PC is a dismal disease associated with a very poor prognosis especially for late stages, despite multimodal therapy. In the current study, we treated local advanced and metastatic PC by a Nd:YAG laser-beam fiber ablation and found good local response of the malignancies at the median 10.4 -month follow-up. LA is a novel technique to manage PC. In 2010, the first LA of pancreas study on 8 healthy pigs was performed by means of endoscopic US guidance. Currently there are four clinical case report papers that reported the initial results of the method with the enrolled patient number of 1, 1, 3 and 9. They all showed the technique was safe and useful for unresectable or recurrent PC patients under endoscopic US or per-oral pancreatoscopy guidance. For the study with 9 patients by Di Matteo FM, the median lesion size was 35.4 mm (range 21–45 mm). The patients were performed endoscopic US guided LA with the median OS of 7.4 months. To the best of our knowledge, this is the first report in the treatment of PC patients by percutaneous LA.
The American Joint Committee on Cancer (AJCC) staging system is the most widely used system to stage pancreatic cancer, which provides the basis for evaluating the resectability of the cancer and stratifying survival by stage. The unresectable categories include the subset of stage III that is defined as locally advanced and Stage IV as metastatic PC. According to the National Comprehensive Cancer Network guideline, the recommended treatment for unresectable PC were chemotherapy or chemoradiotherapy. Ablation technique was not recommended in the NCCN guideline for PC treatment, though it has achieved a vital role in the management of several malignancies such as hepatocellular carcinoma, hepatic metastatic lesions, and renal cell carcinoma for the advantage of minimally invasion and effectiveness. PC therapy is an arduous challenge for thermal ablation from anatomical consideration. Only limited studies have reported the application of ablation in experimental and clinical setting in the management of solid and cystic PC, including radiofrequency, microwave, ethanol ablation, high-intensity focused US, cryoablation and irreversible electroporation technique [5, 6, 9, 23–26]. Among them, radiofrequency, cryoablation and ethanol ablation were most commonly used methods for unresectable PC .
LA as one of the thermal therapies, it induces tumor cellular necrosis due to a localized high temperature increase by the absorption of laser energy within the tissue. Theoretically, LA shares some advantages for PC therapy. PC is physically diffuse and extends retroperitoneally. It can be traversed by the pancreatic duct and is closely related to the distal common bile duct, duodenum, stomach, transverse colon and abdominal blood vessels. The major difficulty of PC ablation in the risks of inadvertent thermal injury for adjacent tissues and almost impossibility of complete ablation of all tumor bulk. Laser can create accurate, predictable, and reproducible ablation zones that induce minimal changes outside the targeted ablation zone[10, 27]. It uses a 21-Gauge guidance needle as the ethanol ablation, which avoids the larger diameter of the radiofrequency or cryoablation needle puncture and reduces potential injury to gastrointestinal tract. And different from ethanol ablation that produces liquid distribution non-uniformly in the tumor and the limited ablation area, LA can induce a form of controlled, well-defined ablation area by fine optical fibers. These characteristics may offer potential advantages over other ablative techniques for PC treatment.
Majority of literatures reported the guidance approach of PC ablation were intra-operation and endosonography, which allowed a safer approach to target pancreatic lesions that located at deep retroperitoneal cavity. It is extremely difficult to reach PC clearly by a percutaneous approach by obtaining real-time imaging. In the current study, we tried to use US to percutaneously guide the insertion of Nd: YAG laser fibers. Results verified that percutaneous ablation under US guidance is possible to choose a safe route, and real-time US imaging can track the needle and thermal field. No significant puncture and ablation-related major complications occurred. Moreover, CEUS was used to evaluate ablation effect immediately and decisions on whether additional LA is required can be made immediately. This provided a potential of more minimal invasive technique for PC therapy.
We sum up our initial experience of percutaneous LA of PC as follows. (1) We choose lesions at body and tail of pancreas as indication in this pilot study. Such tumors had less encasement of abdominal blood vessel and were far from bile duct and duodenum, which may be safer for percutaneous ablation. (2) Gastrointestinal tract shielding is a major difficulty for percutaneous ablation. Therefore, we cleaned the intestines by using laxative at the night before LA and performed local anesthesia to relieve flatulence induced by sedation anesthesia. That may provide a clear puncture route on US imaging. (3) According to reported results of ablation of PC in recent 5 years, the ablation related mortality was 0-3% and morbidity was 3.5-28%. All of our patients achieved safe therapies without any major complication even if by percutaneous approach, which may be attribute to careful indication selection, precise US guidance and fiber placement. (4) For patients with locally advanced and metastatic PC, the median survival in most historical studies ranges from 8-12 and 5-7 months, respectively. Our study showed comparable results, but the patients shared a relatively good performance status and quality of life from LA, which avoid the ethanol ablation of celiac plexus to control pain.
Our study had several limitations. First, our population size was small, which was compatible with a pilot study. Second, we only selected tumors at body and tail of pancreas as indication. Future plans will enroll the tumors at head of pancreas. Third, we used the 3D visualization software only to calculate the ablation volume ratio and observe residual tumor stereoscopically. The technique can also be applied in planning and navigating of LA to achieve better PC therapy results in the future. A larger trial is planned to more rigorously investigate cancer-related outcomes.