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Background The clinical outcomes of drug-eluting beads transarterial chemoembolization (DEB-TACE) with doxorubicin-loaded CalliSpheres® beads for patients with unresectable or recurrent esophageal carcinoma have not been reported. The aim of this study is to study the clinical outcomes of DEB-TACE for patients with unresectable or recurrent esophageal carcinoma. Methods This retrospective study enrolled 21 patients (15 men; mean age 68.7 ± 9.7; range 46–86 years) with unresectable or recurrent esophageal carcinoma received DEB-TACE between July 2017 and September 2020. Patient characteristic data, imaging findings, complications and DEB-TACE procedure were reviewed. The primary endpoints, disease control rate (DCR) and objective response rate (ORR), were calculated. The secondary endpoints were overall survival rate and progression-free survival (PFS). Results Twenty-two sessions of DEB-TACE were performed in 21 patients. The technical success rate was 100%; without sever adverse events or procedure-related deaths. All patients received transarterial chemotherapy infusion with raltitrexed or oxaliplatin. The median follow-up period was 3.6 months (interquartile range, IQR 1.5–9.4 months). ORR and DCR were 42.9 and 85.7%, 28.6 and 71.4%, 20.0 and 40.0% respectively at 1-, 3-, and 6-months after DEB-TACE. The median PFS was 6.0 months, and the 3-, 6- and 12-month PFS rates were 68.2%, 45.5 and 0.0%, respectively. The median overall survival was 9.4 months, and the 3-, 6- and 12-month overall survival rates were 75.5%, 55.0 and 13.8%, respectively. Conclusions To our knowledge, this is the first study reports outcomes of DEB-TACE with doxorubicin-loaded CallSpheres bead treatment in the management of patients with unresectable or recurrent esophageal carcinoma. According to our results, this is a safe and feasible treatment modality that may be considered among the options for the treatment of these patients.

Objective The aim of the study was to evaluate diagnostic performance of FDG PET-CT in suspected recurrence of carcinoma esophagus after curative-intent surgical resection and impact of FDG PET-CT on intended management. Material and methods This was retrospective study of patients with clinical or radiological suspicion of recurrent esophageal carcinoma who were referred for PET-CT from January 2006 to December 2017. Diagnostic performance of PET-CT was evaluated for disease recurrence and its impact on management decisions. PET-CT findings were confirmed with tissue diagnosis. When tissue diagnosis was not available clinical and radiological follow-up was used as reference standard. Results Relevant clinical data were available in 68 patients which were considered for analysis. In 91% (62/68) patients FDG PET-CT findings were suggestive of disease recurrence. Histopathological confirmation was available in 43 patients, whereas in remaining patients recurrence was confirmed by radiological and clinical follow-up. Forty percent (28/68) patients were detected with distant metastases. Sensitivity, specificity, positive and negative predictive values of FDG PET-CT was found to be 98.4, 80, 98 and 80% with accuracy of 97%. Change in management was observed in 41% (28/68) of patients from salvage radiotherapy/surgery to palliative chemotherapy/best supportive care based on evidence of distant metastases seen on FDG PET-CT. Conclusion FDG PET-CT is highly sensitive in detection of recurrent disease in esophageal cancer patients after surgical resection. It can detect distant metastases in high proportion of patients thus changing the intent of management from radical salvage to palliative chemotherapy/best supportive care.

Background/aims Endoscopic submucosal dissection (ESD) of recurrent esophageal carcinoma is technically difficult to perform due to submucosal fibrosis that develops after definitive chemoradiation therapy. Therefore, our aim was to evaluate the usefulness of clip-with-thread traction for ESD of esophageal lesions with submucosal fibrosis. Materials and methods Four endoscopists excised 16 lesions by ESD in an ex vivo pig training model. Mock lesions (30 mm in diameter) were created, including a 10-mm area of submucosal fibrosis in the center of each lesion. Each endoscopist performed two ESDs with traction (ESD-T) and two without traction (ESD-N). The primary outcome was the time required for submucosal dissection. Secondary outcomes were the rate of en bloc (complete) resection and perforation during the procedure, and the total amount of solution injected. Results All esophageal ESDs were completed. The median dissection time was significantly shorter for the ESD-T group (median 12.5 min, interquartile range 10.2-14.5) when comparing to the ESD-N group (median 18.0 min, interquartile range 14.6-19.2) (P=0.040). The en bloc resection rate was 100% in both groups, with a rate of complete resection of 87.5% and a rate of perforation of 37.5% for both groups. The median amount of solution injected was not significantly different between the ESD-T (18.0 ml) and ESD-N (20.5 ml) groups (P=0.526). Conclusion Clip-with-thread traction improved the performance of ESD for lesions with submucosal fibrosis. However, the method might not reduce the risk of perforation, which remains an important clinical issue to resolve.

Esophageal carcinoma recurs within two years in approximately half of patients who receive curative treatment and is associated with poor survival. While 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a reliable method of detecting recurrent esophageal carcinoma, in most previous studies FDG PET/CT scans were performed when recurrence was suspected. The aim of this study was to evaluate FDG PET/CT as a surveillance modality to detect recurrence of esophageal carcinoma after curative treatment where clinical indications of recurrent disease are absent. A total of 782 consecutive FDG PET/CT studies from 375 patients with esophageal carcinoma after definitive treatment were reviewed. Abnormal lesions suggestive of recurrence on PET/CT scans were then evaluated. Recurrence was determined by pathologic confirmation or other clinical evidence within two months of the scan. If no clinical evidence for recurrence was found at least 6 months after the scan, the case was considered a true negative for recurrence. The diagnostic sensitivity and specificity of PET/CT for detecting recurrent esophageal carcinomas were 100% (64/64) and 94.0% (675/718), respectively. There were no significant differences in the diagnostic performance of PET/CT for detecting recurrence according to initial stage or time between PET/CT and curative treatments. Unexpected second primary cancers were detected by FDG PET/CT in seven patients. Surveillance FDG PET/CT is a useful imaging tool for detection of early recurrence or clinically unsuspected early second primary cancer in patients with curatively treated esophageal carcinoma but without clinical suspicion of recurrence.

Background Recurrent esophageal carcinoma (EC) has a dismal prognosis. However, prior studies showed that selected patients with isolated recurrence may benefit from definitive therapy. The aim of this study was to identify the predictors of postrecurrence survival (PRS) in patients with isolated EC recurrence who were treated with curative intent. Methods A retrospective review of a prospective database (1988 to 2015) was performed to identify all recurrent EC patients after curative esophagectomy. Demographic and clinicopathologic data were reviewed. The probability of PRS was estimated with the Kaplan-Meier method. Predictors of PRS after definitive therapy for isolated EC recurrence were determined by the multivariable Cox proportional hazards model. Results Of the 640 curative esophagectomies, 241 patients (37.7%) experienced recurrences (median follow-up 50 months). Fifty-six patients (9%) received definitive treatment of isolated EC recurrence (31 were treated surgically with or without chemotherapy-radiotherapy [CTRT] and 25 received definitive CTRT alone). Median time to recurrence (TTR) was 19 months. The 1- and 3-year PRSs were 78% and 38% (median survival 26 months). On multivariable analysis; TTR was the only significant independent predictor for survival after recurrence (hazards ratio 0.98, 95% confidence interval: 0.96 to 0.99, p = 0.034). No pronounced difference was found in disease-free survival or in PRS between recurrent patients treated with operation with or without CTRT and patients who received definitive CTRT. Conclusions A select subgroup of patients with isolated EC recurrence can be treated with curative intent. TTR was the best predictor for PRS.

There is currently no consensus on salvage therapy for recurrent esophageal cancer. Salvage surgery is a well-established option for attaining long-term survival; however, it is associated with a high risk of perioperative morbidity and mortality. A total of 6 patients who underwent re-irradiation for recurrence of locoregional esophageal cancer following definitive chemoradiotherapy were investigated. The median interval between initial radiotherapy and re-irradiation was 17.4 months (range, 6.4–59.2 months). Re-irradiation salvage therapy was mostly administered with concurrent chemotherapy, which consisted of several cycles of nedaplatin on day 1 and oral S-1 administration on days 1–14. The median survival after re-irradiation was 13.6 months (range, 1.9–33.3 months). A total of 3 patients who completed hyperfractionated radiation therapy survived for >1 year. One patient has had no signs of recurrence or late radiation toxicity for >2 years. Severe acute hematological adverse events (AEs) occurred in 3 patients, including 1 case of grade 4 leukopenia. One severe late AE occurred in 1 patient, who developed grade 3 dysphagia and became permanently dependent on percutaneous endoscopic gastrostomy tube feeding. Salvage radiotherapy is considered to be a good treatment option for inoperable locoregional recurrent esophageal cancer. The results of the present study demonstrated that re-irradiation, with or without chemotherapy, for recurrent esophageal carcinoma after definitive chemoradiotherapy was tolerable and yielded reasonably satisfactory results.

// Peipei Wu 1, 2, * , Jing Liu 1, * , Xiaorong Sun 3 , Xiaolin Li 1 , Ligang Xing 1 and Jinming Yu 1 1 Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medicine Science, Jinan 250117, Shandong, China 2 Department of Oncology, Jining No.1 People’s Hospital, Jining 272011, Shandong, China 3 Department of Radiology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medicine Science, Jinan 250117, Shandong, China * These authors have contributed equally to this work Correspondence to: Ligang Xing, email: xinglg@medmail.com.cn Keywords: esophageal cancer, sodium glycididazole, radiosensitizer, tumor bed effect, hypoxia Received: December 15, 2016 Accepted: June 05, 2017 Published: July 10, 2017 ABSTRACT Re-irradiation is challenging for esophageal cancer patients with local-regional recurrence after initial radiotherapy. The purpose of this study is to establish a recurrent esophageal tumor model and investigate radiosensitizing effects of sodium glycididazole (CMNa). Tumor models were established by pre-irradiation (0 Gy, 10 Gy or 20 Gy) to the right hind leg of the nude mice 24 hours before tumor transplantation (ECA109 human esophageal carcinoma cells). Tumor growth curves were analyzed. Hypoxic microenvironment was exhibited in tumor frozen slides stained for pimonidazole, Hoechst 33342, hematoxylin-eosin and CD34. Mice bearing primary (0 Gy pre-irradiation) and recurrent (10 Gy pre-irradiation) tumors were randomized into control (no treatment), radiation (30 Gy in 3 weekly fractionations), or radiation combined with CMNa (1 mmol/kg i.p. injected 60 min before radiation) respectively. The data showed tumors from 10 Gy and 20 Gy pre-irradiated sites grew significantly slower than those in the 0 Gy pre-irradiated group. The recurrent xenograft tumors showed increased necrotic fractions, decreased micro-vascular density, increased pimonidazole-positive fraction, and decreased Hoechst-positive fraction. In the primary xenograft tumors, CMNa adding to radiation did not lead to significant tumor growth delay than radiation alone. However, for the recurrent tumor model, the growth rate was remarkably reduced as CMNa combined with radiation as comparison with radiation alone. In conclusion, the recurrent esophageal xenograft model with tumor bed effect was successfully established characterized by slow growth, increased hypoxia fraction and decreased blood flow. Significant radiosensitization by CMNa was demonstrated in the recurrent model.

Local tumor recurrence is one of the main causes for the failure of esophageal cancer treatment following radiotherapy. Previous studies have demonstrated that epidermal growth factor receptor (EGFR)‑targeted therapy combined with radiotherapy is expected to become an effective means to control tumor recurrence. The aim of the present study was to investigate the effect and mechanism of nimotuzumab (an EGFR‑targeted antibody) in the treatment of recurrent esophageal carcinoma. The radiation responses of two esophageal squamous carcinoma cell lines, EC109 and TE‑1, with or without nimotuzumab, were first evaluated by CCK‑8 assay. Colony formation and apoptosis were used to measure anti‑proliferation effects. It was demonstrated that nimotuzumab arrested the cell cycle at the G2 phase in vitro. Western blotting and immunofluorescence analysis were used to determine signaling pathway changes. It was observed that nimotuzumab inhibited phosphorylation of EGFR in EC109 cells. Furthermore, recurrent tumor models were established and it was identified that the degree of tumor hypoxia was positively associated with EGFR overexpression. In EC109 cell xenografts, nimotuzumab combined with radiation led to a significant delay in recurrent tumor growth compared with that of radiation alone (P

Background Strategies for the treatment of recurrence after initial curative esophagectomy are increasingly being recognized. The aim of this study was to identify prognostic factors that affect survival in patients with recurrence and to evaluate treatment strategies. Methods A prospective database (2003–2013) was used to collect consecutive patients with esophageal carcinoma treated with initial curative esophagectomy. Locations, symptoms, and treatment of recurrence were registered. Post-recurrence survival was defined as the time between the first recurrence and death or last follow-up. Results Of the 335 selected patients, 171 (51 %) developed recurrence. Multivariable analysis identified distant recurrence as opposed to locoregional recurrence [hazard ratio (HR) 2.15, 95 % confidence interval (CI) 1.27–3.65; p = 0.005], more than three recurrent locations (HR 2.42, 95 % CI 1.34–4.34; p = 0.003), and treatment (HR 0.29, 95 % CI 0.20–0.44; p

Item does not contain fulltext BACKGROUND: Numerous patients will develop recurrent disease after esophagectomy for esophageal carcinoma (EC). In literature, survival after recurrent EC is poor with 6-8 months. In these studies, diagnostic imaging during follow-up (FU) is routinely performed. In the Netherlands, routine imaging is not part of FU and only performed on indication. The aim of this study was to determine survival after diagnosis of recurrent disease in patients after esophagectomy without routine imaging during FU. METHODS: All EC patients who underwent esophagectomy between 1993 and 2010 were included and followed for clinical evidence of recurrent EC. Location, symptoms, diagnosis, and treatment of recurrent disease were registered. Pattern of recurrence was compared between patients who underwent neoadjuvant therapy and patients who underwent surgery alone. Survival after detection of recurrence was determined in all patients and related to the year of surgery. RESULTS: A total of 493 of 1,088 patients (45 %) who underwent esophagectomy between 1993 and 2010 developed recurrent disease. Median interval between esophagectomy and recurrence was 10.5 months. Within the first 2 years after surgery, 33 % of patients developed recurrent EC. The majority of patients (51 %) were diagnosed with distant metastases. Locoregional recurrence occurred significantly less often among patients who underwent neoadjuvant therapy (6 vs 16 %, p = .017). Median survival after diagnosis of recurrent disease was 3 months. No relation was observed between the year of surgery and survival after recurrent disease (p = .931). CONCLUSIONS: Survival after recurrent EC in patients who undergo FU without routine imaging after esophagectomy is approximately 3 months and has not improved over the past 18 years. 01 augustus 2013

SUMMARY The efficacy of using self-expanding metallic stent (SEMS) for palliation of symptoms because of tumor recurrence after prior esophagogastrectomy has not been properly assessed despite the well recognized use of SEMS in patients without prior surgery. The aim of this study is to evaluate the efficacy and safety of using SEMS in patients who had prior esophagogastrectomy. The study group included 35 patients with carcinoma of esophagus or cardia documented to have loco-regional recurrence after esophagogastrectomy and in whom SEMS were placed for palliation. The median age was 67 (ranged 41–85). The indications for stenting were dysphagia caused by recurrence at the esophageal anastomosis (n= 4) and in the esophageal remnant (n= 5), or extrinsic compression from mediastinal nodal disease (n= 7); gastric outlet obstruction produced by extrinsic tumor compression (n= 13); and tracheo-esophageal fistulae (n= 6). Forty-three stenting procedures were performed, and the technical success rate was 97.6%. The dysphagia score improved from 4.66 to 2.54 (P < 0.001). All patients with tracheo-esophageal fistula had their symptoms successfully palliated. The immediate complication rate was 14% (n= 5); two patients had stent malpositioning, two had inadequate opening of their stents, and one had a failed stenting procedure. On follow-up, 15 (42.8%) patients required a total of 22 re-intervention procedures for various reasons: endoscopic dilatation (five dilatations in three patients), removal of foreign bodies (nine procedures in four patients), and insertion of a second SEMS related to tumor growth (eight stents in eight patients). There was no procedure-related mortality. The median survival was short at 42 days (range 5–290 days), mostly related to advanced disease stage. SEMS in patients with recurrent tumor after esophagogastrectomy is safe and effective.

Salvage surgery is one important therapeutic option after locoregional failure of definitive chemoradiotherapy (dCRT) in patients with advanced or recurrent esophageal carcinoma. We have performed cervical lymph node dissection as a salvage surgery after chemoradiotherapy in a patient with recurrent esophageal carcinoma. A 54-year-old Japanese man was admitted to our hospital because of multiple lymph node metastases after endoscopic submucosal dissection (ESD) for early-stage esophageal carcinoma. The patient underwent a circumferential ESD of early-stage esophageal carcinoma in another hospital. The esophageal carcinoma, measuring 75 × 60 mm in size, was a superficial spreading type located in the middle portion of the thoracic esophagus. Histology of the resected specimen revealed a moderately to poorly differentiated squamous cell carcinoma, and the depth of invasion was limited within the mucosal layer associated with a small area being attached to the muscularis mucosae. Five months after ESD, lymph node metastases in the regions of right recurrent nerve and the left tracheobronchus were found, for which dCRT was performed. These metastatic lymph nodes disappeared in the chest CT scan images. Lymph node metastasis in the region of the right recurrent nerve then reappeared 8 months after the completion of CRT. Considering the solitary lymph node metastasis and surgical invasiveness, lymph node dissection using a cervical approach was selected as a salvage surgery. Cervical approach for the lymph node dissection in the region of right recurrent nerve may be one feasible option as a minimally invasive salvage surgery for patients with recurrent esophageal carcinoma after dCRT.

Background Limited locally recurrent esophageal carcinoma is rare, and little is known regarding effectiveness of re-resection. Methods Medical records of 27 consecutive patients with locally recurrent esophageal carcinoma who underwent reoperation at our institution between February 1974 and January 2003 were analyzed. Results The original and recurrent cancer cell types were identical in all patients. Median disease-free interval was 19.4 months (range, 2.5 to 170 months). Recurrence was at the anastomosis in 23 patients (85%), esophageal remnant in 3 (11%), and stomach in 1 (4%). Ten patients had completion gastrectomy and partial esophagectomy, and 9 had resection of the anastomosis. The remaining 8 patients were found intraoperatively to have unresectable disease and underwent biopsy only. Re-resection was complete in 15 of the 19 patients resected (79%). Four patients had microscopic cancer at the resection margins. Reconstruction was with colon in 10 patients and esophagogastrostomy in 9. There were 2 deaths (operative mortality, 7%). Complications occurred in 16 patients (59%). Arrhythmia and anastomotic leak were the most common complications and each occurred in 7 patients (26%). Factors favorably associated with survival were disease-free interval greater than 2 years ( p ≤ 0.05) and complete re-resection ( p ≤ 0.02). Two-, three-, and five-year survival for patients completely re-resected was 62%, 44%, and 35%, respectively. Survival for patients who had incomplete re-resections was 18% at 2 years and zero at 3 years. Conclusions Re-resection of locally recurrent esophageal carcinoma is associated with considerable morbidity. However, long-term survival is possible in patients with a long disease-free interval or a complete re-resection.

Purpose: The aim was to assess the improvement in swallowing status, complication rate, and overall survival. Patients and Methods: Fifty-eight patients with advanced/recurrent esophageal carcinoma were treated for palliation with high-dose-rate intraluminal brachytherapy (HDR-ILRT) with a remote afterloading microSelectron unit (192Ir source) with or without external radiation from November 1994 to May 2000 at the Tata Memorial Hospital. The mean age was 64 years. The mid-third of the esophagus was involved in 38 patients (66%). The group was comprised of 37 previously untreated patients (29 with ≤50% Karnofsky performance status and old age, 4 with metastatic disease, and 4 with second primary esophageal lesions) and 21 patients with post-treatment recurrent tumors. Thirty-eight patients (65%) received intraluminal brachytherapy alone, whereas the remaining 20 patients (35%) received a combination of external and intraluminal radiation therapy. All patients received 2 fractions of HDR-ILRT 1 week apart with 600 cGy per fraction at 1 cm off axis. Results: Overall improvement in swallowing status was seen in 22 patients (48%), and 24 (41%) maintained pretreatment swallowing status. Median dysphagia-free survival was 10 months. Overall complication rates were 30%, with stricture seen in 9 patients (15%), ulceration in 6 (10%), and tracheo-esophageal fistula in 3 patients (5%). Complication rates were higher in the post-treatment group (38%) than in the previously untreated group (27%) (p = 0.29). The median overall survival for the entire group was 7 months. Median survival was better, although not significantly, for the previously untreated cohort: 7.8 months vs. 6 months for the post-treatment group (p = 0.77). Conclusion: HDR-ILRT brachytherapy achieves good palliation with acceptable complications in advanced/recurrent esophageal carcinoma.

Purpose: To assess the clinical efficacy and side effects of radiotherapy combined with sodium glycididazole in the treatment of recurrent esophageal carcinoma.Methods: Ninety patients with locally recurrent oesophageal carcinoma who were admitted to the Oncology Department at Taian City Central Hospital, Shandong, China, were randomly divided into a treatment group (treated with radiotherapy and sodium glycididazole) and a control group (treated with radiotherapy alone) in a randomized study. Short-term curative effects, median progression-free survival (PFS), and side effects were compared between the two groups.Results: The cure rate in the treatment group was 86.70 %, whereas that in the control group was 51.10 % (p < 0.05). Median PFS in the treatment group was 9.9 months versus 5.3 months in the control group (p < 0.05). Side effects in both groups included alopecia, headache, nausea, vomiting and leucopaenia, at level one or two. In this regard, the difference between the two groups was statistically insignificant (p > 0.05).Conclusion: Radiotherapy combined with sodium glycididazole shows a higher short-term curative effect in the treatment of recurrent oesophageal carcinoma than radiotherapy alone.Keywords: Alopecia, Leucopaenia, Oesophageal carcinoma, Radiotherapy, Sodium glycididazole

The mortality rate of recurrent esophageal carcinoma remains high because of its resistance to chemotherapy and radiation therapy. We present a patient with recurrent esophageal carcinoma, which dramatically disappeared after treatment with the combination of continuous infusion of 5-fluorouracil and low-dose cis-Diamminedichloroplatinum-II (cisplatin) infusion (FP therapy). Furthermore, we immunohistologically found that glutathione S-transferases (GST)-pi, a marker of resistance to cisplatin, was faintly expressed both in the endoscopical biopsy specimens of recurrent tumor and in the resected specimens of esophageal carcinoma and metastatic lymph nodes. FP therapy was suggested to be effective for recurrent esophageal carcinoma. Immunostaining for GST-pi might be a prospective marker for the sensitivity of esophageal carcinoma to FP therapy, particularly cisplatin.

We inserted Dumon stent to 13 patients with tracheobronchial stenosis due to advanced or recurrent esophageal carcinoma. Severe dyspnea was improved in 11 patients except for 2 patients with bilateral recurrent nerve palsy. 3 cases who had radiation therapy or chemotherapy lived over 150 days. We inserted esophageal stent in 4 cases. 2 patients died due to hemoptysis after 156 days and 35 days. We conclude that Dumon stent is one of the useful treatments in order to improve quality of life and prognosis of advanced or recurrent esophageal carcinoma.

Dysphagia is an important and distressing symptom which has a significant impact on the quality of life of patients with carcinoma of the esophagus. Although endoscopic palliation of dysphagia due to unresectable or recurrent esophageal carcinoma can be provided by esophageal dilatation and intubation, laser ablation, injection of alcohol or sclerosants, or brachytherapy, these techniques are often unsuitable for the palliation of high esophageal tumors. We present a patient with recurrent carcinoma of the proximal esophagus who developed an inability to swallow as a complication of intubation with an esophageal stent. The dysphagia improved dramatically after the stent was removed.

Prognosis of inoperable or recurrent esophageal carcinoma is, at best, poor. Once an esophagotracheal fistula has developed, the overall condition of the patient declines rapidly. Aspiration pneumonia and severe coughing are common. The introduction of esophageal tubes does not always seal the fistula sufficiently and may compromise the airway causing stridor and dyspnea. In 30 patients (25 male, 5 female; age 23 to 74 years; mean, 56 years) with very large fistulas and airway problems, we inserted an airway stent (Dynamic) (n = 12) or an esophageal tube combined with a Dynamic airway stent (n = 18) with the aim of sealing the fistula and restoring patency of the airway and GI passage. The tracheobronchial Dynamic stent was chosen because its slightly concave, flexible posterior silicone membrane adapts ideally to the convex esophageal tube. The stents were well tolerated and significantly improved the quality of life. Of 30 patients, 16 could breathe and swallow unimpaired until shortly before their death. Moderate complaints persisted in five patients, dysphagia in eight patients, and dyspnea in one patient. Mean survival time in the double stent group was significantly greater (110 days) than in the airway stent-only group (24 days) or comparable groups in the literature treated with esophageal tubes only. We conclude that carefully selected patients can benefit from double stenting of esophagus and airways.

To evaluate the effect of the extended lymphadenectomy for thoracic esophageal carcinoma, the pattern of recurrence in the 50 patients with pT3 tumors who underwent esophagectomy with cervical, mediastinal, and abdominal lymph node dissection (3-F) (group A) was compared with that of 100 patients at pT3 who underwent esophagectomy without upper mediastinal and cervical lymphadenectomy (2-F) (group B). The cumulative 5-year survival rate for 115 patients who underwent 3-F was 50.9%. Cumulative 5-year survival rates for patients in groups A and B were 36.8% and 22.0%, respectively. The survival curve for group A was significantly better than group B (P = 0.02332). Lymphatic recurrence was noted less frequently in group A (8/23) than in group B (31/49) (χ2 = 5.1149), whereas the rate of hematogenous recurrence was similar. Extension of the field of lymph node dissection reduced the lymph node recurrence in patients with thoracic esophageal carcinoma, which may have positively affected patient survival. © 1996 Wiley-Liss, Inc.

The feasibility and effectiveness of radiotherapy in the management of recurrent esophageal carcinoma (REC) is reported. A consecutive cohort of 54 patients with rcT1-4, rcN0-1, or cM0 recurrent esophageal carcinoma (69% squamous cell carcinoma, 31% adenocarcinoma) was treated between 1988 and 2010. The initial treatment for these patients was definitive radiochemotherapy, surgery alone, or neoadjuvant radiochemotherapy + surgical resection in 8 (15%), 33 (61%), and 13 (24%) patients, respectively. The median time to recurrence from initial treatment was 19 months (range 4–79 months). The site of the recurrence was anastomotic or local, nodal, or both in 63%, 30%, and 7% of patients, respectively. Salvage radio(chemo)therapy was carried out with a median dose of 45 Gy (range 30–68 Gy). Median follow-up time for surviving patients from the start of R(C)T was 38 months (range 10–105 months). Relief of symptoms was achieved in 19 of 28 symptomatic patients (68%). The median survival time was 12 months (95% confidence interval (CI) 7–17 months) and the median recurrence-free interval was 8 months (95% CI 4–12 months). The survival rates at 1, 2, and 3 years were 55 ± 7%, 29 ± 6%, and 19 ± 5%, respectively. The recurrence-free survival rates at 1, 2, and 3 years were 44 ± 7%, 22 ± 6%, and 15 ± 5%, respectively. A radiation dose ≥ 45 Gy and conformal RT were associated with a better prognosis. RT is feasible and effective in the management of recurrent esophageal carcinoma, especially for relief of symptoms. Toxicity is in an acceptable range. The outcome of REC is poor; however, long-term survival of patients with recurrent esophageal carcinoma after radiochemotherpy might be possible, even with a previous history of radiotherapy in the initial treatment. If re-irradiation of esophageal carcinoma is contemplated, three-dimensional conformal techniques and a minimum total dose of 45 Gy are recommended.

Computed tomographic (CT) scans were retrospectively reviewed for evidence of (a) intragastric soft-tissue mass or gastric wall thickening, (b) extragastric soft-tissue mass or mediastinal lymph node enlargement (local-regional disease), (c) abdominal lymph node enlargement, and (d) metastatic disease to distant organs.Fifty-eight patients with a clinical suspicion of recurrent esophageal carcinoma underwent CT. The thoracic level of local-regional recurrence was compared with the level of the primary tumor.Proof of recurrence status was obtained in 52 of 58 patients. Of the 58 patients, 36 (62%) had CT findings of recurrence, 16 (28%) had no CT findings of recurrence, and six (10%) had CT findings questionable for recurrence. CT accuracy for determining recurrence status was 87%. There was no correlation between the level of primary tumor and that of recurrence.At CT, tumor recurrences were most commonly seen as some combination of local-regional disease, distant metastases, and abdominal lymph node enlargement. CT findings isolated to one region were seen only occasionally.

われわれは胸部食道癌切除後6年3か月経過して発見された遺残食道再発と思われる1例を経験したので報告する.症例は52歳男性で, 6年3か月前に当科にて胸部食道癌に対して右開胸.開腹胸部食道全摘, 胸壁前食道胃吻合を施行されている.術後経過は良好であり, 近医にて経過観察されていたが, 再び嚥下困難が生じるようになった.上部消化管造影および内視鏡検査にて吻合部付近の狭窄が指摘され, 精査目的で当科再入院となった.前回の摘出標本の病理組織学的検討より遺残食道再発と思われた.頸部食道切除および胃管上部部分切除, 両側頸部郭清を行い, 手術用顕微鏡を用いた血管吻合法を併用して遊離空腸を用いて再建した.術後経過は良好で, 再手術後4年経過したが再発の兆候を認めていない.

The aim of this study was to evaluate the efficacy and complications of self-expandable metallic stent placement for patients with inoperable esophageal carcinoma after radiotherapy and/or chemotherapy. We obtained data from 19 patients with advanced or recurrent esophageal carcinoma between 1996 and 2000. In all patients, a self-expandable metallic stent was placed under fluoroscopic guidance. Dysphagia before and after stent placement was graded. Complications after stent placement were also evaluated. Data were compared between patients with and without prior radiotherapy and/or chemotherapy. The procedure was technically successful in all but one patient. The dysphagia grade improved in all patients. No life-threatening complications occurred. The other major complications such as mediastinitis occurred in two patients, and pneumonia and funnel phenomenon occurred in one patient each. These patients had a history of radiotherapy and/or chemotherapy prior to stent placement. Eight of the twelve patients with prior radiotherapy and/or chemotherapy compared with one of seven patients without prior therapy had persistent chest pain, which was a statistically significant difference (P < 0.05). Placement of self-expandable metallic stents was effective for patients with advanced or recurrent esophageal carcinoma. However, prior irradiation and/or chemotherapy increased the risk of persistent chest pain after stent placement.

Despite an increase in radical surgery for esophageal carcinoma, many patients continue to develop recurrent disease. Some reports have suggested that recurrent tumors should be treated aggressively with a combination of chemotherapy and radiotherapy. The aim of this study was to assess the comparative utility of computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of recurrence after curative resection of cancer of the esophagus and gastroesophageal junction. To maximize survival benefit, detection of tumor recurrence as early and accurately as possible is important. Twenty-three patients who developed recurrent tumors after curative transthoracic esophagogastrectomy for esophageal carcinoma were analyzed retrospectively. The CT and MRI findings were correlated with pathology or with endoscopic and clinical follow-up. Primary tumor recurrence was detected at the anastomosis side in 19 patients (intraluminal mass in 13 and as diffuse or focal wall thickening in six). Distant recurrence was seen in the liver (n = 5), lung (n = 4), bone (n = 3), abdominal lymph node (n = 4), pleural effusion (n = 2) and pericardial effusion (n = 1). CT and MRI were found equal in showing the intraluminal mass, liver metastasis, pleural and pericardial effusion. Thickening of esophageal wall was demonstrated in nine patients using CT, but only seven of these tumor recurrences were confirmed by MRI, the remaining two were related to secondary fibrosis. Both CT and MRI showed diffuse gastric wall thickening determined as false tumor recurrence due to severe gastritis in one case. There were two (50%) false negatives for lung metastasis in MRI and one bone metastasis (33%) false negative in CT. CT was found superior in the demonstration of lung metastasis and MRI was superior in the evaluation of wall thickening and bone metastasis.

Purpose: Experimental data, both in vivo and in vitro, suggest that the combination of gemcitabine and cisplatin acts synergistically. Within the Southwest Oncology Group, we designed a Phase II trial to test this chemotherapy combination for patients with esophageal cancer. Experimental design: Patients with metastatic or recurrent esophageal cancer were treated with gemcitabine 1000 mg/m2 on days 1, 8, and 15, and cisplatin 100 mg/m2 on day 15. Cycles were repeated every 28 days. The statistical endpoint was overall survival. Results: Sixty-four eligible patients were accrued from 37 institutions. Twenty-six percent of patients had prior chemotherapy. The treatment was generally well-tolerated, with the most common toxicity being neutropenia in 31% of patients. All 64 patients have died. Survival at 3 months was 81%, and at 1 year was 20%. Median survival was 7.3 months. Conclusions: This regimen is tolerable palliative option for patients with metastatic esophageal cancer.

Cancer cells that survive fractionated irradiation can be radioresistant and cause tumor recurrence. However, the molecular mechanisms underlying the development of radioresistance in cancer cells remain elusive. The aim of this study was to investigate the role of WISP-1 in the development of radioresistance in esophageal carcinoma during fractionated irradiation. Radioresistant esophageal cancer cells were generated from normal esophageal cancer cells via fractionated irradiation, and expression levels of related proteins were determined by Western blot. Radiosensitivity of cells was established by clonogenic cell survival assays, and cell cycle distribution was evaluated by flow cytometry. Protein distributions were determined by immunofluorescence, and cell toxicity was evaluated by cell counting kit-8 assays. In vivo validations were performed in a xenograft transplantation mouse model. Our data indicate that WISP-1 plays an important role in the development of radioresistance in esophageal cancer cells during fractionated irradiation. The overexression of WISP-1 in esophageal cancer cells was associated with radioresistance. Depletion of extracellular WISP-1 by antibody neutralizing reversed radioresistance and directly induced mitotic catastrophe resulting in cell death. WISP-1 may be a candidate therapeutic target in the treatment of recurrent esophageal carcinoma after radiotherapy.

Background Recent advances in chemoradiotherapy for esophageal carcinoma have resulted in improved survival rates. However, there are few options for recurrent dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy. The aim of this study was to evaluate the safety and efficacy of self-expandable metallic stent placement for patients with recurrent esophageal carcinoma where definitive chemoradiotherapy has failed. Methods Thirteen consecutive patients with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable metallic stents were placed after failure of primary chemoradiotherapy, were studied retrospectively. All patients had esophageal obstruction or malignant fistula. Results The oral alimentation status of nine of 13 patients (69%) improved after successful placement of the stent. Following placement of the stent, fever (>38 degrees C) and severe chest pain occurred in 85% (11/13) of the patients. In all patients examined, C-reactive protein was elevated within 1 week of the operation. Esophageal perforation occurred in three patients. Stent-related mediastinitis and pneumonia developed in six (46%) and three (23%) patients, respectively. Seven of the 13 patients (54%) died of stent-related pulmonary complications. Conclusion Although the placement of a self-expandable metallic stent for patients with recurrent esophageal carcinoma after failure of chemoradiotherapy improved their oral alimentation status, we found that this treatment increases the risk of life-threatening pulmonary complications.

We treated a complete obstruction of the left mainstem bronchus due to nonresectable recurrent esophageal carcinoma with a combination of laser therapy, radiation therapy, and the placement of an expandable metallic stent. The patient survived 1 year after the first therapy, with good quality of life. We conclude that a combination of laser ablation, radiotherapy, and stent placement can improve survival and quality of life for the patients with complete malignant bronchial obstruction.

Purpose/Objectives: Patients with locally advanced esophageal carcinoma are recommended to undergo treatment with radiation and chemotherapy, which may be followed by surgery in appropriate operative candidates. Radiation has traditionally been delivered with 3D conformal radiation therapy (3D CRT). This study is evaluating early outcomes and acute and late toxicity in patients treated with Intensity Modulated Radiation Therapy (IMRT) with concurrent chemotherapy. Materials/Methods: This is a retrospective review of 17 patients with esophageal carcinoma treated with IMRT and chemotherapy from 2008 2010. Pathology includes squamous cell and adenocarcinomas. Tumor sites include middle thoracic, lower thoracic and GE junction. Initial clinical stages are TX-T3, N0-3, and M0-1. All patients received at least one cycle of concurrent 5-fluorouracil with either cisplatin or oxaliplatin. IMRT dose was 50.4 Gy in 28 fractions prescribed to a target volume which included the tumor and regional lymphatics. All IMRT plans utilized coplanar beams in a 7-9 beam arrangement. Results: Median follow-up is 9 months (range, 4-20). Median patient age is 72 (range, 55-87). Sixteen patients received 50.4 Gy via an IMRT plan, and one received 25.2 Gy. Trimodality treatment was completed in 11 patients (65%). Surgery was either esophagogastrectomy or minimally invasive esophagectomy. Of the 11 patients who proceeded to surgery, 3 (27%) had a pathologic complete response, 7 (64%) had a partial response (PR) and 1 patient (9%) had stable disease. Of the 6 patients who received chemotherapy and IMRT alone, 2 patients had a clinical PR, 1 had disease progression, and 3 did not have follow-up data available. In the initial 17 patients, there were no local or regional recurrences, though 2 patients developed distant metastases. Twelve patients are alive at last follow-up. Of the 5 deaths, 2 were due to esophageal cancer, 1 from radiation complications, 1 from chemotherapy complications, and 1 from surgical complications. Acute CTCAE V4.0 grade 3 toxicities from concurrent chemotherapy and IMRT developed in the following patients: 2 esophagitis, 1 fatigue, 1 nausea/vomiting, 4 dehydration, 1 anemia, 1 thrombocytopenia and 5 neutropenia. Patients with grade 4 toxicities included 1 thrombocytopenia and 1 neutropenia. Four patients developed late grade 3 esophageal strictures. There was one grade 4 cardiac complication, and one grade 5 pleuro-esophageal fistula. There were no cases of radiation pneumonitis or ulcers. Conclusions: IMRT is a feasible treatment modality, which may be equally efficacious to 3D CRT for the treatment of esophageal carcinoma, and may offer fewer treatment complications, including a lower incidence of pneumonitis. Author Disclosure: K.V. Kowalchik: None. G. Kim: None. E. Johnson: None. N. Paryani: None. S. Ko: None.

Biopsy tissue from a 72-year-old Japanese woman with metastasis to the cervical lymph nodes of recurrent esophageal carcinoma was adapted for culturing on the surface of lethally X-irradiated confluent monolayers of Balb/c 3T3 cells, and a continuous-growing tumor cell line was developed. These cells were found to contain keratinous material by immunohistochemical staining. We confirmed that these cells were of human origin by performing chromosome analysis. Thus, this line, designated as KSE-2 line, was considered to have originated from metastatic squamous-cell carcinoma of the human esophagus. When the attachment and growth of KSE-2 was examined on various culture surfaces, the confluent monolayers of Balb/c 3T3 cells were found to be more suitable than other substrata, such as plastic and collagen-coated dishes. The fixation of confluent monolayers of 3T3 cells with 3% glutaraldehyde had almost no affect on the colony-forming efficiency of the KSE-2 cells. In addition, the period of lag phase after inoculation of KSE-2 cells on fixed as well as nonfixed monolayers was shorter than that on plastic dishes. The conditioned medium from lethally X-irradiated 3T3 cells did not enhance the attachment and proliferation of KSE-2 cells on both nonfixed and fixed confluent monolayers. From these results, the surface structure itself of the 3T3 confluent monolayer was considered to play an important role in the favorable attachment and proliferation of KSE-2 cells.

The posterior tracheal band (PTB) was studied on upright chest radiographs in 43 patients and its appearance and diagnostic usefulness correlated with recurrence of esophageal carcinoma after surgery of radiation therapy. It was seen well enough to be useful in 36 treated patients (83.7%). In 10 of 17 recurrent carcinomas (60%), all or part of the PTB showed progressive thickening up to greater than or equal to 5 mm compared with radiographs taken one month after therapy or later, suggesting recurrence in 6 of 8 cases after resection and in all 4 cases after radiotherapy. Such thickening never occurred in patients without recurrent carcinoma. In 6 of 10 cases, thickening of the PTB preceded the diagnosis of recurrence by two to six months.

In a Phase II study, patients with measurable metastatic or recurrent esophageal carcinoma randomly received after Adriamycin (ADR), 60 mg/M2 I.V. q three weeks, or methotrexate (MTX), 40 mg/M2 I.V. q one week, or 5-fluorouracil (5-FU), 500 mg/m2 I.V. x 5 days q five weeks. Objective partial response rates for 72 patients were 5% for ADR (one of 20), 12% for MTX (three of 26), and 15% for 5-FU (four of 26). There were no complete responses. Median duration of response was 13 weeks. Median survival was 14 weeks (eight weeks for ADR, 14 weeks for MTX, and 15 weeks for 5-FU). Factors of liver metastasis, adjacent anatomic involvement, time from initial diagnosis to study entry, and prior radiation were found to be significant determinants of survival. Adriamycin did not appear to benefit patients with advanced measurable squamous cell carcinoma of the esophagus. Methotrexate and 5-fluorouracil showed comparable activity and survival, although methotrexate was slightly more toxic.

The introduction of any new technique in medicine requires verification of variations of the normal appearance that may simulate disease. The subsequent case of CT of the chest demonstrates a patient with known carcinoma of the esophagus treated with external radiation therapy. A CT chest examination for evaluation of possible recurrent disease was performed 1.5 years after the therapy. This report demonstrates a spurious interpretation of CT of the chest for recurrent esophageal carcinoma.

Three cases of surgical implantation of esophageal carcinoma during esophagogastrectomy are presented. The CT and radiographic appearance is demonstrated. A possible etiology and method for decreasing the risk of surgical spread of tumor are discussed.

Nine long-term survivors of carcinoma of the esophagus treated with preoperative x-ray therapy were assessed. Eight lived or are living more than five years after treatment. One was lost to follow-up. None has had recurrent esophageal carcinoma. In view of these findings, the authors recommend preoperative radiotherapy for esophageal cancer.