Chronic malnutrition affects approximately 20-57% of patients with head and neck cancer. Increased catabolism, anorexia, dysphagia, odynophagia, and aspiration are several factors leading to cancer cachexia and malnutrition in this population. Weight loss prior to and during head and neck cancer treatment portends a variety of treatment difficulties. Van Bokhorst-De Van Der Schueren et al found that a greater than 10% weight loss over a six month period was the most powerful predictor of major post-operative complications. With approximately 54% of head and neck cancer patients admitting to restricted diets of soft or pureed foods, other means of nutritional support are frequently necessary to prevent poor treatment outcomes. Due to this, the benefits of enteral nutritional support as an adjunct in the management of head and neck cancer have become well established.
Enteral feeding by open gastrostomy was first introduced in 1875 and was often considered a measure of last resort due to the up to 50% risk of major complications associated with the procedure[44, 45]. Although complication rates for open gastrostomy have vastly improved in the modern era, the introduction of the percutaneous endoscopic gastrostomy technique provided a less invasive and easily reproducible method for providing prolonged enteral support for medically complicated patients. Various methods of PEG tube placement have since been devised, with the most commonly referenced being the Gauderer-Ponsky, Sacks-Vine, Russell, and radiologic-assisted techniques. Common to all methods of PEG, however, is the insertion of either an endoscope, nasogastric tube, or the feeding tube itself through the oral cavity and pharynx to the stomach for gastric visualization and/or insufflation. Reported benefits of PEG over open gastrostomy placement include decreased pain, abdominal complications, and cost[4, 13, 44]. Nasogastric feeding, although easily placed and relatively non-invasive, has its own risks, including gastroesophageal reflux, nasal alar erosion and deformity, laryngeal irritation, inadvertent tube removal, and sinusitis, and is thus generally not considered a viable long-term option for enteral feeding[44, 45].
After Preyer published the first case of PEG site metastasis from an oropharyngeal primary HNSCC in 1989, the complication of incidental seeding of the gastric or abdominal wall following PEG has become a developing concern. Several theories of the pathogenesis of this occurrence have been proposed, including direct implantation of malignancy at the time of tube placement, physiologic shedding of malignant cells into the alimentary tract with seeding of the PEG site after tube placement, and hematogenous spread with selective preference of circulating tumor cells to implant at the traumatized tissue of the PEG wound[15, 49].
Although the incidence of PEG site metastases is low, estimated at 0.5 – 3%[2, 4, 13, 50], survival outcomes indicate that this complication carries a grave prognosis. The estimated survival rate of 12.9% shown in the present review, although seemingly better than that reported for other sites of distant metastatic disease in HNSCC (1–6.5%)[51, 52], is likely a gross overestimation as available follow up in the case reports reviewed was well below five years. In addition, 64% of patients diagnosed with PEG site disease either had simultaneous or subsequent locoregional or distant metastatic disease, suggesting that PEG site metastases may be a marker of aggressive tumor behavior.
Presentations of PEG site metastasis include incidental imaging findings on metastatic work-up, vague abdominal discomfort, constipation, grossly evident tumor emanating from the abdominal wall, ulceration, and persistent stomal drainage. Some of these findings lack specificity, however, due to the fact that common complications of PEG, including stomal leakage of gastric secretions and formation of granulation tissue, may mimic tumor. Thus, knowledge of this complication and continued vigilance by all members of the head and neck oncologic team are critical to early detection, which might provide some hope for curative treatment.
Based upon the theories for the pathogenesis of PEG site metastases, especially that of direct tumor implantation, many procedural recommendations have been made for its avoidance. As the majority of reported cases of PEG site metastasis are associated with the Gauderer-Ponsky technique (96.6%), authors have suggested use of alternate techniques, such as Russell (transabdominal introduction of gastrostomy tube under endoscopic visualization), Sacks-Vine (blind pulling of the feeding tube through the abdominal wall via the mouth under nasogastric stomach insufflation), or radiologic-assisted to avoid passage of the feeding tube, endoscope, or both, past the site of the tumor. The Russell, or “push”, technique has been suggested to be a preferable compromise between ease of performance and risk of procedure for PEG placement in HNSCC patients[2, 16, 52]. Although this technique obviates the need to pull the feeding tube through the oral cavity and pharynx, an endoscope is still required for visualization within the stomach during feeding tube insertion through the abdominal wall. In 2003, Tucker et al reviewed 79 HNSCC patients undergoing PEG, 29 via the push technique and 50 via the pull technique. The authors found a 0% complication rate with push PEGs compared to 30% in those undergoing pull PEGs. One patient undergoing pull technique PEG presented with a PEG site metastasis, but the small study population size and overall low rate of PEG metastasis makes this result difficult to interpret when comparing the two methods. Theoretically, however, the smaller caliber and maneuverability of the endoscope should allow less trauma to the tumor surface than a blindly passed feeding tube, as is required with pull techniques such as Gauderer Ponsky or Sacks-Vine. The same argument has been made regarding the percutaneous placement of feeding tubes under fluoroscopic guidance in cases of HNSCC requiring enteral feeding[50, 53]. The paucity of published reports of PEG site metastasis from HNSCC using the percutaneous radiologic-assisted gastrostomy or the Russell technique tends to suggest that direct implantation of malignant cells at time of tube placement is the most plausible explanation for PEG site seeding. Data from the current series may also be interpreted to indirectly support this theory. The shorter time interval from PEG placement to diagnosis of PEG site disease (7.96 months) compared with timing of presentation of distant metastases established via hematogenous seeding (median 12 months) can be argued to reflect a larger initial metastatic deposit, as would be expected from implantation of tumor liberated by direct trauma to an existing tumor mass. Douglas et al, using tumor kinetic assumptions, hypothesized a bimodal distribution of PEG metastases with those appearing quickly most likely representing direct tumor implantation, and those appearing after a prolonged period (> 12 months) being a result of hematogenous spread. Of the 39 cases in which time from PEG placement to identification of PEG metastasis was reported, only 6 had intervals greater than 12 months. The fact that the only reported case of PEG site metastasis following fluoroscopic-guidance presented 14 months after tube placement, also weakly supports hematogenous metastatic implantation. Lastly, use of open gastrostomy, which also avoids the need for passage of an endoscope or feeding tube past the tumor site, may be a reasonable option in select patients, such as those with bulky tumors undergoing general anesthesia for other indications.
In addition to surgical alterations to prevent metastatic complications, changes in procedure timing and adjunctive modalities should also be considered. Alteration in timing of PEG tube placement in relation to HNSCC therapy has been analyzed as a potential strategy for prevention of stomal metastasis. The concept of direct tumor seeding has been implicated in other phenomena, namely stomal recurrence after total laryngectomy[54, 55]. Analysis of seventeen cases of peristomal recurrence of squamous cell carcinoma following total laryngectomy found pre-laryngectomy tracheostomy to be the sole significant risk factor for occurrence, with direct stomal implantation of tumor cells the hypothesized mode of transmission. Although early advocates of PEG in head and neck cancer patients recommended pre-treatment tube placement to provide earlier nutritional support, our review revealed that 89% of PEG site metastases occurred in patients undergoing PEG prior to initiation of definitive therapy. With this in mind, future research may be indicated to assess the benefit of deferring PEG placement until after initiation of radiotherapy or tumor resection. Similarly, prophylactic irradiation of the PEG site, especially in patients with bulky pharyngeal disease is an option shown to be of merit in other malignancies and tumor implantation locations. Prophylactic radiation given before pre-laryngectomy tracheostomy has been shown to decrease the incidence of peristomal recurrence, although at the cost of increased regional failure. For small-cell lung cancer, prophylactic cranial irradiation is well-established as standard of care to prevent metastasis and improve 3-year survival. Prospective studies to investigate the use of prophylactic PEG irradiation will be needed to assess the feasibility and benefit in the HNSCC patient population. Lastly, tumor-cell attachment inhibitors such as dispase have been shown to block metastatic implantation at surgical wound sites and may hold promise for the prevention of implantation at PEG sites.