Eosinophilic esophagitis: time for clinical practice

Use of esophageal stent for the treatment of postoperative gastrointestinal–airway fistula after esophagectomy Abstract A gastrointestinal–airway fistula (GAF) after esophagectomy is a very serious postoperative complication that can cause severe respiratory complications due to digestive juice inflow. Generally, GAF is managed by invasive surgical treatment; less-invasive treatment has yet to be established. We performed esophageal stent placement (ESP) in three cases of GAF after esophagectomy. We assessed the usefulness of ESP through our clinical experience. All GAFs were successfully managed by ESP procedures. After the procedure, the stent positioning and expansion were appropriately evaluated by radiological assessments over time. The stent was removed after endoscopic confirmation of fistula closure on days 8, 23, and 71. Only one patient with a long-term indwelling stent developed a manageable secondary gastrobronchial fistula as a procedure-related complication. In conclusion, ESP was shown to be a less-invasive and effective therapeutic modality for the treatment of GAF.

Efficacy of long-term maintenance therapy with 10-mg vonoprazan for proton pump inhibitor-resistant reflux esophagitis Abstract Background To investigate the efficacy of long-term (52 weeks) maintenance therapy by 10-mg vonoprazan administration for proton pump inhibitor-resistant reflux esophagitis continued from the preceding study. Methods Sixteen patients with proton pump inhibitor-resistant reflux esophagitis (mean age 70.9 years, eight males) in whom endoscopic healing was achieved by 20-mg vonoprazan administration for 4 weeks and maintenance of remission was maintained by 10-mg vonoprazan administration for 8 weeks were enrolled. Endoscopy was performed at 52 weeks after the initiation of maintenance therapy with 10-mg vonoprazan to evaluate whether there was any recurrence of reflux esophagitis. Changes in the gastric mucosa were investigated at 52 weeks. Symptoms were assessed using the frequency scale for the symptoms of gastroesophageal reflux disease and the fast gastrin level at 8 and 52 weeks following the maintenance therapy. Results Endoscopic remission was maintained at 52 weeks in 15 (93.8%) of the 16 patients with proton pump inhibitor-resistant reflux esophagitis. One patient relapsed with grade C of reflux esophagitis. There were no significant differences in the symptom score at 8 and 52 weeks, nor the gastrin level at 8 and 52 weeks. There was no change in the stomach on endoscopy at 52 weeks. Conclusion Long-term maintenance therapy by 10-mg vonoprazan administration is very effective for proton pump inhibitor-resistant reflux esophagitis patients in whom endoscopic healing was maintained by 8 weeks maintenance therapy with 10-mg vonoprazan administration.

Ivor–Lewis esophagectomy for patients with squamous cell carcinoma of the thoracic esophagus with a history of total pharyngolaryngectomy Abstract Background Synchronous or metachronous esophageal, and head and neck cancers are often observed, and we occasionally encounter esophageal cancer cases with a past history of total pharyngolaryngectomy (TPL) for head and neck cancers. Total esophagectomy after TPL may impair blood supply to the trachea and may cause tracheal necrosis. Meanwhile, Ivor–Lewis esophagectomy can prevent the above-mentioned risks, but there is a concern about an anastomosis with the remnant upper esophagus that lost blood supply after two surgical procedures. The surgical outcomes of Ivor–Lewis esophagectomy after TPL remain unclear. Therefore, we investigated the surgical outcomes. Methods This study included patients who underwent Ivor–Lewis esophagectomy for esophageal cancer with a history of TPL at our institution between 2005 and 2017. We retrospectively investigated the patients’ background characteristics and short-term surgical outcomes. Results Twelve consecutive patients (8 men and 4 women) were included in this study. The median period between TPL and esophagectomy was 32 months (range 2–185 months). All patients underwent esophagectomy via right open thoracotomy and reconstruction using a gastric tube with intrathoracic anastomosis. Although the esophagogastric anastomosis was made on the remnant upper esophagus, which had already lost blood supply from the inferior thyroid artery, there was no case of anastomotic leakage or esophageal necrosis, and hospital mortality was not observed. Conclusion Ivor–Lewis esophagectomy for patients with a history of TPL is a safe procedure, which can prevent severe complications including anastomotic leakage or tracheal necrosis.

Evaluation of the impact of psoas muscle index, a parameter of sarcopenia, in patients with esophageal squamous cell carcinoma receiving neoadjuvant therapy Abstract Background The impact of sarcopenia on digestive cancer is widely known. Muscle mass, defined as the psoas muscle index (PMI), is an important parameter of sarcopenia. However, the relationship between esophageal cancer and PMI has not been fully investigated, especially in patients receiving neoadjuvant therapy. Methods To elucidate the influence of the PMI on patients with esophageal squamous cell carcinoma receiving neoadjuvant therapy, the progression of sarcopenia defined by the PMI, the relationship between pretherapeutic/preoperative sarcopenia and patient characteristics, and patient survival were retrospectively investigated in 82 patients with esophageal squamous cell carcinoma who underwent neoadjuvant therapy. Results The PMI decreased by more than 20 mm2/m2 between the pretherapeutic and preoperative periods in 75.6% of the patients. Pretherapeutic sarcopenia (low PMI) correlated with the pathological therapeutic response, postoperative recurrence, and pretherapeutic body mass index. Neoadjuvant chemoradiotherapy was associated with the progression of sarcopenia. The pretherapeutic sarcopenia group (low PMI) had worse disease-free survival (DFS) than the non-sarcopenia group. Furthermore, pretherapeutic sarcopenia (low PMI) was an independent prognostic risk factor of DFS according to univariate and multivariate analyses. Conclusions The PMI may decrease during neoadjuvant therapy, especially during neoadjuvant chemoradiotherapy. Pretherapeutic sarcopenic (low PMI) patients should be followed-up more carefully postoperatively because higher risks of recurrence and poorer rates of disease-free survival are associated with these patients.

Comparing the 7th and 8th editions of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for esophageal squamous cell carcinoma treated by definitive radiotherapy Abstract Background We retrospectively compared the 7th and the 8th editions of The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM classification in the cohort of survival of the patients with esophageal squamous cell carcinoma (ESCC) treated by definitive radiotherapy. Methods We included in this study 403 patients with ESCC who underwent radiotherapy or chemoradiotherapy, at a total radiation dose of ≥ 50 Gy with curative intent from 2000 to 2016 at Kindai University Hospital, and who had no distant metastasis (excluding supraclavicular lymph node). The same patient data set was re-staged according to both the 7th and 8th editions of AJCC/UICC TNM classification. Results For the 7th edition, 5-year overall survival (OS) for stages I, II, III, and IV were 58%, 52%, 22%, and 12%, respectively, which seemed to be separable into two groups (Stages I–II and III–IV). In the 8th edition, corresponding values for stages I, II, III, and IV were 65%, 44%, 34%, and 16%, respectively, which seemed to be separated into three groups (Stage I, II–III, and IV). Conclusions The 8th edition of AJCC/UICC TNM classification is a useful predictor of OS among ESCC patients who were treated with definitive radiotherapy.

Gastric mucosal injury and hemorrhage after definitive chemoradiotherapy for locally advanced esophageal cancer Abstract Background Definitive chemoradiotherapy is one of the treatment options for locally advanced esophageal cancer with curative intent. Esophagitis and pharyngitis are well-known adverse events that occur during chemoradiotherapy, but gastric mucosal injury has been less frequently reported compared to mucositis. Importantly, gastric mucosal injury is not well known, hard to manage, and sometimes fatal. Hence, we examined the clinical characteristics and the incidence of gastric mucosal injury after CRT for esophageal cancer. Methods The medical records of patients who received definitive chemoradiotherapy combined with 5-fluorouracil and cisplatin for stage II/III (nonT4) esophageal squamous cell carcinoma from January 2001 to December 2010 at our institute were reviewed retrospectively. Results We investigated 256 patients in whom, data for endoscopic abdomen examinations were both before and after CRT were available. Gastric mucosal damage was observed in 90 patients (35%) (grade 1/2/3 = 69/18/3). One of the possible risk factors identified in this study was the irradiation dose to abdomen. Compared to patients with cervical esophagus–upper thoracic esophagus tumor location, patients with middle thoracic esophagus–abdominal esophagus tumor location were more likely to develop gastric mucosal damage, although there was no statistically significant difference. Conclusions It is important to consider gastric mucosal injury in patients who receive CRT, particularly when the irradiation field includes stomach.

A low surgical Apgar score is a predictor of anastomotic leakage after transthoracic esophagectomy, but not a prognostic factor Abstract Background The surgical Apgar score (SAS) has been a useful predictor of postoperative complications in several types of cancer. However, there are few reports about the correlation of SAS and esophageal cancer. This study aimed to examine the utility of SAS as a predictor of major complications, particularly anastomotic leakage, in patients who underwent transthoracic esophagectomy, and investigate the correlation between SAS and patient prognosis. Methods This is a single-center, retrospective observational study. A total of 190 patients who underwent esophagectomy for esophageal cancer in 2012–2016 were reviewed to find the correlation between SAS and postoperative complications (Clavien–Dindo classification III or higher). SAS was calculated based on intraoperative estimated blood loss, lowest mean arterial pressure, and lowest heart rate. Major complications included anastomotic leakage, respiratory, cardiac, recurrent nerve palsy, chylothorax, and other complications. We also reviewed how SAS was correlated with 3 year overall survival (OS) and recurrence-free survival (RFS). A high SAS was defined as ≥ 6, and a low SAS as < 6. Results On univariate analysis, SAS showed a statistical significance in all major complications and anastomotic leakage. On multiple logistic regression analysis, a low SAS was detected as a risk factor of the major complications and anastomotic leakage, with a significant difference. Moreover, we conducted survival analysis with SAS; however, we could not detect that a low SAS had a negative impact on OS and RFS. Conclusions A low SAS can be a predictor of postoperative complications, especially anastomotic leakage. However, SAS was not correlated with OS or RFS.

Impact of tumor-infiltrating LAMP-3 dendritic cells on the prognosis of esophageal squamous cell carcinoma Abstract Background Dendritic cells (DCs) are the most potent antigen-presenting cells to induce cytotoxic T lymphocytes in the tumor environment. After acquiring antigens, DCs undergo maturation and their expression of MHC and co-stimulation molecules are enhanced, along with lysosome-associated membrane glycoprotein 3 (LAMP-3), which is a specific marker of mature DCs. In general, mature DCs are usually considered to be immunostimulatory in the cancer microenvironment. In addition, it is known that tumor-infiltrating lymphocytes (TILs) are associated with a good prognosis in esophageal squamous cell carcinoma (ESCC). However, few studies have targeted the interaction between DCs and TILs in the local immunity of ESCC. We investigated the localization of mature DCs within ESCC tissue and their relationship to TILs as well as the clinical outcome. Methods We evaluated 80 ESCC patients who underwent surgical treatment without preoperative treatment, using immunohistochemistry with LAMP-3 and CD8. Results The results showed that LAMP-3 DCs were predominantly observed in the peritumoral area. Intratumoral CD8 T cells were found to be associated with a favorable prognosis, and the number of infiltrating LAMP-3 DCs was correlated with the number of intratumoral CD8 T cells. Conclusion At the local tumor site, mature LAMP-3 DCs might be associated with increasing tumor infiltrating CD8 T cells.

Evaluation of the efficacy of Hypericum perforatum (St. John’s wort) oil in the prevention of stricture due to esophageal corrosive burns Abstract Background/purpose The inflammatory response that follows the caustic burns results in fibrosis on the esophageal wall leading to esophageal stricture, dysphagia, and malnutrition. The controversy over the use of corticosteroids warrants alternative therapeutic interventions. We investigated the effect of extracts from St. John’s wort (SJW) with known wound-healing activity on stricture formation in rat esophageal injury models. Methods Five experimental groups were involved: sham group with no injury, control group with injury without treatment, and three different treatment groups (methylprednisolone, SJW extract, and combination of the two). Histopathological examination of esophageal damage and collagen accumulation, stenosis index, and tissue hydroxyproline levels were used to assess stricture and the effect of treatments. Results There was a significant weight loss in all groups except for those without injury and those treated with SJW extract, the latter gained weight albeit not significant. Stenosis index was increased in all groups compared to sham but not significantly in those treated with SJW extract. Histopathological and biochemical analyses produced mixed results. Conclusions Some of the experimental indicators such as weight gain and stenosis index suggested the treatment of esophageal injury models using extracts of St. John’s wort effective while other histopathological indicators show no significant benefit.