Metastatic Carcinoma to Percutaneous Endoscopic Gastrostomy Tube Sites. A Report of Five Cases

Transcription

1 Metastatic Carcinoma to Percutaneous Endoscopic Gastrostomy Tube Sites A Report of Five Cases Lanjing Zhang, MD, MS, 1,2 Stephanie A. Dean, MD, 1 Emma E. Furth, MD, 1 Gregory S. Weinstein, MD, 3 Virginia A. LiVolsi, MD, 1 and Kathleen T. Montone, MD 1 From the 1 Departments of Pathology and Laboratory Medicine and 3 Otorhinolaryngology, Head and Neck Surgery, University of Pennsylvania Medical Center, Philadelphia, PA; and 2 Department of Pathology, University Medical Center of Princeton at Plainsboro, Plainsboro, NJ, and Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. Key Words: Squamous cell carcinoma; Metastasis; Percutaneous endoscopic gastrostomy; Head and neck cancer; Survival ABSTRACT Objective: To characterize the clinicopathologic features of metastatic carcinomas at percutaneous endoscopic gastrostomy (PEG) tube sites. Methods: We reviewed the metastatic malignancies at PEG tube sites ( ). Results: Five patients were identified, each with primary head and neck keratinizing squamous cell carcinoma. The metastases had a mean size of 6.08 cm (95% confidence interval [CI], ). The time from PEG tube placement to metastasis diagnosis was 9.8 months (95% CI, ). The survival times from PEG tube placement and from metastasis diagnosis were 23.5 (95% CI, ) and 13.7 (95% CI, ) months, respectively. Compared with a meta-analysis of the largest case series, our male patients were significantly older (mean, 73 years; 95% CI, vs mean 59 years, 95% CI, ) but had similar survival times. Conclusions: Despite their older ages, our male patients had similar survival times to those reported previously. Larger series are needed to confirm our findings and explore the causes. Oral cavity and laryngeal cancer is the eighth most common cancer in American men, with an estimate of 27,100 new cases occurring each year. The male and female death rates have significantly decreased to 3.85% and 1.27% in 2007, respectively, an approximately 30% reduction from Percutaneous endoscopic gastrostomy (PEG) was first described for treating esophagogastric cancer in Its use for head and neck (ENT) cancers, either prophylactically or postoperatively, has significantly improved the quality of life and nutritional status of patients with ENT cancer, but the benefits of prophylactic PEG are controversial. The major complications of PEG are rare (7%-12%) and include PEG tube displacement, gastric or esophageal perforation, metastasis, bleeding, and infection. 2,3 Metastasis to the PEG tube site is a rare but significant complication of ENT cancers, with a reported incidence of 0.5% to 1%. 4-6 Only fewer than 50 cases have been reported, and the largest series with survival data consists of no more than three cases. 7 We characterize herein the clinical and pathologic features of five ENT carcinomas that metastasized to the PEG tube sites and compared our data to those from a previous meta-analysis of the largest number of cases. 6 Materials and Methods We conducted a laboratory information system search for matched cases from January 2002 to September 2012 using the combined terms of gastrostomy and carcinoma. Only cases that met the following criteria were included: (1) the medical charts confirmed the clinical history of ENT cancer and PEG tube placement; (2) the metastatic tumor at the PEG 510 Am J Clin Pathol 2014;141: Downloaded 510 from

2 tube site was confirmed by comparing with the primary tumor; and (3) the histology slides of the metastasis at the PEG tube site were available for review. The institutional review board (IRB) determined that an IRB review was not required because all the patients had died by the time of this study. We extracted the following data for each matched case if available: (1) patient age at the time of PEG tube placement; (2) patient sex and ethnicity; (3) presenting symptom; (4) the site, grade, size, perineural and vascular invasion, tumor stage, and treatment of the primary tumor; (5) the site, grade, size, and treatment of the PEG tube site metastatic tumor; (6) the interval between the metastasis diagnosis and PEG tube placement; (7) the survival from the time of metastasis diagnosis; (8) the survival from the time of PEG tube placement; (9) presence of metastatic tumor at the time of metastasis diagnosis; and (10) the PEG tube placement year. Two investigators (L.Z. and S.A.D.) independently verified the extracted data. Statistical analysis was performed using Stata (version 11, StataCorp, College Station, TX). The two-tailed 95% confidence interval (95% CI) was calculated by using normal distribution. We also calculated the 95% CI of related parameters of the cases summarized by Cappell. 6 The negative lower 95% CI limits, presumably resulting from our small sample size, were converted to 0 for lack of meaningful clinical significance. Differences were considered statistically significant (P <.05) only when the 95% CIs of the two groups did not overlap. Results We identified five PEG tube site metastasis cases that met the aforementioned inclusion criteria, all of which were keratinizing squamous cell carcinomas (SCCs). The clinical and pathologic data are summarized Table 1 and Table 2. The five patients included two white men, two Hispanic white men, and one white woman, with a male to female ratio of 4:1. The average patient age was 70 ± 3.8 years (range, 59 to 80 years; 95% CI, years). The patients included in Cappell s meta-analysis 6 were of similar age as our patients but were significantly younger than our male patients (ie, no 95% CI overlap, Table 2). Of our five patients, one presented with PEG tube reflux (backflow of the PEG tube contents into the tube, probably because of tube lumen narrowing, partial obstruction, or excessive feeding or gastric pressure), Table 1 Characteristics of the Metastatic Head and Neck SCCs to the PEG Tube Site Characteristic Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Age at the time of PEG tube placement, y Sex Male Male Female Male Male Ethnicity/race Hispanic/white Hispanic/white White White White Presenting symptom NA PEG tube reflux NA GI bleeding NA Primary SCC site Posterior pharyn- Left lateral and tip Base of tongue Base of tongue Posterior geal wall of tongue pharyngeal wall Primary SCC grade Poorly Moderately to poorly Moderately Poorly Moderately differentiated differentiated differentiated differentiated differentiated Primary tumor perineural None None NA Lymphovascular invasion None (on biopsy) and vascular invasion present; no neural invasion Primary tumor size, cm NA 2.0 NA Primary tumor stage (AJCC) T4N1M0 T2N2M0 Unresectable mass T2N2M0 Unresectable mass Treatment for primary tumor Resection, chemo- Resection, chemo- Chemoradiation Resection, chemoradiation, Chemoradiation and radiation, and radiation, and and neck and neck dissection neck dissection neck dissection neck dissection dissection PEG tube site metastatic Poorly Moderately Moderately Poorly Moderately SCC grade differentiated differentiated with differentiated differentiated differentiated hepatoid features PEG tube site metastatic tumor 9.2 No resection done ( size, cm (by pathology report) 5.0 mass clinically) Treatment for PEG metastasis NA None Partial gastrectomy Partial gastrectomy Partial gastrectomy Metastatic time from PEG tube placement, mo Overall survival after metastasis, mo Overall survival after PEG tube placement, mo Metastatic tumor of None Granulation tissue None Metastasis to omental None other site at the time vs metastasis at lymph node (PET report) of PEG metastasis the base of neck by radiology report PEG placement year AJCC, American Joint Committee on Cancer Cancer Staging System; GI, gastrointestinal; NA, not available; PEG, percutaneous endoscopic gastrostomy; PET, positron emission tomography; SCC, squamous cell carcinoma. Downloaded from Am J Clin Pathol 2014;141:

3 Zhang et al / Metastatic Carcinoma to PEG Tube Sites one with gastrointestinal bleeding, and three with no specific documented complaints. All patients had moderately or poorly differentiated primary ENT SCC, including three in the tongue and two in the posterior pharyngeal wall. They were all treated with neck dissection and postoperative chemoradiation therapy. Three of them had primary tumor resection, and the other two had tumors deemed unresectable. Only one of the primary tumors showed lymphovascular invasion. A partial gastrectomy was performed to resect the metastasis in three patients, whereas the other two patients were not deemed to be surgical candidates. The mean size of metastatic tumors at the PEG tube site was 6.08 ± 0.84 cm (range, cm; 95% CI, cm). All the metastatic tumors were morphologically similar to the primary tumors. The mean time from the PEG tube placement to metastasis was 9.8 ± 1.16 months (range, 7-13 months; 95% CI, months), which is not significantly different from the cases summarized by Cappell 6 (see Table 2). The mean postmetastasis overall survival was 13.7 ± 6.26 months (range, months; 95% CI, months) for all patients and 9.00 ± 1.08 months (range, months; 95% CI, months) for the male patients. The mean survival from the time of PEG tube placement was 23.5 ± 5.71 months (range, months; 95% CI, months) for all patients and ± 7.37 months (range, months; 95% CI, months) for the male patients. No survival difference was found among our patients as a whole, our male patients, and the patients summarized in Cappell s meta-analysis. 6 One of the patients had omental lymph node metastasis as shown by positron emission tomography scan; interestingly, he still had a survival of 21 months since the metastasis diagnosis and a survival of 30 months since the PEG tube placement. Otherwise, no documented metastasis was found in our patients at the time of PEG tube site metastasis diagnosis. Discussion ENT carcinoma is one of the most common cancers in men. Such a male predominance is also seen in our case series (male to female ratio, 4:1). The 5-year survival rate of ENT cancer has increased from 53% in to 63% in Many factors played a role in increasing the survival rates and improving patient s quality of life, including advancements in chemoradiation therapy regimens, surgical techniques, and pathologic markers predicting chemoresistance. PEG tube placement has proved useful in improving quality of life and preventing malnutrition in patients with ENT cancer. Several complications are associated with PEG, such as bleeding, infection, perforation, and tube displacement. 2,3 In addition, cancer metastasis, possibly through seeding, is considered a rare but severe complication of PEG tube placement. 6 Its incidence is reported as 0.93% in a study of 304 patients. 5 Similarly, a survey from England found PEG tube metastasis in approximately 5% of surveyed units over 3 years. 8 So far, fewer than 50 cases have been published, and the largest series only included three cases. 7 Thus, to our best knowledge, this is the largest case series with survival data. Because we had only five cases, it was possible for us to characterize the post-peg tube placement survival (mean, 23.5 months; 95% CI, months) and metastatic tumor size (mean, 6.08 cm; 95% CI, cm), which was not carried out by Cappell. 6 Our survival data may shed light on the prognosis of the patients with PEG tube site metastasis, and our metastatic tumor size data may help differentiate metastasis from other mass-like lesions. Two groups of risk factors, pathologic and therapeutic, have been proposed for PEG tube site metastasis in the meta-analysis by Cappell. 6 Our data agree with all of the proposed histologic risk factors, including carcinoma type, site of the primary tumor, tumor grade (moderately or poorly differentiated), and advanced cancer stage. Table 2 Comparison of Clinicopathologic Features of Patients in Our Study and Those in the Largest Case Series in the Literature a All Patients Male Patients Patients in Meta-analysis No. Mean (SE) 95% CI No. Mean (SE) 95% CI No. Mean (SE) 95% CI Age, y (3.83) (3.41) b (1.5) b Time from PEG placement to (1.16) (1.08) (0.81) metastasis diagnosis, mo Survival from metastasis (6.26) (8.03) (0.72) diagnosis, mo Survival from PEG (5.71) (7.37) NA placement, mo Metastatic tumor size, cm (0.84) (1.08) NA Primary tumor size, cm (1.87) (1.87) (0.48) CI, confidence interval; NA, not available; PEG, percutaneous endoscopic gastrostomy; SE, standard error. a Meta-analysis conducted by Cappell. 6 b No overlaps seen in 95% confidence intervals. 512 Am J Clin Pathol 2014;141: Downloaded 512 from

4 In addition, we report PEG tube reflux as a novel presentation of the metastasis to the PEG tube site, which has not been reported according to our literature search. Caregivers should be alerted and should consider the possibility of a metastasis when a high-risk patient has PEG tube reflux. PEG tube reflux, however, may be associated with other etiologies, such as excessive feeding or gastric pressure, (partial) clogging of the PEG tube, and a mechanical problem with the tubing itself. A pathologic examination may be warranted. Our other patient with documented complaints presented with bleeding, a known presentation for metastasis. There was no significant difference between our patients, including the male subgroup, and the reported cases (Table 2) 6 with regard to the survival times and the interval between the PEG tube placement and metastasis diagnosis. However, our male patients were significantly older than those described by Cappell 6 (mean, 73.0 years; 95% CI, years vs mean, 59.0 years; 95% CI, years). Given the independent prognostic value of age, 9 it is therefore likely that our patients had some survival benefits despite their older ages. Several factors may be considered while further studies are needed to confirm our speculations. First, all five of our patients had been treated with neck dissection and chemoradiation therapy for the primary tumors, and two had undergone complete resection. Indeed, our prior data showed that combined selective neck dissection and chemoradiation therapy are beneficial in controlling local recurrence and improving tumor response. 10,11 It is possible that such a combined treatment, not widely adopted at the time, may have delayed the metastasis and/or prolonged postmetastasis survival. Second, all three of our patients with longer survival received partial gastrectomy for the metastatic tumors. The factors derived from the previous observation may have been associated with the better survival rates, including tumor resectability, tolerance to surgery, and tumor burden/mass reduction. Our experience also suggests that one should pursue a partial gastrectomy in these patients if feasible. However, larger controlled studies are needed to confirm our finding but may be difficult because of the rarity of this entity. Two modalities or alternatives of PEG should be discussed in light of our findings. An alternative to PEG is percutaneous radiologic gastrostomy (PRG), a radiologically guided procedure (fluoroscopic placement) as the name implies. However, PRG is associated with more early (22.8% vs 10.8%) and late (23.8% vs 10.1%) complications than PEG, but a similar 7-day mortality rate (3.1% vs 4.5%). 12 Interestingly, a recent article also suggests that PRG is less expensive and linked to a similar rate of minor complications compared with PEG. 13 Technical advancement and operator experience may contribute to fewer complications and may promote the use of PRG in patients with ENT cancer. However, data available are limited at present, and more studies are still needed to validate the benefits and risks of PRG. Prophylactic PEG, a relatively new modality, may decrease patient malnourishment rate by 10%, improve patient quality of life, and prevent weight loss, as shown in a 2-year follow-up study. 14 However, another report argues that most prophylactic PEG may be unnecessary or unused. 15 Our data and prior reports are not in favor of prophylactic PEG use for patients with ENT cancer, because the risk of metastasis and/or tumor seeding is significantly higher in the cases with viable tumor, that is, before chemoradiation treatment. 5,6 In the meantime, we agree that the benefits and risks of prophylactic PEG are largely unclear and deserve more research efforts. Besides the small sample size, our study has other limitations. First, this is a single institution experience. Patient selection bias may exist. Second, no exact P values could be calculated for comparing our series and the meta-analysis because of a lack of data on individual patients. 6 Third, no detailed chemoradiation therapy regimens were available because the patients all returned to see their local oncologists for follow-up. Nonetheless, our case series cannot substitute any clinical trials focusing on this subject. In summary, we report five cases of ENT SCC metastasis to the PEG tube site. Our male patients had similar post PEG tube placement and postmetastasis survival rates despite their older ages. The survival benefits may be related to the partial gastrectomy for the metastasis and/or combined treatment of neck dissection, chemoradiation therapy, and resection for the primary lesions. One novel presentation of the metastasis as seen in one of our patients is PEG tube reflux (backflow of the PEG tube contents into the tube), which should raise a concern for metastasis and warrant careful investigation. Future large-scale studies may help substantiate our findings on this rare and unique complication of PEG tube placement. Address reprint requests to Dr Montone: Dept of Pathology, 6 Founders, 3400 Spruce St, Philadelphia, PA 19104; Kathleen. Montone@uphs.upenn.edu. References 1. den Hartog Jager FC, Bartelsman JF, Tytgat GN. Palliative treatment of obstructing esophagogastric malignancy by endoscopic positioning of a plastic prosthesis. Gastroenterology. 1979;77: Zuercher BF, Grosjean P, Monnier P. Percutaneous endoscopic gastrostomy in head and neck cancer patients: indications, techniques, complications and results. Eur Arch Otorhinolaryngol. 2011;268: Van Dyck E, Macken EJ, Roth B, et al. Safety of pulltype and introducer percutaneous endoscopic gastrostomy tubes in oncology patients: a retrospective analysis. BMC Gastroenterol. 2011;11:23. Downloaded from Am J Clin Pathol 2014;141:

5 Zhang et al / Metastatic Carcinoma to PEG Tube Sites 4. Maccabee D, Sheppard BC. Prevention of percutaneous endoscopic gastrostomy stoma metastases in patients with active oropharyngeal malignancy. Surg Endosc. 2003;17: Cruz I, Mamel JJ, Brady PG, et al. Incidence of abdominal wall metastasis complicating PEG tube placement in untreated head and neck cancer. Gastrointest Endosc. 2005;62: ; quiz 52, Cappell MS. Risk factors and risk reduction of malignant seeding of the percutaneous endoscopic gastrostomy track from pharyngoesophageal malignancy: a review of all 44 known reported cases. Am J Gastroenterol. 2007;102: Sheykholeslami K, Thomas J, Chhabra N, et al. Metastasis of untreated head and neck cancer to percutaneous gastrostomy tube exit sites. Am J Otolaryngol. 2012;33: Barber AJ, Lowe D, Lal S, et al. Survey of gastrostomy insertion technique used in oncology patients in UK oral and maxillofacial units. J Craniomaxillofacial Surg. 2010;38: Datema FR, Ferrier MB, Vergouwe Y, et al. Update and external validation of a head and neck cancer prognostic model. Head Neck. 2012;35: Weinstein GS, Quon H, O Malley BW Jr, et al. Selective neck dissection and deintensified postoperative radiation and chemotherapy for oropharyngeal cancer: a subset analysis of the University of Pennsylvania transoral robotic surgery trial. Laryngoscope. 2010;120: Machtay M, Rosenthal DI, Chalian AA, et al. Pilot study of postoperative reirradiation, chemotherapy, and amifostine after surgical salvage for recurrent head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2004;59: Silas AM, Pearce LF, Lestina LS, et al. Percutaneous radiologic gastrostomy versus percutaneous endoscopic gastrostomy: a comparison of indications, complications and outcomes in 370 patients. Eur J Radiol. 2005;56: Galaski A, Peng WW, Ellis M, et al. Gastrostomy tube placement by radiological versus endoscopic methods in an acute care setting: a retrospective review of frequency, indications, complications and outcomes. Can J Gastroenterol. 2009;23: Silander E, Nyman J, Bove M, et al. Impact of prophylactic percutaneous endoscopic gastrostomy on malnutrition and quality of life in patients with head and neck cancer: a randomized study. Head Neck. 2012;34: Madhoun MF, Blankenship MM, Blankenship DM, et al. Prophylactic PEG placement in head and neck cancer: how many feeding tubes are unused (and unnecessary)? World J Gastroenterol. 2011;17: Am J Clin Pathol 2014;141: Downloaded 514 from