Despite ongoing research in esophageal cancer, the overall median survival following curative esophagectomy has been shown to be 34–38.6 months [13,14] with a 7 month median survival following detection of recurrent esophageal cancer [14]. Palliation therapies are needed for both survival prolongation and symptom relief. Current palliation approaches include feeding tubes, dilation, stents, radiation, chemotherapy and various ablative techniques, all of which have benefits and risks [4,15].
The mechanism of action underlying the injury caused by CSA is unique for an ablative technique. CSA induces apoptosis and causes cryonecrosis at super-cold temperatures (-76°C to -158°C), which results in transient ischemia at the CSA site and can cause immune stimulation [16]. Some precancerous lesions such as Barrett's epithelium and many cancers are resistant to apoptosis and therefore might be uniquely suited for treatment by CSA [17]. Work in the swine has laid the foundations for the use of CSA. Initially, research was conducted to define the optimum cryogen dosimetry. This was followed by depth-of-injury work using endoscopic ultrasonography (EUS) and then comparative trials of CSA, MPEC and APC. Depth of injury at doses of 20 seconds times two cycles approximates 2 mm. Longer duration freezes achieve greater depths of injury [11].
It is unclear at this point what stages of esophageal cancer could potentially be treated/palliated with this modality. However, in this particular case and based on the degree of stricturing that followed it is likely that full esophageal wall thickness injury occurred. Thus palliation of tumors up to T4 (tumor invading adjacent structures) is conceivable.
The stricture that developed in this case was significant and required multiple interventions. Other potential complications of CSA include perforation, and bleeding. It is unknown what the actual complication rates are for this modality at this dose due to its relative novelty. In the first trial published by Johnston et al., no complications were reported. They used a dosimetry of 20 seconds times two for the first 10 patients. The CSA complication rate relative to other ablation techniques such as photodynamic therapy (PDT) is also unknown. However, for PDT the esophageal stricture rate is 30 to 50% depending on the number of treatments.
This particular malignancy may have been a very indolent one with slow growth as evidenced by the significant time interval between the first and second esophageal cancer presentation. It is also conceivable that only one CSA treatment was necessary for the palliation of this tumor in that "cure" is highly unlikely in such a case. One application of CSA may have avoided the subsequent stricture. However, this case still represents the first of its kind in the medical literature using this device and technique to achieve a sustained remission for SCCA of the esophagus. CSA has advantages relative to other palliative measures in that it is simple to use, can be performed with a standard diagnostic upper endoscope, is relatively inexpensive, and has a low rate of complications [12]. There is no photosensitivity as in PDT and most patients after CSA can resume eating and a normal lifestyle the same day. Although treatment of this patient resulted in a post treatment stricture, he has no evidence of recurrent malignancy two years post treatment. A sustained remission of this nature in recurrent SCCA is unusual. Although speculative, this sustained remission could relate to the unique mechanisms of action of CSA. These mechanisms of injury include the induction of apoptosis, cryonecrosis, and systemic anti-tumor immune stimulation [18-20]. The effectiveness of CSA in the treatment of neoplasms such as prostate cancer can also be enhanced by certain chemotherapeutic agents such as 5-fluorouracil [20]. These mechanisms of injury in concert with the method of delivery may make CSA an ideal option for the palliative treatment of esophageal neoplasms. Pilot studies indicate that mucosa damaged by cryotherapy followed by healing in an acid-free environment results in re-epithelialization with normal squamous epithelium in the majority of patients [12].
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