Radiofrequency ablation of locally advanced pancreatic adenocarcinoma: An overview

Radiofrequency ablation(RFA)of pancreatic neoplasms is restricted to locally advanced,non-resectable but nonmetastatic tumors.RFA of pancreatic tumors is nowadays an ultrasound-guided procedure performed during laparotomy in open surgery.Intraoperative ultrasound covers the mandatory role of staging,evaluation of feasibility,guidance and monitoring of the procedure.Different types of needle can be used.The first aim in the evaluation of RFA as a treatment for locally advanced pancreatic ductal adenocarcinom...     

Radiofrequency ablation in pancreatic cancer

Introduction and aim. Radiofrequency ablation (RFA) is effective in the treatment of unresectable hepatic tumors and promising results have also been described in tumors of kidney, lung, brain, prostate, and breast. The radiofrequency destruction of solid pancreatic tumors sounds logical but also seems risky due to the friable pancreatic parenchyma, the fear of pancreatitis and the prejudiced myth of ‘the pancreas is not your friend’. Patients and methods. We present our initial experience and we describe our technique during intraoperative RFA in four patients with locally advanced and unresectable pancreatic adenocarcinoma (head of pancreas, three; body-tail, one; diameter, 3–12 cm). In all the patients, the RFA was followed by bypass palliative procedures (cholecystojejunostomy and Brown''s anastomosis and/or gastrojejunostomy). A drainage tube was left close to the ablated area. Serum amylase and fluid amylase (drain) were measured for 5–7 days postoperatively. Sandostatin was also administered prophylactically for 3–5 days. Results. The postoperative period was uneventful in all the patients, without complications or evidence of pancreatitis. The post RFA CT scan showed remarkable changes in the density and the characteristics of the tumors in all the patients. All the patients are alive, at 12, 8, 5 and 3 months postoperatively, respectively. In one patient (with cancer of the body of the pancreas) who was receiving morphine because of intolerable pain, significant pain relief has been observed. Conclusions. From our initial results, RFA seems to be a feasible, potentially safe and promising option in patients with locally advanced and unresectable pancreatic cancer. Nevertheless, larger series of cases are needed to secure our encouraging results.     

放疗联合化疗治疗不可手术局部晚期非小细胞肺癌

目的 比较长春瑞宾／顺铂（NP方案）联合同步放疗对局部晚期非小细胞肺癌（NSCLC）的疗效与安全性。方法　60例ⅢA或ⅢB期NSCLC患者接受NP＋同步放化疗（同步组）或MVP／VP方案＋序贯放疗（序贯组）。放疗剂量范围在40～66Gy。结果　序贯组有效率为33％，明显低于同步组的63％；两组中位生存期相似。同步组47％患者出现不同程度的放射性食管炎症状，明显高于序贯组的13％；Ⅲ／Ⅳ食管炎在同步组为20％。结论　低剂量NP方案化疗联合同步胸部放射一线治疗局部晚期NSCLC有效，患者可以耐受。     

The role of irreversible electroporation (IRE) for locally advanced pancreatic cancer: a systematic review of safety and efficacy

Objectives: Irreversible electroporation (IRE) is a new modality for tumor ablation. Electrodes are placed around the tumor, and a pulsed, direct current with a field strength of 2000 V/cm is delivered. The direct current drives cells into apoptosis and cell death without causing significant heating of the tissues, which spares the extracellular matrix and proteins. The purpose of this review was to evaluate current experience of IRE for the ablation of pancreatic cancer.

Material and methods: We searched PubMed for all studies of IRE in human pancreatic cancer in English reporting at least 10 patients.

Results: The search yielded 10 studies, comprising a total of 446 patients. Percutaneous IRE was done in 142 patients, while 304 patients were treated during laparotomy. Tumor sizes ranged from median 2.8 to 4.5?cm. Post-procedural complications occurred in 35% of patients, most of them were less severe. Nine patients (2.0%) died after the procedure. The technical success rate was 85–100%. The median recurrence-free survival was 2.7–12.4 months after IRE treatment. The median overall survival was 7–23 months postoperatively. The longest overall survival was noted when IRE was used in conjunction with pancreatic resection.

Conclusions: IRE seems feasible and safe with a low post-procedural mortality. Further efforts are needed to address patient selection and efficacy of IRE, as well as the use of IRE for ‘margin accentuation’ during surgical resection.     

Paclitaxel as a radiation sensitizer for locally advanced pancreatic cancer

Paclitaxel and concurrent radiation (paclitaxel/RT) have been evaluated by the Brown University Oncology Group (BrUOG) and the Radiation Therapy Oncology Group (RTOG) in phase I and II studies for patients with locally advanced pancreatic cancer. The dose limiting toxicities were abdominal pain within the radiation field, nausea and anorexia. The phase II Brown University study, utilizing paclitaxel 50 mg/m(2) per week for 6 weeks with 50.4 Gy radiation, demonstrated modest locoregional activity and acceptable toxicity. The median and 1-year survival of paclitaxel/RT in the RTOG phase II study suggests an improvement over previous RTOG studies of fluorouracil (5-FU) and radiation. The addition of gemcitabine to paclitaxel and radiation has also demonstrated promising preliminary activity and a phase II study by the RTOG is being initiated.     

Neoadjuvant therapy for downstaging of locally advanced hilar cholangiocarcinoma: a systematic review

Background

Hilar cholangiocarcinoma is a rare but highly lethal type of cancer. A minority of patients present with resectable disease. Surgery remains the only treatment modality offering a chance of long-term survival. Unresectable patients are typically offered palliative treatment. The aim of this systematic review was to summarize the evidence for neoadjuvant therapy followed by surgical resection in patients presenting with hilar cholangiocarcinoma.

Methods

Cochrane databases, Medline, PubMed and EMBASE were systematically searched to identify articles describing neoadjuvant therapy and surgical resection or re-assessment of resectability in patients with hilar cholangiocarcinoma. Included were all articles with original research. Study selection and data extraction were performed separately by two reviewers using a standardized protocol.

Results

From 732 articles 8 full text articles and 2 abstracts met the inclusion criteria. The 2 abstracts and 1 full text article were case reports, 3 articles were retrospective and 4 were prospective studies (2 phase I and 2 phase II studies). Photodynamic therapy, chemotherapy and radiation therapy were used in various indications in populations that included patients with hilar cholangiocarcinoma, some of which were primarily unresectable. Overall quality of articles was limited.

Conclusion

Current evidence suggests that neoadjuvant therapy in patients with unresectable hilar cholangiocarcinoma can be performed safely and in a selected group of patients can lead to subsequent surgical R0 resection. Surgical resection of downstaged patients should be assessed in properly designed phase II studies.     

Intensified neoadjuvant radiochemotherapy for locally advanced rectal cancer: a review

Background The rate of local recurrence of locally advanced rectal cancer (stage III and IV according to the criteria of Union Internationale Contre Le Cancer) is still high, and also the rate of distant metastases. There are a lot of phase I/II trails of intensified neoadjuvant radiochemotherapy with different chemotherapeutic agents and current protocols to radiotherapy. Aim The objective of this review of literature was to evaluate the necessity, the results, and comparability of the different regimes and to evaluate a potential impact on later adjuvant chemotherapy.     

Microwave ablation in locally advanced pancreatic carcinoma--a new look

BACKGROUND/AIMS: Pancreatic carcinoma is by far the most common malignancy and is the 5th most lethal cancer in the world and 40% of these carcinomas are locally advanced and unresectable at the time of presentation. Palliative surgery and chemoradiotherapy have not produced significant improvement in survival. The overall prognosis of these pancreatic cancers is poor, if left untreated without any form of palliation. Out of many palliative methods adopted for such locally advanced pancreatic carcinoma, none has shown much survival benefit. Microwave ablation is a well established and safe local ablative method for liver tumors and microwave ablation for locally advanced pancreatic tumors has been extensively used around the world. This is our largest series of microwave ablation in 15 patients with locally advanced pancreatic head carcinoma. The aim of this study was to evaluate the safety, efficacy, feasibility and complications of microwave ablation in unresectable locally advanced pancreatic carcinoma. METHODOLOGY: In total, 15 patients, from January 2004 to December 2006, were included in this study all having locally advanced pancreatic tumors which were found to be unresectable on radiological evaluation. The 15 patients (10 male and 5 female) with a mean age of 67 years were subjected to open microwave ablation after laparotomy and additional palliative procedure like biliary bypass (end-to-side hepaticojejunostomy) and gastric obstruction bypass by antecolic gastrojejunostomy was performed in 6 patients. The location of tumor was predominantly in the head and/or uncinate portion of the pancreas (n=12) and head and body (n=3). The average size of tumor was 6cm (range 4-8cm) and almost all had major regional vascular invasion on CT or MR angiogram. All tumors were histologically proven before the procedure by core needle and frozen section biopsy. Patients with distant metastasis were not included in this study. RESULTS: In all 15 patients, partial necrosis was achieved. There was no major procedure-related morbidity or mortality. Minor complications were seen in 6 out of 15 patients, mild pancreatitis (2), asymptomatic hyperamylasia (2), pancreatic ascites (1), and minor bleeding (1). All patients had close follow-up and the longest surviving patient had a follow-up of 22 months. CONCLUSIONS: Microwave ablation is a beneficial therapy as a local effective procedure which is feasible and safe with acceptable minor complications in a locally advanced pancreatic tumor which can be used as part of a palliative or multimodality treatment, however, further long-term and properly designed studies are required to prove its usefulness in achieving survival benefit.     

Radiofrequency ablation of an unresectable abdominal tumor

Remnant malignant tissue is left behind after conventional surgery for an unresectable intraperitoneal malignant tumor. Standard radiotherapy or chemotherapy rarely enables good tumor control. We report the case of a 74-year-old man who developed a local recurrence of a sigmoid tumor located 5 to 6 cm from the anus. The tumor was fixed to the pelvic wall and could not be totally eradicated with conventional surgery. Preoperative peroperative assessment confirmed the absence of metastatic spread. Radiotherapy could not be performed due to risk of bowel injury. Peroperative radiofrequency ablation was followed by surgical colorectal resection without restoration of intestinal continuity, leaving only tumor tissue destroyed by radiofrequency. No adjuvant treatment was proposed because of intolerance to chemotherapy. Clinical assessment and thoracic and abdominal CT scan confirmed the absence of recurrence 26 months after radiofrequency ablation. Serum markers remained normal.     

Clinical impact of radiotherapy for locally advanced pancreatic cancer

Background

Although a randomized controlled trial for locally advanced pancreatic cancer (PC) has demonstrated a survival advantage for treatment with gemcitabine alone, chemoradiotherapy remains the treatment of choice for locally advanced disease in Japan. The aim of this study was to compare the survival benefits associated with gemcitabine and concurrent chemoradiotherapy in locally advanced unresectable PC.

Patients

Seventy-seven patients with locally advanced unresectable PC were retrospectively enrolled from April 2001 to December 2006. All cases were histologically proven, and patients received gemcitabine chemotherapy (n = 30) or concurrent chemoradiotherapy (based on 5-fluorouracil, n = 28, or gemcitabine, n = 19, as a radiosensitizer) at Aichi Cancer Center Hospital.

Results

Patients who received chemoradiotherapy had significantly better performance status than those who had chemotherapy. Tumor response was 0% for chemotherapy and 13% chemoradiotherapy, but survival benefit was similar among patients in the chemotherapy group (overall response (OS) 12 months; progression-free survival (PFS), 3 months) and those in the chemoradiotherapy group (OS, 13 months; PFS, 5 months). Two-year survival was 21% for chemotherapy patients and 19% for chemoradiotherapy patients. Severe toxicities (Grade 3–4 National Cancer Institute-Common Toxicity Criteria, version 3.0) were significantly more frequent for chemoradiotherapy than for chemotherapy.

Conclusions

Gemcitabine chemotherapy showed similar survival benefit compared to 5-fluorouracil- and gemcitabine-based chemoradiotherapy.     

Current management of locally advanced pancreatic cancer

Almost 30% of patients with pancreatic cancer present with large, locally advanced tumors in the absence of distant metastases. Because surgical resection is frequently contraindicated by vascular invasion, locally advanced pancreatic cancer has a dismal prognosis with a 6-10-month median survival. Recent advances in the multimodality treatment of other gastrointestinal malignancies have not altered the management of patients with locally advanced pancreatic cancer, a clinical dilemma reflected by the number of nonrandomized trials and anecdotal reports addressing this difficult disease. Our review summarizes the current status of aggressive surgical resection and neoadjuvant chemoradiation for locally advanced pancreatic cancer and suggests a treatment algorithm for patients with this disease based upon published clinical evidence.     

Pancreatoduodenectomy with colon resection for pancreatic cancer: a systematic review

Background

Radical resection of advanced pancreatic cancer may occasionally require a simultaneous colon resection. The risks and benefits of this combined procedure are largely unknown. This systematic review aimed to assess short and long term outcome after pancreatoduodenectomy with colon resection (PD-colon) for pancreatic ductal adenocarcinoma (PDAC).

The treatment of locally advanced pancreatic cancer: a practice guideline.

BACKGROUND: Pancreatic adenocarcinoma is the fourth most common cause of adult cancer death. About 50% of patients present with metastatic disease, 20% with resectable disease and the remaining 30% of patients are diagnosed with incurable, locally advanced unresectable but nonmetastatic pancreatic cancer. OBJECTIVES: To evaluate the current evidence regarding treatment of incurable, locally advanced, unresectable but nonmetastatic pancreatic cancer and produce an evidence-based practice guideline. METHODS: A systematic review of the literature was performed. The MEDLINE, CANCERLIT, and Cochrane Library databases were searched using the following medical subject heading search terms: 'pancreatic neoplasms', 'chemotherapy, adjuvant', 'radiotherapy', 'immunotherapy', combined with the text words: 'chemotherapy', 'radiotherapy', 'radiation', 'immunotherapy', combined with terms for the following study designs or publication types: practice guidelines, meta-analyses and randomized controlled trials. The Physician Data Query clinical trials database and the proceedings of the annual meetings of the American Society of Clinical Oncology (1996 to 2001) and the American Society for Therapeutic Radiology and Oncology (1999 to 2001) were searched for reports of new or ongoing trials. Relevant literature was selected and reviewed independently, and the reference lists from these sources were searched for additional trials. Interpretation of evidence was resolved by consensus. RESULTS: Eight randomized trials were obtained that met the inclusion criteria. CONCLUSIONS: Recommendations are to offer combined chemotherapy and radiotherapy to suitable patients. The preferred chemotherapeutic agent to combine with radiotherapy is bolus or infusional 5-fluorouracil, but the optimal mode and duration of 5-fluorouracil delivery is unclear. Chemotherapy alone with gem-citabine is an acceptable alternative.