A case of hypopharyngeal cancer with stenosis, perforation, and pyogenic spondylitis development after chemoradiotherapy

Introduction: Chemoradiotherapy plays an important role in preserving function and morphology in head and neck cancer. However, in a few cases, chemoradiotherapy has been shown to result in late complications, such as hypopharyngeal perforation, which is very rare. Presentation of case: A 65-year-old man, who had undergone chemoradiotherapy for hypopharyngeal cancer 30 months previously, presented with high fever and neck pain. He subsequently developed hypopharyngeal stenosis, hypopharyngeal perforation, and a retropharyngeal abscess followed by pyogenic spondylitis. He underwent surgical treatment (resection with reconstruction) and was administered an antibacterial agent and steroids for an extended period. This treatment regimen was successful, and the patient has survived disease-free without symptoms. Discussion: Chemoradiotherapy-induced hypopharyngeal perforation is an extremely rare condition. In the present case, the perforation was large (2 cm), and the hypopharyngeal cavity was originally constricted. Pharyngeal reconstruction with a jejunal autograft was therefore necessary. Through the present case, we reconfirmed that although the primary purpose of chemoradiotherapy is organ preservation, it can also lead to organ destruction and fatal complications. It is important that physicians be aware of the possibility of hypopharyngeal perforation so as to avoid delayed diagnosis and treatment of similar rare cases. Conclusion: Hypopharyngeal perforation can sometimes be fatal because it can lead to pyogenic spondylitis. Suitable surgical techniques and appropriate doses of antibacterial agents for long-term use were appropriate treatments for the patient in this case

Induction of CD44 variant 9-expressing cancer stem cells might attenuate the efficacy of chemoradioselection and Worsens the prognosis of patients with advanced head and neck cancer.

At our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30-40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chmoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC).Through a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies.The intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9 positivity (HR: 3.145, 95% CI: 1.235-8.008, P = 0.0163) was significantly correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95% CI: 1.054-9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9-induced group was significantly (P = 0.04) worse than the CD44v9-non-induced group.CCRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy to enhance the efficacy of chemoradioselection and consequent organ preservation and survival

Representative pictures of anti-CD44v9-antibody immunostaining.

<p>The staining intensity obtained in the basal cells of normal epithelium was used as a control (A). Tumor samples demonstrated strong (B), moderate (C), and weak (D) intensities relative to the control (A). Respective positive (E) and negative <u>(F</u>) stainings. Bar indicates 200 um.</p

(A) Disease specific survival curves of all patients (n = 102) according to the chemoradioselection.

<p>(B) Disease specific survival curves based on the CD44 v9 positivity of biopsy samples (n = 60) obtained from 30 chemoradioselected (CRS) patients and 30 non-chemoradioselected (N-CRS) patients. (C) Disease specific survival curves based on the CD44 v9 positivity of biopsy samples obtained from 30 N-CRS patients.</p

(A) Disease specific survival curves based on the CD44 v9 positivity of surgically removed samples obtained from 72 non-chemoradioselected (N-CRS) patients.

<p>(B) Diseasespecific survival curves of 30 N-CRS patients who had paired biopsy and surgically removed samples. The patients were divided into 2 groups according to their levels of CD44v9 expression before and after concurrent chemoradiotherapy.</p

Proposed roles of CD44v9-expressing CSC and non-CSC in the chemoradioselection.

<p>(A) CD44v9-expressing non-CSCs are sensitive to CCRT. Intrinsic CD44v9-expressing CSCs (B) or CCRT-induced CD44v9-expressing CSCs (C) can survive CCRT. These CD44v9-expressing CSCs are considered to be highly invasive and metastatic. CSC, cancer stem cell; CCRT, concurrent chemoradiotherapy; CRS, chemoradioselected; and N-CRS, non-chemoradioselected.</p

Patient characteristics (<i>N</i> = 102).

<p>Patient characteristics (<i>N</i> = 102).</p