Reflux esophagitis after esophagectomy: impact of duodenogastroesophageal reflux.

Reflux esophagitis (RE) is a known complication disturbing patients' quality of life after esophageal resection. It is generally recognized that bile reflux as well as acid reflux cause RE. However, the clinical influence of acid and bile reflux, and Helicobacter pylori (H. pylori) infection on RE in the cervical esophagus after esophagectomy is not yet clarified. Sixty patients who underwent cervical esophagogastrostomy following esophagectomy were enrolled in this study. They underwent examination for H. pylori infection, endoscopic examination, and continuous 24-hour pH and bilirubin monitoring, at 1 month after surgery. The influence of acid and/or bile reflux, H. pylori infection, and others on the development of RE were investigated. RE was observed in 19 patients (32%) at 1 month after esophagogastrostomy, mild RE in 16 (27%), and severe RE in 3 (5%). The percentage of time duration of both acid and bile reflux into the cervical esophagus was higher in patients with RE than in those without (P = 0.027, P < 0.001). A significant difference in %time pH < 4 acid reflux was found between mild RE and severe RE (P = 0.014), and a statistical difference in %time abs. > 0.14 between non-RE and mild RE (P = 0.017). Acid and/or bile reflux was observed in 31 patients (52%), acid-only reflux in 6 (10%), bile-only reflux in 15 (25%), and acid-and-bile reflux in 10 (17%). Severe RE was observed only in patients having acid-and-bile reflux. On the univariate analysis, no infection of H. pylori, acid reflux, and bile reflux were determined to be the influencing factors to RE among the clinical factors including age, gender, route of esophageal reconstruction, H. pylori infection, and acid-and-bile reflux. In the subanalysis using the logistic model, there were significant correlations between bile reflux and RE irrespective of the presence of H. pylori infection (P = 0.016, P = 0.007). On the other hand, there was a significant correlation between acid reflux and RE only in patients without H. pylori infection (P = 0.039). In the early period after esophagogastrostomy, bile reflux could cause RE irrespective of H. pylori infection, while acid reflex could cause RE only in patients without H. pylori infection. There is a possibility that bile reflux plays an important role in the development of RE after esophagectomy.

Thoracic endovascular aortic repair for aortic complications after esophagectomy for cancer: report of three cases.

Aortic complications after esophageal cancer surgery are rare and usually fatal. Here, we report three patients who underwent thoracic endovascular aortic repair (TEVAR) for aortic complications after esophagectomy for cancer. In the first case, aortic rupture was caused by pyothorax due to residual tumor after esophagectomy. In the second case, aortic rupture was caused by pyothorax due to anastomotic leakage. In the third case, a pseudoaneurysm was caused by surgical injury during esophagectomy. TEVAR was safe and effective for severe aortic complications when graft infection was avoided. The first case died of sepsis on the 84th postoperative day, and the other two cases have survived 4 years and 2 years to date.

What influences the acidity in the gastric conduit in patients who underwent cervical esophagogastrostomy for cancer?

The aim of this study was to determine the factors influencing acidity in the gastric conduit after esophagectomy for cancer. Acidity and bile reflux in the stomach and in the gastric conduit were examined by 24-h pH monitoring and bilimetry in 40 patients who underwent transthoracic subtotal esophagectomy followed by esophageal reconstruction using a gastric conduit, which was pulled up to the neck through a posterior mediastinal route in 17 patients, through a retrosternal route in 10 patients, and through a subcutaneous route in 13 patients. They were examined at 1 week before surgery, at 1 month after surgery, and at 1 year after surgery. Helicobacter pylori infection was examined pathologically and using the (13) C-urea breath test. The factors influencing acidity of the gastric conduit were analyzed using the stepwise regression model. Gastric acidity assessed by percentage (%) time of pH < 4 was reduced after surgery and was significantly less in patients with H. pylori infection compared with those without H. pylori infection throughout the period from 1 week before surgery to 1 year after surgery. Duodenogastric reflux (DGR) assessed by % time absorbance > 0.14 into the lower portion of the gastric conduit was significantly increased after surgery throughout the period from 1 month after surgery to 1 year after surgery. Multivariate analysis showed that the acidity in the gastric conduit was influenced by H. pylori infection and DGR at 1 month after surgery, and by H. pylori infection and the route for esophageal reconstruction at 1 year after surgery. Acidity in the gastric conduit was significantly decreased after surgery. Acidity in the gastric conduit for esophageal substitutes is influenced by H. pylori infection and surgery. DGR influences the gastric acidity in the short-term after surgery, but not in the long-term after surgery.

Outcomes of multimodality therapy for stage IVB esophageal cancer with distant organ metastasis (M1-Org).

Esophageal cancer patients with distant organ metastasis have usually been treated only to palliate symptoms without multimodality therapy. The current study evaluates the role of multimodality therapy in esophageal squamous cell cancer patients with distant organ metastasis. Between February 1988 and January 2007, 80 esophageal squamous cell cancer patients with distant organ metastases were treated at our institution. Multimodality therapy was performed in 58 patients: 43 patients received chemoradiotherapy, 13 underwent surgery followed by chemotherapy and/or radiation therapy, and two received chemotherapy or chemoradiotherapy followed by surgery. Thirteen patients received single-modality therapy; chemotherapy, radiotherapy, or surgery alone. The remaining nine patients received best supportive care alone. The metastatic organ was the liver (n= 40), the lungs (n= 33), bone (n= 10), and other (n= 6). Nine patients had metastasis in two organs. There was no difference in the median survival among the sites of organ metastasis, lung, liver, or bone (P= 0.8786). The survival of patients treated with multimodality therapy was significantly better than that of the patients who received single-modality therapy or best supportive care alone (P < 0.0001). In patients treated with multimodallity therapy, there was no difference in survival for patients treated with surgery compared with patients treated without surgery (P= 0.1291). This retrospective study involves an inevitable issue of patient selection bias. However, these results suggested that multimodality therapy could improve survival of the esophageal squamous cell cancer patients with distant organ metastasis.

Surgical management for small cell carcinoma of the esophagus.

Esophageal small cell carcinoma (SmCC) has been regarded as a rare and aggressive tumor with early metastasis. The optimal treatment has not yet been established, and the role of surgery has remained controversial. In this retrospective study, we report seven cases studies of SmCC of the esophagus and analyze the clinical outcomes after surgery. Between 1986 and 2007, there were seven patients with esophageal SmCC treated surgically in our institution. All the patients with clinically limited disease underwent transthoracic esophagectomy with lymphadenectomy. Lymph node involvement was found in all cases irrespective of the depth of tumor invasion. Three of the seven patients were diagnosed as having an extensive disease on pathological examination after esophagectomy. Five patients received postoperative chemotherapy. Two patients are alive with no recurrence at 16 months and at 45 months after surgery. Another one without chemotherapy survived 93 months and died of another disease. The remaining four patients died of recurrent disease or another disease. The median overall survival to date of these patients was 16 months (range 12-93 months). Esophagectomy with lymphadenectomy resulted in a relatively better survival in some patients with esophageal SmCC. We concluded that surgery may be helpful as part of multimodality treatment in selected patients with esophageal SmCC.

Pharyngolaryngeal reflux in patients who underwent cervical esophago-gastrostomy following esophagectomy.

Pharyngolaryngeal reflux has been generally accepted as a cause for pharyngolaryngitis, hoarseness, aspiration pneumonia, chronic cough, and nocturnal asthma. Although patients who have undergone gastric conduit reconstruction after esophagectomy are at a high risk to pharyngolaryngeal reflux disease (PLRD), PLRD after esophagectomy is still unknown. The aim of this study is to investigate the correlation between reflux pharyngolaryngitis and acid reflux into the hypopharynx and into the cervical esophagus in patients who have undergone cervical esophagogastrostomy. We enrolled 62 patients who received follow-up endoscopy and 24-h pH monitoring after cervical esophagogastrostomy. These included 26 at 1 month after surgery and 36 at 1 year or more after surgery. We investigated: (i) the correlation between the extent of reflux pharyngolaryngitis and that of reflux esophagitis based on endoscopic findings; and (ii) the correlation between the extent of reflux pharyngolaryngitis and that of acid exposure -'% time pH < 4' measured by 24-h pH monitoring - in the hypopharynx and in the cervical esophagus, and of acidity in the gastric conduit. There was no difference in acid exposure between the hypopharynx and the cervical esophagus according to time after surgery. However, the acidity in the gastric conduit was significantly more at one year or more after surgery compared with acidity at 1 month after surgery (P= 0.001). There was a significant correlation between acid exposure in the hypopharynx and that in the cervical esophagus (P < 0.001), although acid exposure in the hypopharynx was significantly less than that in the cervical esophagus (P < 0.001). A significant correlation between reflux pharyngolaryngitis and reflux esophagitis was observed (P < 0.001). There was a significant correlation between reflux pharyngolaryngitis and acid exposure in the hypopharynx (P= 0.021), and also that in the proximal esophagus (P= 0.001). The correlation between the extent of reflux pharyngolaryngitis and the acidity in the gastric conduit was not observed. These findings are consistent with pharyngolaryngitis being caused by gastro-esophago-pharyngolaryngeal reflux in patients after cervical esophagogastrostomy, despite the upper esophageal sphincter strongly preventing acid reflux from the cervical esophagus into the hypopharynx.

Endoscopic classification for reflux pharyngolaryngitis.

The quality of life in patients who have undergone surgery for esophageal cancer is frequently disturbed by postoperative gastroesophageal reflux disease or pharyngolaryngeal reflux disease. Recently, there have been many reports on gastroesophageal reflux disease after esophagectomy, and only a few on pharyngolaryngeal reflux disease. There is not yet any convenient endoscopic classification of reflux pharyngolaryngitis. We designed a new classification for reflux pharyngolaryngitis based on endoscopic findings. Our new classification consists of the five grades from 0 to IV based on (i) the extent and severity of erythema and/or edema in the pharynx and the larynx, and (ii) the extent and severity of granulation or scarring stenosis in the vocal cords. Ninety-three patients after cervical esophagogastrostomy after esophagectomy (the CEG group) and 28 patients after intrathoracic esophagogastrostomy (the TEG group) were reviewed in this study. We investigated the relation between the severity of reflux pharyngolaryngitis and clinical symptoms in these patients, and the correlation between this new classification of reflux pharyngolaryngitis and the Los Angeles classification of reflux esophagitis. Reflux esophagitis was more severe in the TEG group than in the CEG group, while there was no difference in the grading of reflux pharyngolaryngitis between the two groups. The pharyngolaryngeal symptoms and F-scale scores were not correlated with the severity of reflux pharyngolaryngitis in each group. The grading of reflux pharyngolaryngitis and that of reflux esophagitis was correlated in each group (P<0.001 in the CEG group and P=0.002 in the TEG group). We proposed a new endoscopic classification of reflux pharyngolaryngitis. The new classification of reflux pharyngolaryngitis correlated fairly well with the Los Angeles classification of reflux esophagitis, although this classification did not correlate with the clinical symptoms in patients who underwent esophagectomy. Follow-up attention including upper endoscopy should be paid to reflux pharyngolaryngitis in patients after esophagogastrostomy as well as reflux esophagitis, because there is often a lack in symptoms regardless of high incidence of pharyngolaryngitis.

Reflux esophagitis and columnar-lined esophagus after cervical esophagogastrostomy (following esophagectomy).

Reflux esophagitis (RE) and columnar-lined esophagus (CLE) are frequently observed after esophagectomy. The incidence of these conditions according to time and to the route of esophageal reconstruction after esophagectomy remains unknown. The aim of this study was to clarify any changes and differences of the incidence of RE and CLE in patients who underwent gastric tube reconstruction after esophagectomy. A hundred patients who underwent cervical esophagogastrostomy after resection of the thoracic esophagus were included in this study. We reviewed their endoscopic findings at 1 month, at 1 year and at 2 years after surgery, and compared the incidence rates of RE and CLE with the passage of time and among the three reconstruction routes; a subcutaneous route, a retrosternal route, and a posterior mediastinal route. The incidence rate of RE was 42%, 37% and 38%, at 1 month, 1 year and at 2 years after surgery, respectively. There was no significant difference in the incidence of RE according to the time after surgery. The incidence rate of severe RE (Grade C and D in the Los Angeles Classification) was 9% percent at 1 month after surgery, 18% at 1 year after surgery and 22% at 2 years after surgery, significantly increasing with passage of time. The incidence rate of CLE was 0% at 1 month after surgery, 14% at 1 year after surgery and 40% at 2 years after surgery, significantly increasing with passage of time. No difference was observed in the incidence of RE and that of CLE among the three routes of esophageal reconstruction. Severe RE and CLE increase with passage of time after cervical esophagogastrostomy. Therefore, careful endoscopic follow-up is necessary for such patients irrespective of the route of esophageal reconstruction.

Gingipains in the culture supernatant of Porphyromonas gingivalis cleave CD4 and CD8 on human T cells.

Porphyromonas gingivalis has been shown to attack host defense systems through proteolytic cleavage of a wide variety of members of the systems. In this study, we examined the ability of P. gingivalis culture supernatant to alter the expression of human T cell surface proteins. As judged by flow cytometric analysis, detection of CD4 expression was completely eliminated by the supernatant, but CD8 was less sensitive. When the culture supernatant was added with reducing agents, proteolytic activity was enhanced, resulting in the cleavage of CD8. Mitogenic response of T cells to phytohemagglutinin or concanavalin A was decreased by the treatment of the cells with the culture supernatant of P. gingivalis. The three forms of gingipains (high molecular mass arginine-specific gingipain, arginine-specific gingipain 2 and lysine-specific gingipain) purified from the culture supernatant of P. gingivalis actively cleaved CD4 and CD8 on human T cells, indicating that proteolytic activity of the culture supernatant was due to gingipains. These results suggest that cysteine proteinases like gingipains released from P. gingivalis cleave T cell surface proteins and impede T cell function.

[Experimental gene therapy using p21/WAF1 gene in esophageal squamous cell carcinoma--adenovirus infection and gene gun technology].

p21/WAF1 (p21) inhibits the activity of the cyclin/cdk complex and controls the G1 to S cell phase transition. In the present study, we used a recombinant adenoviral approach and gene gun technology to introduce p21 into esophageal cancer cells in order to assess the effect of p21 on cell growth. Infection with the p21 adenovirus (AdV) using gene gun technology resulted in inhibition of TE9 and KE3 cell growth. The levels of involucrin, which is a marker of squamous epithelium differentiation, markedly increased at 48 h and 72 h after p21 AdV infection in TE9 cells. These results indicate that p21 plays an important role in esophageal cancer cell proliferation. Overexpression of the p21 gene can inhibit cell growth and induce differentiation in esophageal cancer cells. p21 gene therapy may prove beneficial in the treatment of esophageal cancer.