The combination of docetaxel, cisplatin, and 5‐fluorouracil (DCF) as preoperative treatment for esophageal squamous cell carcinoma (ESCC) has not been investigated. We carried out a multicenter phase ...II feasibility study of preoperative chemotherapy with DCF for ESCC. Patients with clinical stage II/III ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy consisted of i.v. docetaxel (70–75 mg/m2) and cisplatin (70–75 mg/m2) on day 1, and continuous infusion of fluorouracil (750 mg/m2/day) on days 1–5. Antibiotic prophylaxis on days 5–15 was mandatory. This regimen was repeated every 3 weeks with a maximum of three cycles allowed. After completion of chemotherapy, esophagectomy with extended lymphadenectomy was carried out. The primary endpoint was the completion rate of protocol treatment. Forty‐two eligible patients were enrolled. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (83%), anorexia (7%), and stomatitis (5%). Forty‐one (98%) patients underwent surgery. The completion rate of protocol treatment was 90.5% (38/42). No treatment‐related death was observed and the incidence of operative morbidity was tolerable. According to RECIST, the overall response rate after the completion of DCF was 64.3%. Pathological complete response was achieved in 17%. The estimated 2‐year progression‐free survival and overall survival were 74.5% and 88.0%, respectively. Although these data are preliminary, preoperative DCF was well tolerated. Antitumor activity was highly promising and warrants further investigation. This trial was registered with University Hospital Medical Information Network (no. UMIN000002396).
A three-arm Phase III trial was started in November 2012. Preoperative chemotherapy with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced esophageal cancer in ...Japan, while preoperative chemoradiotherapy with cisplatin plus 5-fluorouracil is the standard in Western countries. Preoperative chemotherapy with docetaxel, cisplatin plus 5-fluorouracil is another promising regimen. The purpose of this study is to confirm the superiority of docetaxel, cisplatin plus 5-fluorouracil over cisplatin plus 5-fluorouracil and the superiority of cisplatin plus 5-fluorouracil with chemoradiotherapy over cisplatin plus 5-fluorouracil as preoperative therapy for squamous cell carcinoma of esophagus. A total of 501 patients will be accrued from 41 Japanese institutions within 6.25 years. The primary endpoint is overall survival and the secondary endpoints include progression-free survival, %R0 resection, response rate, pathologic complete response rate and adverse events.
Recurrent laryngeal nerve paralysis (RLNP) after esophagectomy is a common complication and associated with aspiration pneumonia. In this study, we assessed the risk of RLNP and the usefulness of ...immediate reconstruction of recurrent laryngeal nerve (RLN) to prevent respiratory complications after esophagectomy. Seven hundred and eighty-two consecutive patients underwent an esophagectomy with three-field lymph node dissection, simultaneous gastric conduit reconstruction, and cervical anastomosis. Vocal cord function was observed using a flexible laryngoscope. Reconstruction between RLN and ipsilateral vagus nerve was performed during esophagectomy. RLNP was observed in 229 (29.3%) of the patients after esophagectomy: 198 unilateral and 31 bilateral cases. Of the 198 unilateral RLNP, vocal cord paralysis was observed predominantly on the left side (82.7%). RLNP was significantly associated with postoperative respiratory complications (P < 0.001) requiring a tracheotomy (P < 0.001) and mechanical ventilation (P < 0.001) and was also associated with esophagogastric anastomotic leakage (P = 0.015); consequently, the postoperative hospital stay was longer for patients with RLNP (P < 0.001). A longer operation time (P < 0.001) and advanced age (P = 0.038) were identified as significant independent predictors of RLNP. Resection of the RLN together with metastatic nodes was performed in 29 cases. The patients underwent RLN reconstruction (n = 11) had a significantly shorter postoperative hospital stay than those without RLN reconstruction (n = 18) (P = 0.019). In conclusion, RLNP was related to a poorer postoperative course among patients undergoing an esophagectomy. New surgical technologies are recommended for prevention of RLNP.
Background
Postoperative pulmonary complications (PPCs) are the most common causes of serious morbidity after esophagectomy, which involves both thoracic and abdominal incisions. Although the ...thoracoscopic approach decreases PPC frequency after esophagectomy, it remains unclear whether the frequency is further decreased by combining it with laparoscopic gastric mobilization. This study aimed to determine the impact of laparoscopy on the prevention of PPCs after thoracoscopic esophagectomy using data from the Japan Clinical Oncology Group Study 0502 (JCOG0502).
Methods
JCOG0502 is a four-arm prospective study comparing esophagectomy with definitive chemo-radiotherapy. The use of thoracoscopy and/or laparoscopy was decided at the surgeon’s discretion. PPCs were defined as one or more of the following postoperative morbidities grade ≥2 (as per Common Terminology Criteria for Adverse Events v3.0): pneumonia, atelectasis, and acute respiratory distress syndrome.
Results
A total of 379 patients were enrolled in JCOG0502. Of these, 210 patients underwent esophagectomy via thoracotomy with laparotomy (
n
= 102), thoracotomy with laparoscopy (
n
= 7), thoracoscopy with laparotomy (
n
= 43), and thoracoscopy with laparoscopy (
n
= 58). PPC frequency was reduced to a greater extent by thoracoscopy than by thoracotomy (thoracoscopy 15.8%, thoracotomy 30.3%;
p
= 0.015). However, following thoracoscopic esophagectomy, laparoscopy failed to further decrease the PPC frequency compared with laparotomy (laparoscopy 15.5%, laparotomy 16.3%;
p
= 1.00). Univariable analysis showed that thoracoscopy (shown above) and less blood loss (<350 mL 16.3%, ≥350 mL 30.2%;
p
= 0.022) were associated with PPC prevention, whereas laparoscopy showed a borderline significant association (laparoscopy 15.4%, laparotomy 26.9%;
p
= 0.079). Multivariable analysis also showed that thoracoscopy and less blood loss were associated with PPC prevention.
Conclusion
Thoracoscopic approach to esophagectomy significantly reduced PPC frequency with minimal additional effect from laparoscopic gastric mobilization.
Objective Chemoradiotherapy is a popular definitive therapy for esophageal carcinoma among many patients and oncologists. Although the complete response rates are high and short-term survival is ...favorable after chemoradiotherapy, persistent or recurrent locoregional disease is frequent. Salvage surgery is the sole curative intent treatment option for this course of the disease. The present study evaluates the safety and value of salvage esophagectomy for locoregional failure after high-dose definitive chemoradiotherapy for esophageal squamous cell carcinoma. Methods We reviewed 59 consecutive patients with thoracic esophageal squamous cell carcinoma who underwent salvage esophagectomy after definitive chemoradiotherapy. All patients received more than 60 Gy of radiation plus concurrent chemotherapy for curative intent. The data were compared with those of patients who received esophagectomy without preoperative therapy. Results Postoperative morbidity and mortality rates were increased among patients who underwent salvage esophagectomy compared with those who underwent esophagectomy without preoperative therapy (mean hospital stay, 38 vs 33 days; anastomotic leak rates, 31% vs 25%; respiratory complication rates, 31% vs 20%; reintubation within 1 week, 2% vs 2%; hospital mortality rates, 8% vs 2%). Tracheobronchial necrosis and gastric conduit necrosis were highly lethal complications after salvage esophagectomy; 3-year postoperative survivals were 38% and 58%, respectively. Conclusion Patients who underwent salvage esophagectomy after definitive high-dose chemoradiotherapy had increased morbidity and mortality. Nevertheless, this is acceptable in view of the potential long-term survival after salvage esophagectomy. Such treatment should be considered for carefully selected patients at specialized centers.
We summarize the experience of diagnosis and surgical therapy for primary malignant melanoma of the esophagus (PMME).
Clinical data of 13 patients diagnosed as having PMME treated by surgery as their ...primary therapy from 2000 to 2012 were retrospectively analyzed, and survival information was collected through follow-up.
The average age (±standard deviation) of participants in this study was 66.4±7.6 years, and 84.6% were male. Overall, 61.5% of tumors were located in the lower thoracic esophagus. The accuracies of clinical T stage, N stage, and TNM stage were 53.9%, 46.2%, and 38.5%, respectively, compared with pathological staging (kappa=0.252, p=0.023). Surgical mortality and morbidity were 7.7% and 53.9%, respectively. The incidence of lymph node metastasis for patients with tumor invading within the mucosa was 0, but increased to 42.9% (3 of 7) with tumor invading to the submucosal layer. Primary malignant melanoma of the esophagus in the mid third of the thoracic esophagus had a greater chance to metastasize to perigastric lymph nodes (2 of 5) than to middle mediastinal lymph nodes (1 of 5). For PMME located at the lower third of the thoracic esophagus, upper mediastinal lymph node metastasis was more likely to occur (2 of 4) with tumor invasion penetrating the proper muscle layer. Recurrence occurred within 1 year in all patients with tumor later than Stage Ib. The most common recurrent organ was the liver. The overall 1-year and 5-year postoperative survival rates were 54.0% and 35.9%, respectively, and lymph node metastasis was the independent predictive factor for postoperative survival (p=0.013; odds ratio, 15.05).
Despite the similarity in lymph node metastatic patterns to squamous cell carcinoma, PMME is more inclined to distant metastasis. Clinical staging was inconsistent with pathological staging for PMME based on endoscopy and computed tomography. Surgical therapy was the optimal treatment for PMME at an earlier stage. Early diagnosis and aggressive lymph node dissection were beneficial for accurate staging, potentially reducing recurrence and thus improving survival.
Objectives The objective of this study was to review the prognostic factors for increased survival after salvage esophagectomy after definitive chemoradiotherapy for esophageal squamous carcinoma and ...determine the importance of lymphadenectomy from a prognostic view. Methods Clinical data for all patients from January 1999 to December 2012 who underwent salvage esophagectomy for residual tumor or tumor recurrence after definitive chemoradiotherapy were retrospectively collected. Survival was determined and prognostic factors were analyzed with univariate and multivariate analyses. Results Survival after 1, 3, and 5 years postoperatively was 74.4%, 39.8%, and 29.5%, respectively. The independent predictive factors for increased postoperative survival were tumor recurrence rather than residual tumor as the indication for salvage surgery ( P < .001; odds ratio OR, 0.292); complete tumor resection ( P < .001; OR, 4.520); N category ( P = .089; OR, 1.304); M category ( P = .081; OR, 2.215), and total mediastinal dissection with 15 or more dissected mediastinal lymph nodes ( P = .034; OR, 0.546). Conclusions Salvage indications of recurrence, earlier disease, and complete tumor resection are related to longer survival. The total area of mediastinal dissection with a sufficient number of dissected mediastinal lymph nodes improves survival. Additional neck dissection does not add benefit. The optimal procedure for lymph node dissection in salvage esophagectomy should be established in future studies.
No previous reports on lymph-node metastasis (LNM) from superficial squamous cell carcinoma of the esophagus have proposed definite criteria for additional treatment after endoscopic mucosal ...resection (EMR). We investigated the association between histopathological factors and LNM in 464 consecutive patients with superficial squamous cell carcinoma of the esophagus who had undergone a radical esophagectomy with lymph-node dissection (14 ‘M1' lesions: intraepithelial tumors, 36 ‘M2' lesions: tumors invading the lamina propria, 50 ‘M3' lesions: tumors in contact with or invading the muscularis mucosa, 32 ‘SM1' lesions: tumors invading the most superficial 1/3 of the submucosa and 332 ‘SM2/3' lesions: tumors invading deeper than SM1 level). Histopathological factors including invasion depth, size, lymphatic invasion (LY), venous invasion, tumor differentiation, growth pattern, degree of nuclear atypia and histological grade were assessed for their association with LNM in 82 M3 or SM1 lesions to determine which patients need additional treatment after EMR. LNM was found in 0.0, 5.6, 18.0, 53.1 and 53.9% of the M1, M2, M3, SM1 and SM2/3 lesions, respectively. A univariate analysis showed that each of the following histopathological factors had a significant influence on LNM: invasion depth (M3 vs SM1), LY, venous invasion and histological grade. Invasion depth and LY were significantly associated with LNM in a multivariate analysis. Four out of 38 patients (10.3%) with M3 lesions without LY had LNM, whereas five out of 12 patients (41.7%) with M3 lesions and LY had LNM. Only patients with M1/2 lesions are good candidates for EMR. Invading the muscularis mucosa (M3) is a high-risk condition for LNM the same as submucosal invasion, but M3 lesions without LY can be followed up after EMR without any additional treatment.
Background
Accurate clinical evaluation of lymph nodes is crucial for selection of the optimum treatment strategy for individual esophageal cancer patients. This study investigated the accuracy of ...preoperative clinical diagnosis of lymph node metastasis for patients with clinical stage II/III esophageal squamous cell carcinoma.
Methods
Patients assigned to receive surgery and postoperative chemotherapy in JCOG9907 trial were studied to evaluate the concordance between clinical and pathological nodes. Preoperative diagnosis was based on computed tomography or magnetic resonance imaging.
Results
Among 166 patients in the postoperative group, 160 with sufficient pathological data were studied. The patient background characteristics were: male/female, 147/13; median age, 61 years (range 39–75 years); primary tumor site (upper/middle/lower), 15/76/69; cN0/cN1, 53/107. The sensitivity and specificity of clinical nodes for diagnosis of pathological nodes were 72.7 and 51.3 %, respectively; the positive and negative predictive values were 82.2 and 37.7 %, respectively. The lymph nodes overestimated in the preoperative diagnosis included thoracic paratracheal lymph nodes (#106) (
n
= 8), middle thoracic paraesophageal lymph nodes (#108) (
n
= 4), lymph nodes along the lesser curvature (#3) (
n
= 4), right cardiac lymph nodes (#1) (
n
= 3), and left cardiac lymph nodes (#2) (
n
= 2).
Conclusion
Diagnosis of clinical nodes has low specificity and low negative predictive value for prediction of pathological node category in the preoperative diagnosis of lymph node metastasis for patients with locally advanced resectable esophageal cancer. Clinical staging techniques must therefore be improved for accurate preoperative diagnosis.
Multiple cancers frequently occur in the upper digestive tract. One possible explanation is that specific bacterial infection stimulates the normal epithelium to initiate inflammation and/or promotes ...carcinogenesis. This study was undertaken to determine which bacterial species is predominantly associated with esophageal cancer. We examined the bacterial diversity in this type of cancer and in the saliva from healthy people by using a culture‐independent molecular method. Here we report the preferential and frequent infection of the oral periodontopathic spirochete Treponema denticola (T. denticola), Streptococcus mitis (S. mitis), and Streptococus anginosus (S. anginosus) in esophageal cancer from different regions of the world, and we also describe the induction of inflammatory cytokines by infection of S. anginosus and S. mitis. Our present data suggest that these three bacteria could have significant roles in the carcinogenic process of many cases of esophageal cancer by causing inflammation and by promoting the carcinogenic process, and that eradication of these three bacteria may decrease the risk of recurrence.
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