkaline phosphatase were 67.16%,58.37%, 40.63% and 41.54% respectively. In plastic stent group, the rates of decrease of STB, ALT, r-GT and AKP were 53.24%, 55.03%, 37.15%, 34.12% respectively.Early complication included post-ERCP panereatitis and eholangititis. Occlusion of stent was the major late complication. Conclusion: Memory alloy plating gold biliary stent and plastic stent were safe and efficacious methods for malignant and benign biliary obstruction, and could improve patient‘s living quality. Plastic stent was an efficient complement for therapy of bile leak and bile duct injury.     

Self-expandable metallic stents for patients with recurrent esophageal carcinoma after failure of primary chemoradiotherapy.

BACKGROUND: Recent advances in chemoradiotherapy for esophageal carcinoma have resulted in improved survival rates. However, there are few options for recurrent dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy. The aim of this study was to evaluate the safety and efficacy of self-expandable metallic stent placement for patients with recurrent esophageal carcinoma where definitive chemoradiotherapy has failed. METHODS: Thirteen consecutive patients with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable metallic stents were placed after failure of primary chemoradiotherapy, were studied retrospectively. All patients had esophageal obstruction or malignant fistula. RESULTS: The oral alimentation status of nine of 13 patients (69%) improved after successful placement of the stent. Following placement of the stent, fever (>38 degrees C) and severe chest pain occurred in 85% (11/13) of the patients. In all patients examined, C-reactive protein was elevated within 1 week of the operation. Esophageal perforation occurred in three patients. Stent-related mediastinitis and pneumonia developed in six (46%) and three (23%) patients, respectively. Seven of the 13 patients (54%) died of stent-related pulmonary complications. CONCLUSION: Although the placement of a self-expandable metallic stent for patients with recurrent esophageal carcinoma after failure of chemoradiotherapy improved their oral alimentation status, we found that this treatment increases the risk of life-threatening pulmonary complications.     

支架置入术治疗恶性低位胆道梗阻的临床价值

目的 探讨金属胆道支架置入术治疗恶性低位胆道梗阻的有效性、安全性.方法 32例恶性胆道低位梗阻患者(中位年龄61岁),术前经CT和磁共振胰胆管造影(magnetic resonance cholangiopancreatography,MRCP)证实为恶性胆道低位梗阻.其中,胆管癌12例,胰头癌11例,壶腹癌5例,转移癌2例,胆囊癌2例.32例患者行经皮经肝胆道穿刺,于胆总管中下端置入32枚自膨式金属胆道支架.结果 32例患者手术成功率100.0％,支架位置良好,胆汁引流通畅.术中无胆道出血、胆汁渗漏及胆道破裂等严重并发症.32例患者于术后7天复查肝功能,其血清总胆红素(total bilirubin,TB)由术前的(378.11±134.53) μmol/L下降至(166.10 ±74.37) μmol/L(P＜0.05);血清直接胆红素(direct bilirubin,DB)由术前的(219.14±86.37) μmol/L下降至(98.26 ±53.68) μmol/L(P＜0.05).29例于术后30天复查肝功能,其血清TB由术前的(356.78±118.21) μmol/L下降至(56.10±44.37)μmol/L;血清DB由术前的(219.14 ±86.37) μmol/L下降至(38.26±43.68) μmol/L,均P＜0.05.30例获得随访,随访1-42月(平均25.4月),9例再发支架内梗阻(30.0％),其中4例再行支架治疗,3例行导管引流治疗,2例未治疗死亡.十二指肠梗阻1例,行十二指肠支架治疗后缓解.生存期1-33月,平均生存期(11.56±2.14)月,中位生存期10.0月.结论 金属胆道支架置入术是治疗恶性低位胆道梗阻的安全、有效的方法.     

Endoscopic treatment options for cholangiocarcinomas

Cholangiocellular carcinoma (CCC) is a very aggressive tumor, which remains highly resistant to current chemoradiation therapies. Death is usually caused by the tumor burden. However, biliary obstruction, which leads to cholangitis and liver failure, is also a cause of death. Therefore, relief of biliary obstruction is one of the key palliative treatment options for patients with hilar or distal CCC. Radiologic or endoscopic insertions of stents (plastic or self-expanding metal) are definite biliary drainage options. Whereas stents alone can help achieve relief of bile duct obstruction, endoscopic ablative interventions with photodynamic therapy or radiofrequency ablation are also useful in destroying intraluminal tumor. Destroying the tumor leads to an increase in the luminal diameter of the obstructed bile duct, allowing for placement of more or larger diameter stents, and thus improving bile flow. Besides decreasing morbidity associated with obstruction, ablative therapies such as photodynamic therapy have also been associated with improved survival in a sub-group of patients with CCC and should therefore be incorporated into the treatment algorithm of any center treating patients with CCC.     

Palliative Therapie des fortgeschrittenen Pankreaskarzinoms

In spite of advances in the management of other malignancies, the prognosis of patients with advanced pancreatic cancer remains poor. Palliative therapy is an essential element of the treatment strategy. In this review we discuss important areas of the palliative therapy of advanced pancreatic cancer. We focus on complications of pancreatic cancer, such as stenosis of the common bile duct, duodenal obstruction and thrombosis as well as on supportive therapy. The endoscopic implantation of self-expanding metal stents is a safe procedure with a high success rate to obtain adequate biliary drainage. In cases of malignant duodenal obstruction palliation is also mainly achieved by endoscopic stenting. A main area of supportive care is an appropriate pain treatment, following the WHO scheme for pain therapy. Weight loss in patients with pancreatic cancer is often due to pancreatic exocrine insufficiency, which is treated by supplementation of pancreatic enzymes.     

胰腺癌患者行内镜逆行胰胆管造影术放置胰管支架后发生胰腺炎的危险因素分析

目的:确定胰腺癌患者行内镜逆行胰胆管造影术放置胰管支架后发生胰腺炎的危险因素。方法:收集2016年4月至2018年7月62名初次接受内镜逆行胰胆管造影术,并在术中插入了胰腺支架预防术后急性胰腺炎的胰腺癌患者的资料。其中术后发生急性胰腺炎患者24例,未发生胰腺炎患者38例,采用固定回归和随机效应的Logistic回归模型对ERCP术放置胰管支架后发生胰腺炎患者进行建模。结果:Logistic回归显示年轻、女性、高血压、插管时间超过60 min、胰管支架放置于胰头、插管次数为ERCP术放置胰管支架后发生胰腺炎的危险因素。高血压、插管时间超过60 min、胰管支架放置于胰头为其独立危险因素。结论:高血压,插管时间过长和胰管支架放置在胰头部位,决定了胰腺癌患者行内镜逆行胰胆管造影术放置胰管支架后更容易发生胰腺炎。     

胆管支架和(或)引流术治疗恶性胆管梗阻30天内死亡原因分析

目的 分析胆管支架和（或）引流术治疗恶性胆管梗阻３０ｄ内死亡原因及手术有关的近期并发症,探讨更有效的临床治疗方法及手术适应证。方法 １０７例恶性胆管梗阻者实行经皮经肝穿刺担管支架和（或）引流术,术后３０ｄ内共死亡１２例,其中原发性肝癌４例,肝门淋巴结转移瘤３例,胆管癌５例,死亡率为１１．２％。结果 １２例恶性胆管梗阻者,９例放置胆管支架,其中５例同时置引流管;３例仅置胆管引流管。手术后１０例胆管梗     

Cost Effectiveness of Metal Stents in Relieving Obstructive Jaundice in Patients with Pancreatic Cancer

Background

ASGE and ESGE guidelines recommend endoscopic metal stent placement for pancreatic carcinoma patients with biliary obstruction, and whose estimated life expectancy is greater than 6 months. Because median overall survival (OS) of metastatic pancreatic adenocarcinoma until recently has been less than 6 months, plastic biliary stents were preferentially placed rather than metal due to the greater upfront cost of the latter. Recent advances in the treatment of metastatic pancreatic cancer have extended median OS beyond the 6-month range. Given this improvement in OS, we performed a cost-effectiveness analysis of initial metal biliary versus plastic stent placement in metastatic pancreatic cancer patients with biliary obstruction.

Methods

A Markov model was developed to predict lifetime costs, quality-adjusted life years (QALYs), and cost effectiveness of metal compared with plastic stents. Adult patients entered the model with locally advanced cancer and underwent endoscopic retrograde cholangiopancreatography (ERCP) with placement of metal or plastic stents. A targeted literature search was conducted to identify published sources, which were used to estimate clinical, cost, utility, and event rate inputs to the model. Results were estimated from the third-party payer perspective in 2012 US dollars per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the impact on model outcomes resulting from uncertainty among inputs.

Results

Our analysis found that initial placement of metal stents was more cost effective than plastic biliary stents with lower overall costs due to lower restenting rates while at the same time associated with a better quality of life. Based on model projections, placement of metal stents could save approximately $1450 per patient over a lifetime, while simultaneously improving quality of life. These findings were robust in sensitivity analyses.

Conclusions

Placement of metal biliary stents at initial onset of obstructive jaundice in adult patients with metastatic pancreatic carcinoma with an expected OS greater than 6 months was found to be a more cost-effective strategy than plastic stents. These results reinforce guidelines’ suggestions for metal stent placement.

     

Role of self expandable stents in management of colorectal cancers

Acute malignant colorectal obstruction is a complication of colorectal cancer that can occur in 7%-29% of patients. Self-expanding metallic stent placement for malignant colorectal obstruction has gained popularity as a safe and effective procedure for relieving obstruction. This technique can be used in the palliation of malignant colorectal obstruction, as a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn’s disease, radiation therapy, and diverticular diseases. Self-expanding metallic stent has its own advantages and disadvantages over the surgery in these indications. During the insertion of the self-expanding metallic stent, and in the follow-up, short term and long term morbidities should be kept in mind. The most important complications of the stents are perforation, stent obstruction, stent migration, and bleeding. Additionally, given the high risk of perforation, if a patient is treated or being considered fortreatmentwith antiangiogenic agents such as bevacizumab, it is not recommended to use self-expanding metallic stent as a palliative treatment for obstruction. Therefore, there is a need for careful clinical evaluation for each patient who is a candidate for this procedure. The purpose of this review was to evaluate self-expanding metallic stent in the management of the obstruction of the colon due to the colorectal and extracolonic obstruction.     

Palliation of malignant bile duct obstruction with metallic stent-clinical effectiveness in aged patients

To evaluate the clinical effectiveness of metallic stent in the palliation of malignant bile duct obstruction in aged patients, 30 patients over 65 years of age with malignant biliary obstruction were investigated retrospectively. Overall survival duration after the stent placement was 13-1,275 (mean: 278, median: 169) days. The period of tube-free on the outpatient basis after stent insertion was 0-1,162 (mean: 192, median: 121) days. The estimated cost savings by eliminating hospitalization was greater than the stent cost. Four patients survived over 18 months despite their advanced clinical stages. It seems difficult to develop guidelines for the indication of stent placement in the treatment of malignant bile duct obstruction for aged patients.     

The best choice of biliary stents in hilar distal strictures due to inoperable malignacies

Recently, the treatment using biliary stents play an important role to improve the quality of life (QOL) in patients with inoperable malignant biliary obstruction. Long-term patency is preferable, but the convenience of treatment for stent obstruction should also be considered. In this study, we investigated which stent is currently the most appropriate in hilar and extrahepatic bile duct obstruction. In hilar obstruction, metallic stents (MS) had significantly longer patency than plastic tube stents (TS). As for extrahepatic bile duct obstruction, covered MS (CMS) and MS had significantly longer patency than TS. On the other hand, many difficulties occurred when the MS was obstructed. In some of these patients, it was difficult to place the internal drainage again and their QOL was severely impaired. CMS was more convenient because it could be removed when it was obstructed. These results may suggest that MS should be used carefully in the hilar obstruction and that CMS is the best for the treatment of extrahepatic bile duct obstruction.     

经内镜植入自膨式金属支架治疗结直肠癌性梗阻的安全性与有效性分析

目的探讨经内镜植入自膨式金属支架治疗结直肠癌性梗阻的安全性与有效性。方法选择收治的结直肠癌性梗阻患者48例,根据治疗方法的不同分为对照组22例与治疗组22例,对照组给予常规经内镜鼻胆管引流术治疗,治疗组给予经内镜植入自膨式金属支架治疗。结果所有患者都一次性完成手术,两组术后14天的总胆红素与直接胆红素含量都明显低于术前(P<0.05),同时术后14天治疗组的总胆红素与直接胆红素含量明显低于对照组(P<0.05)。治疗组术后14天内的急性胰腺炎、出血、胆漏、穿孔等并发症发生情况明显少于对照组(P<0.05)。所有患者术后随访6个月,治疗组随访3个月与6个月的生存率分别为100.0%和95.8%,对照组分别为83.3%和75.0%,治疗组随访3个月与6个月的生存率明显高于对照组(P<0.05)。结论经内镜植入自膨式金属支架治疗结直肠癌性梗阻的手术成功率高,能有效发挥减黄效果,减少术后并发症的发生,从而延长患者的生存时间。     

Radiotherapy with multiple fractions per day in pancreatic and bile duct cancer

Twenty patients with pancreatic and bile duct cancer have been treated with external radiotherapy with multiple fractions per day (MFD). All patients had localized disease only. Sixteen patients have been treated with a split-course technique, to a dose of 60 to 70 Gy in 7-8 weeks, four patients had a continuous series of 44 Gy in 19 days. The mean survival was 7.9 months for patients with a pancreatic cancer. Four out of nine patients with pancreatic cancer in whom the tumour was evaluable showed a tumour regression, one out of nine reached a partial remission. The mean survival in the responders was 9.5 months. All patients with pancreatic cancer died of their tumour. Four out of eight patients with bile duct cancer died of their tumour, the mean survival was 10 months. Four patients with bile duct cancer are still alive (10+, 10+, 10+, 11+ months). No serious acute toxicity was seen. Six patients showed gastrointestinal toxicity at 1.5 to 9 months after the end of treatment. All of them could be treated in a conservative way. From the results obtained in this feasibility study, radiotherapy with MFD in pancreatic and bile duct cancer appears to achieve similar tumour response as conventionally fractionated radiotherapy and the observed toxicity of MFD can be considered as acceptable. MFD might be a more appropriate treatment scheme for combination with chemotherapy and radiosensitizers.     

Palliative percutaneous drainage in malignant biliary obstruction. Part 1: indications and preprocedure evaluation

A diagnosis of liver metastasis, periportal adenopathy, or hepatobiliary cancer often is accompanied by findings of biliary obstruction. Malignant biliary obstruction frequently is associated with pruritus, anorexia, cholangitis, or hyperbilirubinemia, which that precludes treatment with chemotherapeutic agents that are excreted or metabolized hepatically. In patients with low biliary obstruction, endoscopic stent placement may accomplish drainage of the entire biliary tree without the need for an external device. Patients with high bile duct obstruction, on the other hand, may need a percutaneous approach to drain the target ducts and avoid draining an atrophic segment or lobe.This first of a series of two articles concerning palliative percutaneous biliary intervention will review the indications for biliary drainage and the preprocedure evaluation of this complicated patient population.