Updates of perioperative multidisciplinary treatment for surgically resectable esophageal cancer.

Esophageal cancer has one of the poorest prognoses among all cancer types, due to the propensity for an early spread through the lymphatics and the difficulty to perform surgical treatment. To improve the prognosis, the management of esophageal cancer has been developed through the conduct of several clinical trials worldwide. In western societies, neoadjuvant chemoradiotherapy has been established as the standard treatment approach, as indicated by the results of the CROSS trial. Recently, the Japanese JCOG1109 trial demonstrated the significant improvement of survival by neoadjuvant triplet chemotherapy. As an adjuvant treatment, an immune checkpoint inhibitor has shown promising results in the CheckMate-577 trial. Including adjuvant S-1 mono therapy as another option, a randomised control phase III study will determine the ideal treatment for surgically resectable esophageal cancer. Furthermore, the efficacy and safety of neoadjuvant cisplatin +5-fluorouracil or DCF plus nivolumab are examined in the JCOG1804E (FRONTiER) study. In addition to definitive chemoradiation therapy, the SANO trial is examining the safety and efficacy of active surveillance after neoadjuvant chemoradiotherapy, which might give us the choice to adopt organ preservation approach. The development of treatment has progressed dramatically with the advent of immunotherapy. Considering the biomarkers to predict the treatment response and prognosis, individualised multidisciplinary treatment strategies should be established for esophageal cancer patients.

Lymph node metastatic patterns and the development of multidisciplinary treatment for esophageal cancer.

Abundant lymphatic flow and the anatomical location of the esophagus can result in the widespread distribution of lymph node metastasis of esophageal cancer from the cervical to the abdominal field. Historically, the Japan Esophageal Society and American Joint Committee on Cancer offer two different classifications of lymph node group location surrounding the esophagus. The location of sentinel lymph nodes in midthoracic esophageal cancer reflects the variety of lymphatic drainage routes. In fact, in cT1N0 esophageal cancer, pathological lymph node metastasis has been observed from the cervical to the abdominal field, and the locations were shown to be closely linked to the primary tumor location in advanced stages. While the impact of histology on the distribution of LN metastasis has been extensively debated, a recent prospective study on esophagogastric junction cancer found that metastatic patterns did not differ by histology. Thoracic duct lymph nodes were defined as one of the regional lymph node stations in the mediastinum. Although lymph node metastasis around the thoracic duct has occasionally been observed, the oncologic impact of thoracic duct lymph node dissection has not been fully elucidated. To eradicate tumors locoregionally, three-field lymph node dissection, a strategy for extended lymph node clearance, has been established. In esophagectomy, three-field lymph node dissection is defined as a procedure for complete regional cervico-thoraco-abdominal lymph node dissection. However, its therapeutic efficacy must be evaluated based on the balance between oncological outcomes and possible added surgical risk. To further improve survival, multidisciplinary treatment consisting of surgery, chemotherapy, and radiotherapy has been established worldwide as a standard treatment for esophageal cancer. Now that neoadjuvant therapy followed by esophagectomy is the standard, adding adjuvant therapy including immunotherapy could be a promising treatment option. The ideal combination of various multidisciplinary treatment approaches and extensive LN dissection need to be established to improve the oncological outcomes for EC patients.

Thyroid and Parathyroid Functions After Pharyngo-Laryngo-Esophagectomy for Cervical Esophageal Cancer.

BACKGROUND: Cervical esophageal cancer (CEC) patients whose larynx function cannot be preserved often undergo chemoradiotherapy, whereas those with residual or recurrent lesions undergo a pharyngo-laryngo-esophagectomy (PLE); however, some need to undergo a pharyngolaryngectomy with total esophagectomy (PLTE) for synchronous or metachronous esophageal cancer. We retrospectively evaluated the relationship between preoperative irradiation (or the extent of esophageal resection) and postoperative endocrine complications in CEC, including hypothyroidism and hypoparathyroidism. METHODS: The cancers of 35 (5.4%) of 678 esophageal cancer patients with esophagectomy treated in 2000-2017 were CECs. We also analyzed the 17 cases of CEC patients who underwent PLE with thyroid lobectomy-11 with irradiation before PLE and 6 without irradiation. Seven patients underwent a PLTE. RESULTS: Hypothyroidism and hypoparathyroidism occurred in 14 and 12 patients, respectively. The hypothyroidism rate was significantly higher in patients with irradiation versus those without irradiation (100% vs. 50%; p = 0.010), and the hypoparathyroidism rate was significantly higher in the PLTE versus non-PLTE patients (100% vs. 50%; p = 0.026). The mean levothyroxine dosage was 1.60 µg/kg/day in the PLE patients post-irradiation. CONCLUSIONS: Irradiation appears to be a risk factor for hypothyroidism after PLE with thyroid lobectomy, while PLTE might have some effect on hypoparathyroidism. Due to vocal function loss, PLE patients may experience symptoms from endocrine complications. Levothyroxine treatment soon after PLE for post-irradiation patients and patients requiring as-needed calcium or vitamin D supplementation based on biochemical hypocalcemia for PLE (especially PLTE), may be effective in preventing symptomatic endocrine complications.

The Benefits of Docetaxel Plus Cisplatin and 5-Fluorouracil Induction Therapy in Conversion to Curative Treatment for Locally Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND: Definitive chemoradiotherapy (CRT), used for treatment of patients with an initial diagnosis of unresectable locally advanced esophageal cancer, has led to unsatisfactory long-term prognosis. Moreover, CRT can lead to esophageal fistula, perforation, and strictures. Therefore, strong induction chemotherapeutic treatments are necessary to reduce the tumor volume for subsequent radical esophagectomy. This study aimed to determine the oncological utility of docetaxel plus cisplatin and 5-fluorouracil (DCF) and the technical feasibility of subsequent esophagectomy for locally advanced esophageal cancer. METHODS: Eighty-seven patients with clinical borderline unresectable T3 and T4 esophageal squamous cell carcinoma without distant metastases were included in this study. There were 44 patients in primary DCF group and 43 patients in definitive CRT group, and perioperative and long-term oncological outcomes were compared between the two groups. RESULTS: Twenty-two patients (50%) achieved R0 resection in the DCF group. Albeit not significant, the rate of curative treatment was higher in the DCF group than the definitive CRT group (p = 0.099). The overall survival (OS) and progression-free survival (PFS) were better with DCF than with definitive CRT (median OS, 29 vs. 17 months, p = 0.206; median PFS, 10 vs. 6 months, p = 0.020). Specifically, the OS of patients with a Charlson score of less than 3 among the DCF-treated patients tended to be better than those among the definitive CRT-treated patients. CONCLUSION: DCF and subsequent esophagectomy achieved R0 resection in 50% of the patients and was associated with better long-term oncological outcomes in patients with initially unresectable esophageal cancer if their systemic status is acceptable.

Current Advancement in Multidisciplinary Treatment for Resectable cStage II/III Esophageal Squamous Cell Carcinoma in Japan.

Multidisciplinary treatment comprising surgery, chemotherapy, and radiotherapy for resectable esophageal squamous cell carcinoma (ESCC) is widely used with improved prognosis. Transthoracic esophagectomy (TTE) with extended lymph node (LN) dissection, known as three field LN dissection, has been recommended for ESCC using open thoracotomy or the thoracoscopic approach. The Japan Clinical Oncology Group (JCOG) trial (JCOG1409) is investigating the patients' long term survival using the thoracoscopic approach that has been shown to reduce the incidence of postoperative respiratory complication. For perioperative treatment, neoadjuvant chemotherapy using cisplatin plus 5-fluorouracil (5-FU), has been accepted as the standard of care in Japan based on the JCOG9907 trial. In Western countries, neoadjuvant chemoradiotherapy was shown to prolong overall survival for esophageal cancer, including ESCC. Although surgery has been recognized as an initial curative treatment for esophageal cancer, definitive chemoradiotherapy is an alternative treatment for patients who are unable to undergo thoracotomy or who decline to undergo surgery. This article reviews multidisciplinary treatment advances for ESCC. However, current standard treatments are country dependent and the ongoing trial may help standardize ESCC treatment across various societies.

Adult cecoanal intussusception caused by cecum cancer: report of a case.

We report a case of cecoanal intussusception caused by cecum cancer in a 29-year-old woman. The patient presented to our hospital with a mass protruding from the anus. We manually pushed the mass back into the rectum and performed a gastrograffin enema, which showed a cup-shaped filling defect in the rectum. The defect was moved back to oral side with the pressure of the enema, revealing a tumor originating in the cecum. Colonoscopy showed a protrusion, 5 x 3 cm in size, in the cecum. Laparotomy confirmed that the tumor originated at the bottom of the appendix in the cecum. We performed partial resection of the cecum containing the tumor and appendix. The pathological finding was submucosal adenocarcinoma in adenoma. Cecoanal intussusception is extremely rare and, to our knowledge, this adult case represents the first report documented in the world scientific literature.