Treatment of Squamous Cell Carcinoma of the Esophagus Synchronously Associated with Head and Neck Cancer

Discussion

The association between ESCC and HNC is frequently recognized. In the current study, synchronous HNC was observed in 9.7% of the patients with ESCC. A nationwide registry of 5066 Japanese patients with esophageal cancer treated in 2004 showed that second cancers in another organ were present in 981 patients (19.4%). Gastric cancer was the most common form of cancer (353 lesions), followed by H&N cancer, including 162 pharyngeal cancers, 66 laryngeal cancers and 24 cancers in the oral cavity (17). We previously reported that both heavy smoking and heavy drinking are well-established risk factors for HNC and ESCC, and for multiple occurrences of cancer in these areas (2, 18, 19); the current study revealed the synchronous combination of superficial ESCC and advanced HNC are most frequently recognized. Most ESCC lesions were detected by screening endoscopy, which was performed for the purpose of deciding the treatment strategy for advanced HNC. We have routinely performed endoscopy for HNC patients, while the head and neck regions have also been routinely examined in ESCC patients. These data support the significance of surveillance for synchronous double cancer.

Associated HNC is one of the most significant problems in determining the treatment strategy for ESCC. Multiple factors must be considered when determining the treatment strategy, especially when the treatment will involve surgery (5, 20). In such cases, the curability of both cancers must be carefully evaluated based on an accurate assessment of the tumor stage. If both tumors are potentially curable, each lesion should be treated individually, as though each were a single distinctive, primary lesion. On the other hand, we have to consider not only the invasiveness of the treatment on the basis of the patient's general status and comorbidities, but also their quality of life after treatment, including the vocal and swallowing functions. Based on these concepts, the appropriate therapies for these double cancers are determined and various combination treatments have been applied, as shown in Table I.

Simultaneous definitive CRT has been difficult due to the wide radiation field. We have aggressively adopted this treatment and have previously reported its efficacy and feasibility (13, 14). In this study, we further analyzed the clinical effects, including recurrence and prognosis in 38 patients. As a result, definitive radiotherapy was completed in 95% of the patients. One patient deceased due to aspiration pneumonia during the treatment; however, the treatment was tolerable in the other patients. CRT was more effective for patients with earlier cancers of the esophagus as well as the head and neck (Table II). However, the clinical results in HN seemed to be more favorable than those in ESCC. All of the lesions of stage I HNC showed a CR after treatment, while the response rate was 67%, even in stage I esophageal cancer. Recurrence after CR is frequently recognized, even in early ESCC and the clinical results of the therapy for recurrent disease were not favorable. Furthermore, salvage therapy for either remnant or recurrent disease after CRT was more frequently available for HN, in comparison to ESCC. Total PLE was performed for a patient with a local recurrence of hypopharyngeal cancer. The patient remains alive without recurrence. However, this operation as a salvage treatment is reported to be extremely high-risk, with high rates of mortality (22%) and morbidity (44%), and should be carefully planned and conducted in selected centers of excellence (4). Long-term survival after definitive CRT was achieved in 44% of patients. These results indicate that simultaneous definitive CRT for double cancer is a feasible and effective treatment; however, ESCC may be more resistant to this type of therapy in comparison to HNC.

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Figure 2.

The overall survival after treatment. A. The overall survival curves in 91 patients with synchronous esophageal squamous cell carcinoma (ESCC) and head and neck cancer (HNC). B. The overall survival curves after simultaneous definitive chemoradiotherapy (CRT, thin line) and after simultaneous surgical resection (bold line).

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Figure 3.

The surgical procedures in staged operations that consisted of total pharyngo-laryngo-esophagectomy plus free jejunal transfer during the first stage and reconstruction with right hemi-colon interposition three weeks later. This application makes it possible to avoid microvascular anastomosis during the second-stage operation, in which fibrous adhesion would develop. Furthermore, it results in the easier management of saliva outflow.

Especially when surgical resection is adopted for synchronous ESCC and HNC, the surgical process, which includes the resection of both cancers and reconstruction, tends to be extremely invasive and complicated. Furthermore, it frequently results in a disturbance of the vocal and swallowing functions. We have aggressively indicated simultaneous surgical resection for such cases of double cancer, while adopting plastic surgery techniques, such as microvascular anastomosis and muscle flap, and staged operations (5, 6). Microvascular anastomosis is a useful technique for the resection of such double cancers. In such cases, the blood flow of the reconstructed conduits tends to be unstable and may result in serious necrosis. We have frequently adopted not only microvascular venous anastomosis (super-drainage) but also arterial anastomosis after total PLE, in order to stabilize the blood flow of the distal end of the reconstructed organ. Staged operations, that consist of an initial stage in which resection is performed and a secondary stage in which reconstruction is performed several weeks later, can reduce the surgical stress in high-risk operations. Staged operations were performed for high-risk patients with thoracic esophageal cancer (21). The original procedure was esophagectomy, cervical esophagostomy and tube-jejunostomy; this was followed by reconstruction three weeks later (21). This staged operation was performed in cases of extremely invasive total pharyngo-laryngo- esophagectomy by adopting pharyngostomy (22, 23). In the current case, we initially performed total PLE plus free jejunal transplantation, as previously reported (6). The proximal end of the jejunal graft was anastomosed to the pharynx and the distal end was used for the jejunostomy. Reconstruction with the right hemi-colon was performed secondarily. This approach makes it possible to avoid microvascular anastomosis during the second-stage operation, in which fibrous adhesion would develop. Furthermore, it results in the easier management of the saliva outflow.

The clinical outcomes, including mortality and morbidity, as well as prognosis after simultaneous resection were acceptable. These results indicate that simultaneous resection is an effective treatment option when appropriate techniques are applied for each case, such as staged operations and microvascular anastomosis, even in patients with double cancer of the esophagus and the head and neck.

The treatment strategy for synchronous ESCC and HNC must be decided after considering multiple factors, such as the stages of the respective tumors, the invasiveness of the therapies and the preservation of vital functions. Multiple combinations, based on the multidisciplinary therapy, are performed. Both simultaneous CRT and simultaneous resection are feasible and acceptable treatment options. Thus, the close cooperation of the medical staff, including surgeons from various fields and medical and radiological oncologists is essential.