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1.

Background

The increasing prevalence of GERD has become a major concern due to its major health and economic impacts. Beyond the typical unpleasant symptoms, reflux can also be the source of severe, potentially life-threatening complications, such as aspiration.

Aim

Our aim was to support our hypothesis that the human body may in some cases develop various protective mechanisms to prevent these conditions.

Methods

Based on our experiences and review of the literature, we investigated the potential adaptive nature of seven reflux complications (hypertensive lower esophageal sphincter, achalasia, hypertensive upper esophageal sphincter, Zenker’s diverticulum, Schatzki’s ring, esophageal web, and Barrett’s esophagus).

Results

Patients with progressive GERD may develop diverse structural and functional esophageal changes that narrow the lumen of the esophagus and therefore reduce the risk of regurgitation and protect the upper aerodigestive tract from aspiration. The functional changes (hypertensive lower esophageal sphincter, achalasia, hypertensive upper esophageal sphincter) seem to be adaptive reactions aimed at easing the unpleasant symptoms and reducing acid regurgitation. The structural changes (Schatzki’s ring, esophageal web) result in very similar outcomes, but we consider these are rather secondary consequences and not real adaptive mechanisms. Barrett’s esophagus is a special form of adaptive protection. In these cases, patients report significant relief of their previous heartburn as Barrett’s esophagus develops because of the replacement of the normal squamous epithelium of the esophagus by acid-resistant metaplastic epithelium.

Conclusion

We believe that GERD may induce different self-protective reactions in the esophagus that result in reduced acid regurgitation or decreased reflux symptoms.
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2.

Purpose of review

Analysis of the esophageal microbiome remains a relatively new field of research, and most studies to date have focused on characterizing the esophageal microbiome in states of health and disease. Microbiome alterations have been implicated in the pathogenesis of inflammatory and neoplastic conditions in the colon and elsewhere in the gastrointestinal tract. The epidemiology of various esophageal conditions including Barrett’s esophagus (BE), esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), and eosinophilic esophagitis (EoE) point to the microbiome as a potential co-factor in disease pathogenesis, and the possibility exists that these microbiome alterations could contribute directly to the inflammatory environments necessary for the carcinogenesis or atopy involved in these conditions.

Recent findings

The native esophageal microbiome is similar in composition to the oral microbiome, with a high relative abundance of the phylum Firmicutes and the genus Streptococcus. Limited studies to date suggest that there are certain microbiome alterations associated with esophageal diseases. Additionally, it may be possible to indirectly assess the esophageal microbiome via non-endoscopic means. This raises the possibility that non-invasive microbiome analysis could be used for disease screening and monitoring.

Summary

Further understanding of the role of the esophageal microbiome in disease pathogenesis, as well as methods for microbiome alteration, may help elucidate future targets for disease modifying therapies, or minimally invasive screening tools in patients at high risk for development of various esophageal conditions.
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3.

Background

Use of an endocytoscopy system (ECS) makes it possible to omit biopsy histology for esophageal squamous cell carcinoma (ESCC). However, for differential diagnosis of ESCC, the endocytoscopic characteristics of esophagitis should be clarified.

Methods

We examined the morphology of surface cells in 20 cases of gastroesophageal reflux disease (GERD) (Grade M: 6 cases, A: 5 cases, B: 1 cases, C: 4 cases, D: 4 cases), five cases of candida esophagitis, and one case of eosinophilic esophagitis. One endoscopist classified the lesions using the modified type classification, and one pathologist judged the endocytoscopy images as “neoplastic”, “borderline”, or “non-neoplastic”.

Results

All cases of Grade M, A, and B GERD were classified as “type 1 or 2” by the endoscopist. However, 3/8 Grade C and D GERD lesions that had been diagnosed as regenerative squamous epithelium from biopsy histology were diagnosed as Type 3. All Grade M, A, and B cases were interpreted by the pathologist as “non-neoplastic”, whereas 4/8 Grade C and D GERD lesions, including three cases of regenerating epithelium, were diagnosed as “borderline” on the basis of ECS images. In 80 % of candida esophagitis cases, hyphae were visualized as white areas. Eosinophilic esophagitis showed a slight increase of cell density with marked infiltration of inflammatory cells.

Conclusion

Some cases of severe GERD cannot be clearly distinguished from esophageal squamous cell carcinoma (ESCC) using ECS, and therefore at present, cases of ESCC coexisting with severe GERD should not be diagnosed by ECS alone and probably require biopsy. (UMIN000007627).
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4.

Background

With heightened awareness of the increasing rate of esophageal adenocarcinoma and success of endotherapy for Barrett’s neoplasia, our Barrett’s center has seen a rise in referrals for evaluation and management of Barrett’s esophagus. We sought to compare the prevalence of neoplasia in patients with short- (<3 cm) versus long-segment Barrett’s esophagus (≥3 cm) referred to our Barrett’s center.

Methods

We performed a retrospective analysis of endoscopic procedures and pathology reports in adult patients (age >18) referred to our Barrett’s center over a 6-year period. Neoplasia was defined as low-grade dysplasia, high-grade dysplasia and superficial esophageal adenocarcinoma. Outcome measures included the prevalence of neoplasia in short- vs long-segment Barrett’s esophagus.

Results

Four-hundred and eighty-five patients (74 % male) were identified; 51 % had short-segment and 49 % had long-segment Barrett’s esophagus. The prevalence of neoplasia in short- vs long-segment Barrett’s esophagus was 33.6 vs 59.1 % (low-grade dysplasia 8.0 vs 14.5 %, high-grade dysplasia 12.8 vs 24.7 %, esophageal adenocarcinoma 12.8 vs 20.0 %). Long-segment Barrett’s esophagus was associated with 2.55-fold increase in odds of neoplasia relative to the short-segment group (OR 2.55, p < 0.001, CI 1.73–3.76).

Conclusion

Neoplasia was more prevalent in patients with long-segment Barrett’s. Surprisingly, 23.4 % of patients with an “irregular Z line” harbored advanced neoplasia (high grade dysplasia or esophageal adenocarcinoma) in our biased referral population. This suggests that patients with an “irregular Z line” should be biopsied and, if intestinal metaplasia is detected, surveyed per established Barrett’s esophagus guidelines.
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5.

Background

Eosinophilic esophagitis (EoE) is being recognized increasingly all over the globe; Indian data is however sparse. We screened patients with symptoms of gastroesophageal reflux disease (GERD) for presence of EoE in them.

Methods

Consecutive patients with symptoms suggestive of GERD underwent gastroduodenoscopy and esophageal biopsies, obtained from both the upper esophagus (5 cm below the upper esophageal sphincter) and lower esophagus (5 cm above gastroesophageal junction), as well as from any other endoscopically visible abnormal mucosa. Demographic and clinical characteristics, endoscopic findings, peripheral blood eosinophilic count, and history of use of proton-pump inhibitors (PPIs) were analyzed. Stool examination was done to rule out parasitoids. EoE was diagnosed if number of mucosal eosinophil infiltrate was >20 per high-power field. In the latter, Warthin-Starry stain was performed to rule out presence of H elicobacter pylori.

Results

Of 190 consecutive patients with symptoms of GERD screened, esophageal biopsies were available in 185 cases. Of them, 6 had EoE, suggesting a prevalence of 3.2% among patients with GERD. On univariate analysis, history of allergy, non-response to PPI, and absolute eosinophil counts and on multivariable analysis, history of allergy and no response to PPIs were significant predictors of EoE. Presence of EOE did not correlate with severity of reflux symptoms.

Conclusion

In this hospital-based study from northern part of India, prevalence of EoE in patients with GERD was 3.2%. EoE should be considered as a diagnostic possibility, especially in those with history of allergy, no-response to PPI, and absolute eosinophil count of ≥250/cumm.
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6.

Background and aims

Epidermal differential complex (EDC) proteins, such as filaggrin, involucrin, and loricrin, play key roles to protect the mucosal surface against invading pathogens. Eosinophilic esophagitis (EoE) is an allergic gastrointestinal disease that features eosinophilic infiltration of esophageal mucosa, though the function of EDC proteins in its pathogenesis remains unknown. The aim of this study was to investigate possible differences of EDC protein expression in the epithelium of the esophagus, pharynx, and tongue. Furthermore, we examined that expression in esophageal specimens obtained from patients with EoE.

Methods

For evaluating EDC protein expression in epithelium from different locations, we enrolled 72 patients who underwent surgical resection for esophageal, pharyngeal, or tongue squamous cell carcinoma. Pathological samples were used for analysis of expression by immunohistochemistry. In addition, samples were obtained from 10 patients with EoE and 11 healthy subjects, and compared for esophageal epithelial expression of EDC proteins.

Results

In epithelium samples obtained from the esophagus, pharynx, and tongue, the presence of EDC proteins was confirmed by immunohistochemistry analysis findings, though the expression patterns were notably different in comparison to that in epidermis samples. In EoE patients, the expression of involucrin was dramatically down-regulated in esophageal mucosa, whereas down-regulation of filaggrin and loricrin did not reach a statistically significant level.

Conclusion

EDC protein expression was clearly detected in pharyngoesophageal epithelium samples, while that of involucrin alone was markedly reduced in patients with EoE.
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7.

Purpose of Review

In this review, we discuss current diagnostic testing modalities for both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) and then introduce mucosal impedance (MI), a novel technology that measures epithelial integrity in real time during endoscopy. We describe the advantages and disadvantages of MI as compared with traditional diagnostic testing.

Recent Findings

We review studies that demonstrate that GERD and EoE have distinct MI patterns, and that physicians can accurately diagnose and distinguish the two during endoscopy with minimal time added to the procedure. We also review studies showing that MI has the capability to assess treatment response in both GERD and EoE and that it can be used to diagnose GERD in patients with extraesophageal reflux symptoms.

Summary

Mucosal impedance testing is a major advancement in the diagnosis of GERD and EoE. Future studies are planned to assess whether MI can be used as a treatment endpoint in EoE and whether it can be used to predict response to anti-reflux surgery.
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8.

Backgrounds

The objectives of this study were to delineate differences in the morphologic characteristics of reflux esophagitis between a rat gastroesophageal reflux (GER) model and a duodenoesophageal reflux (DER) model and to evaluate the effects of H2-receptor antagonists on morphologic characteristics of reflux esophagitis in DER model.

Methods

Wistar rats were divided into 3 groups: GER model group (Group G), DER model group (Group D), and control group (Group C). Rats in each group were sacrificed 1 or 12 weeks after surgery. Intraesophageal pH was measured, and the excised esophagus was examined macroscopically and histologically. Subgroups of rats in Group D were given famotidine (10 mg/kg) or lafutidine (30 mg/kg) orally once daily for 1 week after surgery. The rats were then sacrificed, and histological findings were compared.

Results

Intraesophageal pH was significantly lower in Group G than in Group C. At 12 weeks, the epithelium of the lower esophagus in Groups G and D was significantly thicker than that in Group C and showed remarkable hyperplastic changes in Group D. The thickness of the epithelium in Group D + famotidine did not differ significantly from that in Group D. In contrast, the epithelium was significantly thinner in Group D + lafutidine than in Group D.

Conclusions

As a rat model of reflux esophagitis, DER causes severer damage to the esophageal epithelium, including hyperplastic changes, than does GER. Famotidine had no apparent effect on esophageal epithelial damage caused by DER, whereas lafutidine was suggested to attenuate such damage.
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9.

Aim and methods

The Japan Esophageal Society created a working committee group consisting of 11 expert endoscopists and 2 pathologists with expertise in Barrett’s esophagus (BE) and esophageal adenocarcinoma. The group developed a consensus-based classification for the diagnosis of superficial BE-related neoplasms using magnifying endoscopy.

Results

The classification has three characteristics: simplified, an easily understood classification by incorporating the diagnostic criteria for the early gastric cancer, including the white zone and demarcation line, and the presence of a modified flat pattern corresponding to non-dysplastic histology by adding novel diagnostic criteria. Magnifying endoscopic findings are composed of mucosal and vascular patterns, and are initially classified as “visible” or “invisible.” Morphologic features were evaluated for “visible” patterns, and were subsequently rated as “regular” or “irregular,” and the histology, non-dysplastic or dysplastic, was predicted.

Conclusion

We introduce the process and outline of the magnifying endoscopic classification.
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10.

Purpose of Review

Esophageal adenocarcinoma bears one of the fastest rising incidence of any cancers and generally arises in the setting of gastroesophageal reflux and Barrett’s esophagus. However, early detection of neoplasia can be challenging since most patients are asymptomatic until they progress to more advanced and less curable stages, and early dysplastic lesions can be small, multifocal, and difficult to detect. Clearly, new imaging tools are needed in light of sampling error associated with random biopsies, the current standard of practice.

Recent Findings

Advances in endoscopic imaging including virtual chromoendoscopy, confocal laser endomicroscopy, and subsurface imaging with optical coherence tomography have ushered in a new era for detecting subtle neoplastic lesions. Moreover, in light of esophagus-sparing treatments for neoplastic lesions, such tools are likely to guide ablation and follow-up management.

Summary

While there is no ideal single imaging modality to facilitate improved detection, staging, ablation, and follow-up of patients with dysplastic Barrett’s esophagus, new advances in available technology, the potential for multimodal imaging, and the use of computer-aided diagnosis and biomarkers all hold great promise for improving detection and treatment.
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11.

Background

Barrett’s esophagus (BE) is a known complication of gastroesophageal reflux disease. In a previous study, we described a high prevalence of intestinal metaplasia (IM) in patients with an irregular Z line. However, the clinical importance of this finding is unclear.

Goals

To evaluate the long-term development of BE and relevant complications in patients diagnosed with an irregular Z line, with or without IM, on routine esophago-gastro-duodenoscopy (EGD).

Methods

In our previously described cohort, 166 out of 2000 consecutive patients were diagnosed with an incidental irregular Z line. Of those with irregular Z line, 43% had IM. In this continuation study, patients’ status was reassessed after a median follow-up of 70 months. Patients were divided into two groups: Patients with IM (IM-positive group) and without IM (IM-negative group). The incidence of long-term development of BE, dysplasia, and esophageal adenocarcinoma were compared between groups.

Results

At least one follow-up EGD was performed in 102 (61%) patients with an irregular Z line. Endoscopic evidence of BE was found in eight IM-positive patients (8/50 [16%]) and in one IM-negative patient (1/52 [1.9%]). Two (4%) IM-positive patients developed BE with low-grade dysplasia. None of the patients developed high-grade dysplasia, or esophageal adenocarcinoma.

Conclusions

Patients with irregular Z line do not develop major BE complication in more than 5 years of follow-up.
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12.

Background

Gastroesophageal reflux disease (GERD) is the most common chronic gastrointestinal disorder, affecting one third of the population worldwide. Recently, there has been a renewed interest in Stretta therapy in view of potential long-term side effects of PPIs and the durability of relief with fundoplication.

Method

Prospective randomized study comparing the Stretta treatment with controls receiving PPIs. Patient (>?18 years, n = 20) with symptoms of heartburn, regurgitation, abnormal esophageal acid exposure (≥?4%), and endoscopically confirmed esophagitis were included into the study. The primary measure was improvement in quality of life (QOL) and decrease in the frequency and severity of GERD symptoms.

Results

The mean age of the patients was 39 (±?15) years and controls were 34 (±?11) years. Three months after Stretta, 80% reported improvement in QOL compared to 40% in the control group. At the end of 3 months, significant (p < 0.05) improvement in GERD symptom score for heartburn, regurgitation, chest pain, and cough compared with the control group was observed. After Stretta treatment, 60% of the patients were free of PPIs whereas there was no change in the control group. Almost 80% of the patients on Stretta treatment were satisfied with the treatment compared to 30% of the patients in the control group.

Conclusion

Stretta was effective in the short-term for the management of GERD.
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13.

Purpose of Review

The cellular origins of Barrett’s esophagus remain elusive. In this review, we discuss the potential cellular mechanisms behind squamous to columnar metaplasia as well as the limitations of these proposed mechanisms.

Recent Findings

Several theories have been proposed, including the reprogramming of native squamous cells, repopulation from submucosal glands, contributions from circulating bone marrow-derived cells, and direct extension of gastric cells. Most recent data support an innate progenitor cell unique to the squamocolumnar junction that can expand into metaplastic glands.

Summary

Active investigation to clarify each of these potential cells of origin is being pursued, but ultimately each could contribute to the pathogenesis of Barrett’s esophagus depending on the clinical context. Nonetheless, identifying cells of origin is critical to understand the molecular mechanisms behind Barrett’s esophagus and developing strategies to better treat (and possibly prevent) this increasingly significant premalignant disease.
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14.

Background

Esophageal rupture, spontaneous or iatrogenic, is associated with significant morbidity and mortality. The current study aims at highlighting the various clinical scenarios, where esophageal fully covered self-expanding removable metal stents (FCSEMS) can be used in esophageal rupture.

Methods

In patients who underwent insertion of FCSEMS between January 2013 and June 2014, all data regarding demographics, indications, insertion, removal, and outcomes were studied retrospectively.

Results

Seven patients underwent the placement of esophageal covered SEMS. Two patients had Boerhaave syndrome, two had leak following the repair of aortic aneurysm, one had extensive esophageal injury following transesophageal echocardiography, one had carcinoma esophagus with tracheaesophageal fistula, and one had dehiscence of esophagogastric anastomosis. Stent insertion was successful in all the patients; one had stent migration which was managed endoscopically. Two patients died due to underlying illness; the rest had successful removal of stents after 8–10 weeks and good outcomes.

Conclusion

Esophageal FCSEMS placement is safe and effective modality in management of patients with esophageal rupture.
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15.

Background

Eosinophilic gastritis (EG) and eosinophilic gastroenteritis (EGE) are chronic immune-mediated conditions of the digestive tract, which affect the stomach only, or the stomach and small intestines, respectively. Though these disorders are uncommon, they are being increasingly recognized and diagnosed. While health-related quality of life (HRQOL) has been evaluated in other eosinophilic gastrointestinal diseases, this study is the first to describe HRQOL impacts unique to EG/EGE.

Aims

This study aims to qualitatively describe experiences of adults diagnosed with EG and EGE. We aim to identify impacts on HRQOL in this population in order to inform clinical care and assessment.

Methods

Seven patients diagnosed with EG or EGE participated in semi-structured interviews assessing common domains of HRQOL.

Results

Four distinct themes emerged from qualitative analyses, which represent impacts to HRQOL: the psychological impact of the diagnosis, impact on social relationships, financial impact, and impact on the body. These generally improved over time and with effective treatment.

Conclusions

This study demonstrated that patients with EG/EGE experience impacts to HRQOL, some of which differ from HRQOL of other eosinophilic gastrointestinal diseases. These results support the development of a disease-specific measure, or adaptation of an existing measure, to assess HRQOL in EG/EGE.
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16.

Back ground

Benign esophageal stricture is a common cause for dysphagia in adults. It can negatively affect the quality of patient’s life and may cause many complications. Benign esophageal strictures are caused by different procedures and disorders, such as gastroesophageal reflux disease, post-surgery anastomotic stricture, radiation, ablative therapy or caustic ingestion. The aim of the study was to assess the efficacy of Polyflex stent insertion in refractory benign esophageal strictures in patients admitted to the endoscopy unit of the Medical Research Institute hospital, Alexandria University, Alexandria, Egypt.

Patients and methods

Polyflex, self-expandable plastic stent, were inserted in nine patients with refractory benign esophageal strictures with follow-up for 1 year.

Results

Dysphagia was significantly improved in 88% of patients, after insertion of Polyflex stents. Complications reported were one patient with stent migration and 2 patients with esophageal ulceration.

Conclusion

The use of Polyflex stents in the management of benign refractory esophageal strictures appears to be promising with high clinical success rate and few manageable complications.
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17.

Purpose of Review

This review addresses the similarities and differences between the spastic esophageal disorders, including jackhammer esophagus, distal esophageal spasm (DES), and type III (spastic) achalasia. The pathophysiology, diagnosis, and treatment of each separate disorder are discussed herein, with an emphasis on overlapping and discordant features.

Recent Findings

The Chicago Classification is a hierarchical organizational scheme for esophageal motility disorders, currently in its third iteration, with direct impact on the definitions of these three disorders. Complementary diagnostic tools such as impedance planimetry and novel manometric parameters continue to evolve. The suite of potential treatments for these disorders is also expanding, with progressive interest in the role of peroral endoscopic myotomy alongside established pharmacologic and mechanical interventions.

Summary

Although jackhammer esophagus, distal esophageal spasm, and type III achalasia frequently overlap in terms of their clinical presentation and available management approaches, the divergences in their respective diagnostic criteria suggest that additional study may reveal additional mechanistic distinctions that lead in turn to further refinements in therapeutic decision-making.
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18.

Introduction

Endoscopic extraction is the first choice for removing esophageal foreign bodies, but dentures with complicated sharp clasps that invaginate the esophageal mucosa are difficult to remove endoscopically; surgical management is required for patients who have ingested dentures.

Methods

Seven patients who underwent emergency surgery for dentures with complicated sharp clasps lodged in the cervicothoracic esophagus were enrolled. We describe the surgical management and postoperative courses of these patients.

Results

There were four male and three female patients with an average age of 78.4 years (range 71–84). All cases were difficult to diagnosis by interview because the patients had dementia or schizophrenia. Emergency surgery was performed for seven patients. A skin incision was made along the anterior border of the left sternocleidomastoid muscle. The esophageal wall was opened and the denture was extracted. The esophageal wall was repaired with interrupted sutures. A tracheostomy was constructed in three cases, and bilateral drainage was performed in two cases. However, tracheostomy and bilateral drainage were not necessary, and the subsequent four patients received only left-sided drainage tubes without tracheostomy. All seven patients progressed favorably postoperatively. No ruptured sutures or esophageal stenosis occurred.

Conclusion

The outcomes of all seven patients who underwent surgical denture removal were satisfactory. Tracheostomy and bilateral drainage may not be essential.
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19.

Purpose of Review

Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.

Recent findings

Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation.

Summary

While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.
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20.

Background and objective

Pulmonary metastasectomy is a standard therapy for some types of metastatic lesions in the lung. Although the prognosis for esophageal cancer patients with pulmonary metastasis is poor, it has been reported that some post-esophagectomy patients have good prognosis after pulmonary metastasectomy. We investigated the role of resecting pulmonary metastases arising from esophageal cancer at our institution.

Patients and methods

Seven patients with primary squamous cell carcinoma or adenocarcinoma of the thoracic esophagus who underwent resection of metachronous pulmonary metastases at our institution between 2006 and 2012 were identified from a retrospective database. All patients had undergone curative resection of their primary esophageal carcinoma.

Results

Six patients had unilateral and solitary lung metastasis. One patient presented with one metastatic lesion on each side, and he underwent 4 metastasectomy for pulmonary metastasis 3 times. There was no perioperative morbidity or mortality. The disease-free interval after esophagectomy ranged from 191 to 559 days (median, 463 days). Survival after pulmonary metastasectomy ranged from 357 to 3191 days (median, 1803 days). Three patients received systemic chemotherapy before metastasectomy. Currently, 5 patients are alive without evidence of recurrent disease.

Conclusion

Pulmonary metastasectomy may be acceptable as a part of multimodal treatment for solitary metachronous pulmonary metastasis in esophageal carcinoma.
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