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Background: After esophagectomy for esophageal and esophagogastric cancer, more than half of patients have lost > 10% of their body weight at 12 months. In most cases, the gastric remnant is used for reconstruction after esophagectomy. One of the most serious nutritional complications of this technique is delayed gastric emptying caused by gastric remnant mobilization and denervation of the vagus nerve. The aim of the PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy (PYNI-GAREREO) trial is to analyze the clinical outcome of modified Horsley pyloroplasty (mH-P) as a method of preventing delayed gastric emptying., Methods: The PYNI-GAREREO trial is designed as an open randomized, single-center superiority trial. Patients will be randomly allocated to undergo gastric remnant reconstruction with mH-P (intervention group) or no intervention (control group) in parallel groups. All patients with esophageal cancer or esophagogastric cancer planning to undergo curative minimally invasive esophagectomy will be considered for inclusion. A total of 140 patients will be included in the study and randomized between the groups in a 1:1 ratio. The primary outcome is the body weight change at 6 months postoperatively, and the secondary outcomes are the nutritional status, postoperative complications, functional outcome, and quality of life until 1 year postoperatively., Discussion: We hypothesize that mH-P after minimally invasive esophagectomy more effectively maintains patients' nutritional status than no pyloroplasty., Trial Registration: UMIN Clinical Trials Registry UMIN000045104. Registered on 25 August 2021. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051346 ., (© 2023. The Author(s).)

Background and Aim: The esophageal triamcinolone acetonide (TA)-filling method is a novel local approach for stenosis prevention after extensive esophageal endoscopic submucosal dissection (ESD). We evaluated this method after subcircumferential ESD., Methods: We enrolled 20 patients with esophageal cancer requiring subcircumferential ESD in a prospective multicenter study. Esophageal TA filling was carried out 1 day and 1 week after ESD, with follow-up endoscopy every 2 weeks. We treated severe stenosis preventing endoscope passage with endoscopic balloon dilatation (EBD) and additional TA filling, and mild stenosis allowing endoscope passage with additional TA filling only. Primary endpoint was incidence of severe stenosis; secondary endpoints were total number of EBD, rate of additional TA filling, time to stenosis and complete re-epithelialization, dysphagia score, and adverse events. Horizontal resection grade was divided into grades 1 (≥ 9/12 and <10/12 of the circumference), 2 (≥ 10/12 and <11/12), and 3 (≥ 11/12 but not circumferential) and analyzed statistically for correlation with endpoints., Results: Incidence of severe stenosis was 5.0% (1/20; 0.1-24.8%) and was treated with three EBD. Six patients showed mild stenosis. Additional TA filling was carried out in these seven patients: 0% (0/9) for grade 1 resection, 40% (2/5) for grade 2, and 83% (5/6) for grade 3 (P < 0.05). Median time to stenosis and re-epithelialization was 3 and 7 weeks, respectively. Dysphagia score deteriorated in one patient. No adverse events occurred., Conclusions: The esophageal TA-filling method prevented stenosis after subcircumferential ESD. Grade ≥2 resection showed a high risk for stenosis, but additional TA filling for mild stenosis inhibited stenosis progression (UMIN000024384)., (© 2019 Japan Gastroenterological Endoscopy Society.)

Background: Barrett's esophagus (BE) is a known precursor for development of esophageal adenocarcinoma and surveillance of affected patients is necessary when cancer progression risk is considered to be high. However, the accuracy of BE diagnosis may not be homogenous among institutions with endoscopy units. We investigated inter-institutional variability by examining the accuracy of endoscopic diagnosis of BE at 4 different hospitals., Methods: The accuracy of BE diagnosis at the 4 hospitals was retrospectively reviewed by 6 expert endoscopists, who independently reviewed endoscopic images of approximately 500 consecutive patients examined at each hospital without information regarding the diagnosis by the on-site endoscopists. When the expert reviewers made different diagnosis, a final diagnosis was made by consensus. That was then compared with the diagnosis of the attending endoscopists at each hospital and their concordance was calculated separately for each endoscopy unit. In addition, the relationship between diagnostic accuracy and endoscopic experience was assessed., Results: The prevalence of BE diagnosis by the on-site endoscopists was not homogenous and varied widely (17.2-96.8%). In 1 hospital, over-diagnosis was the cause of dissimilarity, while under-diagnosis was the cause in two hospitals. Diagnostic accuracy by the attending endoscopists in all 4 hospitals ranged from 44.6 to 83.1% (P < 0.05). There was no significant association between diagnostic accuracy and endoscopic experience or board licensing status of the on-site endoscopists., Conclusion: Diagnostic accuracy for BE was not homogenous among 4 hospitals, and problems related to over- and under-diagnosis should be considered.

Background: Esophageal adenocarcinoma (EAC) is frequently found on the right-anterior wall of the distal esophagus in short-segment Barrett's esophagus (SSBE) patients. However, the endoscopic characteristics of EAC in cases with long-segment BE (LSBE) and squamous cell carcinoma (ESCC) in the lower esophagus remain to be fully evaluated. Here, we determined the circumferential distribution and clinical characteristics of esophageal cancer occurring in the lower esophagus based on histological subtype., Methods: We retrospectively reviewed the medical records of 150 patients with esophageal cancer (ESCC, n = 100; EAC, n = 50) diagnosed at our hospital or a related facility between January 2002 and June 2017, including information regarding endoscopic findings, etiology, and clinical parameters., Results: Of the 100 patients with ESCC, 28 lesions were located in the lower esophagus, though characteristic circumferential distribution was not seen regardless of location. Those showed a greater frequency of smoking and drinking habit and gastric mucosal atrophy as compared to patients with EAC. Consistent with the previous reports, EAC in SSBE (n = 41) was frequently located on the right-anterior wall. Likewise, EAC at the esophagogastric junction (EGJ) in LSBE was frequently located on the right-anterior wall, while EAC distant from the EGJ showed no characteristic circumferential distribution., Conclusion: Our results showed no circumferential predilection for ESCC in the lower esophagus, suggesting that development of this type of lesion may be less affected by gastroesophageal reflux. In addition, EAC at the EGJ was frequently found on the right-anterior wall irrespective of BE length.

Background and Aims: Endoscopic submucosal dissection (ESD) for extensive esophageal carcinomas may cause severe stenosis requiring endoscopic balloon dilations (EBDs). A standard prevention method has not been established. We propose the esophageal triamcinolone acetonide (TA)-filling method as a novel local steroid administration procedure., Methods: We enrolled 22 consecutive patients with early esophageal cancer who were treated using either subcircumferential or circumferential ESD (15 and 7 procedures, respectively) in this case series. Esophageal TA filling was performed on the day after ESD and 1 week later and was performed again if mild stenosis was found on follow-up. EBD with TA filling was performed only for severe stenosis that prevented endoscope passage. The primary endpoint was the incidence of severe stenosis. Secondary endpoints were the total number of EBDs and additional TA filling, dysphagia score, time to stenosis and to complete re-epithelialization, and any adverse events., Results: The incidence of severe stenosis was 4.5% (1/22; confidence interval, .1%-22.8%), and EBD was performed 2 times in 1 patient. Mild stenosis was found in 9 patients. Additional TA filling was performed in 45.5% of patients (10/22; median, 5 times; range, 1-13). The dysphagia score deteriorated to 1 to 2 in 31.8% (7/22) but showed a final score of 0 after complete re-epithelialization in 90.9% (20/22). The median time to stenosis was 3 weeks (range, 3-4) and that to complete re-epithelialization was 7 weeks (range, 4-36). No severe adverse events occurred., Conclusions: The esophageal TA-filling method is highly effective for preventing severe stenosis after extensive esophageal ESD., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aim: The incidence of esophageal adenocarcinoma (EAC) in cases with long-segment Barrett's esophagus (BE) has not been investigated in Japan. The aim of this study is to investigate the incidence of EAC in Japanese cases with long-segment BE prospectively., Methods: This is a multicenter prospective cohort study investigating the incidence rate of EAC in patients with BE with a length of at least 3 cm. Study subjects received index esophagogastroduodenoscopy at the time of enrollment, and they were instructed to undergo yearly follow-up esophagogastroduodenoscopy. Patients in whom EAC was diagnosed in the endoscopic examinations underwent subsequent treatment, and their prognosis was observed., Results: Of 215 enrolled patients, six (2.8%) were initially diagnosed with EAC at the enrollment. Among the remaining 209 patients, 132 received at least one follow-up esophagogastroduodenoscopy. In this follow-up, three EACs developed in 251 observed patient-years (incidence rate: 1.2% per year). Most of the EACs detected at the initial endoscopic examination (5/6, 83%) were already at advanced stages. Meanwhile, all the three lesions detected in the follow-up esophagogastroduodenoscopies were identified as early cancers and subjected to curative resection., Conclusions: The incidence rate of EAC in Japanese cases with long-segment BE was calculated to be 1.2% in a year., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The classification of Barrett esophagus (BE) using magnifying endoscopy with narrow band imaging (ME-NBI) is not widely used in clinical settings because of its complexity. To establish a new simplified available classification using ME-NBI.We conducted a cross-sectional study in a single-referral center. One hundred eight consecutive patients with BE using ME-NBI and crystal violet (CV) chromoendoscopy, and histological findings were enrolled. BE areas observed by ME-NBI were classified as type I or II on the basis of capillary pattern (CP), and as closed or open type on the basis of a mucosal pit pattern using CV chromoendoscopy; then, biopsy samples were obtained. We evaluated the relation between CP and pit pattern, expression of the factors with malignant potential, percentage of microvascular density, and interobserver agreement.One hundred thirty lesions from 91 patients were analyzed. Type II CP had more open type pit pattern areas and significantly greater microvascular density than type I. The presence of dysplasia, specialized intestinal metaplasia, expressions of COX-2, CDX2, and CD34, and PCNA index were significantly higher in type II, whereas the multivariate analysis showed that type II was the best predictor for the presence of dysplasia (OR 11.14), CD34 expression (OR 3.60), and PCNA (OR 3.29). Interobserver agreement for this classification was substantial (κ = 0.66).A simplified CP classification based on observation with ME-NBI is presented. Our results indicate that the classification may be useful for surveillance of BE with high malignant potential.

Purpose: This study investigated the diagnostic accuracy of hybrid positron-emission tomography/computed tomography (PET/CT) for lymph node (LN) metastasis of esophageal cancer. We also investigated the correlation between the size of metastatic nests and the detection by PET/CT., Methods: Two hundred and fifty-eight patients with esophageal squamous cell carcinoma who underwent esophagectomy with two- or three-field radical lymphadenectomy were analyzed retrospectively. We compared the diagnosis of preoperative PET/CT to the postoperative histopathological examination by each anatomical field (n = 1,231) in all 258 patients. The metastatic LNs resected from PET/CT positive fields were classified as belonging to the PET/CT-N-positive group (n = 229) and those from negative fields as belonging to the PET/CT-N-negative group (n = 352). The cross-sectional areas of metastatic nests were measured in each metastatic LN., Results: Of the 1,231 fields, 275 (22 %) were positive for metastasis, including 581 LNs from 408 regional LN stations. The sensitivity and specificity of PET/CT examined by each anatomical field were 25.8 and 97.8 %, respectively. The median area of metastatic nests was 17.7 mm2 in the PET/CT-N-positive group, and 7.7 mm2 in the PET/CT-N-negative group (p < 0.001)., Conclusions: A significant correlation was suggested between the nest size and detection by PET/CT. Because of its low sensitivity, PET/CT alone is insufficient to determine the surgical procedures, especially when considering reduction surgery.

The prevalence rates of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) arising from BE show striking geographic patterns as they are much more common in Western as compared with Asian countries. However, recent epidemiological studies indicate that the number of patients with BE and EAC are gradually increasing in Asia including Japan, corresponding to the increase in prevalence of gastroesophageal reflux disease (GERD). Because the prognosis of patients with advanced-stage EAC remains poor, early detection of neoplastic lesion in those with BE has led to recent interest in effective treatment. Several promising studies have revealed that early neoplasia in BE is mainly located in the right anterior wall of the distal esophagus. Interestingly, this endoscopic characteristic has been found in both Western and Japanese populations. Potential pathophysiologic explanations underlying the circumferential distribution of neoplasia in BE include a nonuniform asymmetric distribution of esophageal acid exposure, with a tendency toward mucosal acid-related injury on the right side of the esophageal wall in patients with GERD, and the functional structure of the lower esophageal sphincter. Findings of the present study should improve lesion detection and aid in developing a target biopsy protocol for surveillance of BE., (© 2014 S. Karger AG, Basel.)

Cdx2 expression in esophageal stem cells induced by reflux bile acids may be an important factor for development of Barrett's esophagus, whereas Notch signaling is a molecular signaling pathway that plays an important role in the determination of cell differentiation. ATOH1 (a factor associated with Notch signaling) plays an important role in differentiation of stem cells into goblet cells. However, the relationship between the Notch signaling pathway and Cdx2 expression in the development of Barrett's esophagus has not been explored. The aim of this study was to investigate the interrelationship between Notch signaling and Cdx2 in esophageal epithelial cells. The expressions of Cdx2, MUC2, and intracellular signaling molecules related to Notch signaling (Notch1, Hes1, and ATOH1) were examined using real-time polymerase chain reaction (PCR) and immunohistochemical staining with biopsy specimens obtained from esophageal intestinal metaplasia (IM) with goblet cells (IM⁺) and columnar epithelium not accompanied by goblet cells (IM⁻). For in vitro experiments, we employed human esophageal epithelial cell lines (OE33, OE19, and Het-1A). After forced Cdx2 expression by applying a Cdx2 expression vector to the cells, changes in the expressions of Notch1, Hes1, ATOH1, Cdx2, and MUC2 were analyzed by real-time PCR and western blot analysis. Changes in expressions of Notch1, Hes1, ATOH1, Cdx2, and MUC2 in cells were analyzed following stimulation with bile acids in the presence or absence of Cdx2 blocking with Cdx2-siRNA. Suppressed Hes1 and enhanced ATOH1 and MUC2 expressions were identified in IM⁺ specimens. Forced expression of Cdx2 in cells suppressed Hes1, and enhanced ATOH1 and MUC2 expressions, whereas bile acids suppressed Hes1, and enhanced ATOH1, Cdx2, and MUC2 expressions. On the other hand, these effects were blocked by siRNA-based Cdx2 downregulation. Enhanced expression of Cdx2 by stimulation with bile acids may induce intestinal differentiation of esophageal columnar cells by interaction with the Notch signaling pathway.

Activation-induced cytidine deaminase (AID) induces somatic mutations in various host genes of non-lymphoid tissues, thereby contributing to carcinogenesis. We recently demonstrated that Helicobacter pylori infection and/or proinflammatory cytokine stimulation triggers aberrant AID expression in gastric epithelial cells, causing mutations in the tumour-suppressor TP53 gene. The findings of the present study provide evidence of ectopic AID expression in Barrett's oesophagus and Barrett's oesophageal adenocarcinoma, a cancer that develops under chronic inflammatory conditions. Immunoreactivity for endogenous AID was observed in 24 of 28 (85.7%) specimens of the columnar cell-lined Barrett's oesophagus and in 20 of 22 (90.9%) of Barrett's adenocarcinoma, whereas weak or no AID protein expression was detectable in normal squamous epithelial cells of the oesophagus. We validated these results by analysing tissue specimens from another cohort comprising 16 cases with Barrett's oesophagus and four cases with Barrett's adenocarcinoma. In vitro treatment of human non-neoplastic oesophageal squamous-derived cells with sodium salt deoxycholic acid induced ectopic AID expression via the nuclear factor-kappaB activation pathway. These findings suggest that aberrant AID expression occurs in a substantial proportion of Barrett's epithelium, at least in part due to bile acid stimulation. Considering the genotoxic activity of AID, our current findings suggest that aberrant AID expression might enhance the susceptibility to genetic alterations in Barrett's columnar-lined epithelial cells, leading to cancer development.

Goals: To investigate the relationship between fatty acid synthase (FASN) expression and the clinicopathological characteristics of Barrett's esophagus and its carcinogenesis., Background: FASN, a key enzyme of the fatty acid biosynthetic pathway, is overexpressed not only in various types of cancer, but also in premalignant conditions. Therefore, FASN overexpression is considered to be indicative of a possible premalignant stage., Study: Patients (N=354) with endoscopically and histologically proven Barrett's esophagus were enrolled. Mucin phenotyping of Barrett's esophagus, expression of FASN and COX-2, cellular proliferation, and apoptosis were evaluated immunohistochemically in biopsy samples, and factors influencing FASN expression were determined by multivariate logistic regression analysis. To evaluate if gastric reflux induces FASN expression, esophageal adenocarcinoma cells were treated with bile acid and low pH, and the effect of a FASN inhibitor on cell proliferation was assessed., Results: Expression of FASN protein was observed in 52.2% of patients with Barrett's esophagus by immunohistochemistry; this expression pattern was retained in esophageal adenocarcinoma. Intestinal mucin phenotype, COX-2, increased stromal angiogenesis, and elevated proliferating cell nuclear antigen index were confirmed to be positive independent factors for FASN expression. In the esophageal adenocarcinoma cell line SEG-1, FASN mRNA was induced by bile acid with low pH. Cell proliferation was strongly suppressed by the FASN inhibitor C75., Conclusions: FASN is strongly expressed in the intestinal mucin phenotype of Barrett's esophagus, in which Barrett's glandular cells display elevated cellular proliferation, angiogenesis, and COX-2 expression. Exposure of the lower esophagus to bile acid with low pH may induce FASN in Barrett's esophagus.

We retrospectively evaluated the efficacy and safety of a first-line combination chemotherapy with Docetaxel, Cisplatin, and 5-fluorouracil (DCF therapy) in nine patients with advanced esophageal cancer. Dose administrated were 75 mg/m² of Docetaxel on day 1, 75 mg/m² of CDDP on day 1, and 750 mg/m² of 5-FU on day 1-5. Complete response (CR) in two patients (22. 2%), partial response (PR)in three patients ( 33. 3%), and no change (NC) in four patients (55. 6%) were shown for main lesions, while CR in one (11. 1%), PR in five (55. 6%), and NC in three (33. 3%) were shown for lymph node metastases. Response rates of the DCF therapy were 55. 6% for main lesions and 66. 7% for lymph node metastases. Five patients who achieved PR or CR underwent esophagectomy with lymph node dissection. Toxicity from DCF therapy was grade 3 or 4 emergent adverse events (77. 8% of neutropenia, 55. 6% of febrile neutropenia, and 55. 6% of anorexia). DCF therapy improved the response rate in esophageal cancer patients, but resulted in some increase in toxicity. Prospective study with prevention of toxicity should be planned in order to evaluate first-line DCF therapy for advanced esophageal cancer.

Communicating bronchopulmonary-foregut malformation, a variant of bronchopulmonary sequestration, is a rare anomaly characterized by communication between an isolated portion of the respiratory tree and the gastrointestinal tract. We report herein a unique case involving a 43-year-old man with squamous cell carcinoma arising in communicating bronchopulmonary-foregut malformation. This patient had a workup for a chief complaint of exacerbation of constitutional dysphagia, resulting in detection of squamous cell carcinoma involving the lower esophagus. Under the clinical diagnosis of esophageal carcinoma, esophagectomy was performed after neoadjuvant chemoradiotherapy. Pathologic findings showed that squamous cell carcinoma had arisen in malformed bronchopulmonary tissue constituting part of the distal esophagus segmentally. This case was unique in that squamous cell carcinoma developed in an extremely rare type of congenital abnormality that had functioned as a passageway for food from birth, as a result of chronic irritation for more than 4 decades., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: The purpose of this retrospective study was to investigate the feasibility of colon interposition procedures after esophagectomy with extended lymphadenectomy., Methods: Between 1990 and 2008, 95 consecutive patients underwent colon interposition after esophagectomy with extended lymphadenectomy for esophageal cancer in our Institution. We reviewed clinical data and long-term survival, and also investigated the association between anastomotic leakage and clinicopathologic findings., Results: We applied three-field lymphadenectomy to 71 patients and two-field to 24 patients, by a right thoracotomy. Ninety-two patients underwent reconstruction by a retrosternal route, and a posterior mediastinal route was applied to only three patients. We performed hand-sewn anastomosis in the neck in all cases. Three patients required microvascular surgery. Sixty-one patients (64%) experienced postoperative morbidity, most commonly pulmonary complications. Anastomotic leakage occurred in 12 patients (13%). No colon conduit necrosis was detected. Overall mortality, including hospital mortality, was 5.3%. Dysphagia (39%) and diarrhea (38%) were common and stricture was low (6%) after discharge. The overall 5-year survival rate was 43%. During the latter period (1998 to 2008), when ileocolon grafts evolved as the primary choice for interposition, the rate of leakage decreased from 17% (1990 to 1997) to 5.4%. No mortality was recorded during the latter period., Conclusions: Results from this study demonstrate that colon interposition after esophagectomy with extended lymphadenectomy is feasible and can have a favorable outcome.

Despite many positive reports on video-assisted esophagectomy (VAE) for malignant esophageal tumors, VAE remains a lesser used procedure in Japan because of its technical difficulty and the strong desire of esophageal surgeons for thorough lymphadenectomy. In this article, we review former reports as well as our own experiences to demonstrate the feasibility and rationale for radical VAE as a standard operation for esophageal cancer. Although the reduction of surgical stress is not clear, it has been reported that VAE is associated with lower morbidity related to postoperative pulmonary complications, and we experienced a shorter period of postoperative systemic inflammatory response syndrome. VAE is advantageous not only because it is less invasive but also because of the possibility of a more meticulous operation through the magnifying effect of the surgical field and the alteration of the viewpoint of the surgeon. The number of dissected lymph nodes, a possible indicator of the extensiveness and thoroughness of lymphadenectomy, is reported to be the same for VAE as for conventional thoracotomy by many surgeons, and our experience was no exception. Although it is too early to discuss the prognostic effect, no obvious disadvantage in prognosis has been reported. We are convinced that radical VAE is not inferior in radicality as an operation for esophageal cancer. As the evaluation of radicality and safety of radical VAE differs somewhat from surgeon to surgeon, different attitudes about the indications for radical VAE remain. We cautiously suggest that use of this new procedure should move forward.

Three months after esophagectomy for esophageal cancer, a 58-year-old man presented with fluid trapped in his upper mediastinum due to chylous leakage from a duplicated left-sided thoracic duct that remained after excision of the main thoracic duct. Classical lymphangiography using lipiodol confirmed the presence of duplicated thoracic ducts. Conservative treatments were not effective, and then we performed ligation of the left-sided thoracic duct with left-sided video-assisted thoracoscopic surgery. Anatomic variations of the thoracic duct can result in chylous leakage after thoracic surgery. Even if the patient has anomaly of the thoracic duct, classical lymphangiography is useful for detecting locations of the thoracic duct precisely, allowing for certain ligation of the duct with video-assisted thoracoscopic surgery.

The combination chemotherapy with docetaxel/CDDP/5-FU(DCF)for head and neck squamous carcinoma(SCC) has been widely accepted. It seems quite natural that DCF therapy is expected to be equally effective against esophageal SCC because of their histological similarity. In this report, we present a case of unresectable advanced esophageal SCC with multiple liver metastases which showed remarkable regression by DCF therapy, with relatively slight adverse effects. The patient was a 46-year-old female, who underwent upper gastrointestinal fiber-optic endoscopy for dysphasia and was diagnosed to have upper middle thoracic esophageal SCC. Abdominal CT scan showed multiple liver metastases with para-aortic lymph node involvement. The clinical stage diagnosis was T3N4M1, Stage IVB, obviously non-resectable far-advanced esophageal SCC. Systemic chemotherapy with DCF was started as the initial treatment. The chemotherapy regimen was as follows. 5-FU 500 mg/m(2) was administered as continuous intravenous infusion through day 1 to 5, while docetaxl 60 mg/m(2) and cisplatin 50 mg/m(2) were given intravenously on day 2. Each course was followed by a 23-day drug-free period, and the entire course was repeated every 28 days. Ten cycles of this DCF chemotherapy were carried out. After 4 cycles, primary lesion was judged as complete response(CR)by endoscopy. After 8 cycles, the liver metastases were judged as CR and para-aortic lymph nodes showed a partial response(PR)by CT scan. After 10 cycles, all we could detect was a small local recurrence of the primary tumor, which was then treated with chemoradiotherapy at the outpatient clinic. Until this writing, we added 2 more cycles of DCF therapy for the recurrent para-aortic and inguinal lymph node metastasis. Three years have passed from her first visit, and the patient is still in a stable disease state. The adverse effects were grade 3 at most in both hematological and non-hematological toxicity. We conclude that DCF therapy is potentially very effective for advanced esophageal SCC.

Background and Aim: Acid suppressive therapy has been reported to regress Barrett's esophagus. However, it is still controversial as to whether all Barrett's esophagus patients respond to this therapy. The factors that might facilitate newly developed squamous re-epithelialization after biopsy excision of Barrett's mucosa were evaluated to identity individuals who may favorably respond to the regression therapy., Methods: Two hundred and forty-seven biopsy sites from 185 patients with Barrett's esophagus were examined by endoscopy to investigate possible squamous re-epithelialization of Barrett's mucosa after endoscopic biopsy. Before endoscopic examination, all participants were requested to answer questionnaires concerning sociodemographic characteristics, lifestyle habits and drugs usage. The mucin phenotype, Cdx2 expression, cyclooxygenase-2 expression, cellular proliferation and apoptosis of Barrett's mucosa were immunohistochemically investigated in the biopsy samples taken from Barrett's esophagus. The influence of these factors on the newly developed squamous re-epithelialization of Barrett's mucosa after endoscopic biopsy excision was evaluated., Results: By multivariate analysis, the independent factors that favored squamous re-epithelialization were the gastric mucin predominant phenotype of Barrett's mucosa and the absence of Cdx2 protein expression. In Barrett's mucosa with the gastric predominant mucin phenotype, proton pump inhibitor administration, the absence of reflux esophagitis and a low proliferating cell nuclear antigen index were found to be independent predictors for squamous re-epithelialization., Conclusions: The absence of the intestinal predominant mucin phenotype was a positive predictor for newly developed squamous re-epithelialization at the site of biopsy of Barrett's mucosa. Only Barrett's esophagus with the gastric predominant mucin phenotype may predict a favorable response to acid suppressive therapy.

A study of 256 patients whose dates and patterns of first mode of recurrence after curative esophagectomy from 1984 to 2004 revealed the recent improvement in survival after the detection of tumor recurrence. This tendency was evident in lymphatic recurrence, particularly in the cervical area. Lung metastasis was another mode of recurrence that has shown recent improvement. In this series, 20 patients with lymph node metastases underwent reoperation for local or regional tumor control. The addition of systemic chemotherapy or chemoradiotherapy was our general rule. The 5-year survival rate after the detection of tumor recurrence in these 20 patients was 47.4%. Six with lung metastases in the group of patients whose esophagectomies were performed in the last 7 years underwent video-assisted pulmonary tumor resection. Five patients in this group are alive without signs of further recurrence for 92 to 1,437 days. The early detection of recurrent tumor, vigorous attempts to achieve locoregional control, and the addition of systemic chemotherapy are all important in achieving better results. We routinely perform conventional cervical and abdominal ultrasonography and computed tomography every 6 months until 6 years after surgery is performed.

The lymph node metastases of esophageal cancer occur over a wide area. It is essential for radical surgery of such metastases to aim at en bloc dissection. Otherwise, it can easily become a combination of blunt esophagectomy and lymph node sampling through a right thoracotomy. In the intrathoracic procedure, all the nodes to be dissected can be harvested while attached to the esophagus together with the surrounding connective tissue, except for the pretracheal nodes in front of the cardiac branches of the right vagus nerve and the subaortic arch nodes. It is important to dissect the left paratracheal nodes en bloc, preserving the left recurrent laryngeal nerve. In the abdomen, nodes around the celiac axis and nodes on the common hepatic artery and proximal part of the splenic artery are all removed en bloc with the perigastric nodes in the left gastric arterial basin. The cervical paratracheal and paraesophageal nodes are removed separately from the resected esophagus, but the continuity of dissection can be ensured when the dissection from the neck meets the empty space made by the dissection along the bilateral recurrent laryngeal nerves through the thoracotomy. We believe that such en bloc dissection is the key to improving the long-term results of esophageal cancer surgery.

For patients who have esophageal carcinoma with tracheal invasion surgery is usually not indicated because operative complications are considerable and the prognosis is poor. We experienced complete regression of a large esophageal carcinoma with tracheal stenosis due to tumor invasion without tracheo-esophageal fistula. Irradiation of 68 Gy was delivered to a long T field from the neck to the lower thoracic esophagus, and was combined with chemotherapy using cisplatin and 5-fluorouracil. The tumor decreased markedly in size and the tracheal stenosis resolved. The patient has survived for 4 years, although second primary early esophageal carcinoma and hypopharyngeal carcinoma were detected 2 years after his initial chemoradiotherapy. Although the prognosis of advanced esophageal carcinoma with invasion of other organs is usually poor, the effect of chemoradiotherapy can sometimes be dramatic and a good result can be achieved in such patients.

The growth of human cancer cells expressing peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been reported to be inhibited by PPAR-gamma ligands. In esophageal squamous-cell carcinoma cell lines T.T, T.Tn, and EC-GI-10, we detected expression of PPAR-gamma and investigated the effects of PPAR-gamma ligands on these cell lines in vitro with the use of troglitazone, pioglitazone, and 15d-PGJ2. Marked growth inhibition by the PPAR-gamma ligands was observed in all cases. The growth-inhibitory effect was evidenced by a dose-dependent inhibition of deoxyribonucleic acid synthesis and was associated with altered cell-cycle progression manifesting G1 arrest. Cell-cycle arrest in T.Tn cells induced by troglitazone could be correlated with an increased level of cyclin-dependent kinase inhibitor p27(Kip1), p21(Cip1/Waf1), and p18(Ink4c). Moreover, troglitazone treatment increased the expression of interleukin-1 alpha, a multifunctional cytokine implicated in antitumor immunity. These findings suggest that troglitazone and other PPAR-gamma ligands have adjuvant or neoadjuvant therapeutic potentials in esophageal cancer.

Background: A retrospective investigation was conducted to determine whether autologous blood collection could reduce allogenic transfusion after resection of esophageal cancer and whether allogenic transfusion influenced postoperative infection., Methods: Patients (n = 100) who met the criteria for hemoglobin, age, body weight, and serum protein donated 800 mL of autologous blood from May 1994 to December 1997. The control group (n = 248) was selected from patients who met the same criteria and did not donate autologous blood over the 10 years before the start of autologous blood collection., Results: Only three patients (3%) from the autologous group required allogenic transfusion versus 84 patients (33.7%) from the control group. Sixteen of the 26 patients who received more than 4 units of allogenic blood contracted postoperative infections compared with 25 of 165 patients who did not (P < .0001). Autologous blood transfusion significantly increased the probability of avoiding allogenic transfusion (odds ratio, 27.58), and allogenic transfusion was significantly related to postoperative infection (odds ratio, 1.19), according to logistic regression analysis., Conclusions: Autologous blood collection reduces the need for allogenic transfusion in patients undergoing resection of esophageal cancer, and avoidance of allogenic transfusion may reduce the risk of postoperative infection.

We attempt to clarify the problems of pulmonary thromboembolism (PTE), which occurs less frequently in Japan than in the West, regarding its special perioperative management and prophylaxis for PTE after esophagectomy. We studied 26 patients with PTE following esophagectomy among 1023 patients with esophageal cancer between 1984 and 1997. The presence of embolism was confirmed by pulmonary perfusion scintigraphy. The incidence, diagnosis, and other issues of PTE were all reviewed. The incidence of PTE was 2.5%, with patients showing a biphasic early and late onset. The main symptoms were dyspnea in 19 patients and tachycardia in 17. Scintigraphy demonstrated 154 lesions, 35.7% of which were located in the left lower lobe and 25.3% in the right lower lobe. Treatment mainly consisted of the administration of heparin and urokinase. Four of the 26 patients died. Intermittent pneumatic compression (IPC) with the administration of heparin has been used in our department since 1994 to prevent PTE and this has also helped to decrease the incidence from 3.2% to 0.7%. Because the incidence of PTE following esophagectomy is higher than expected, PTE should be considered whenever hypoxemia of some unknown cause is found. Both early diagnosis and treatment are essential. It is also important to prevent PTE by the use of IPC.

The therapeutic strategy for adenocarcinoma in Barrett's esophagus is discussed based on a comparison with squamous cell carcinoma. The pattern and range of lymph node metastasis of adenocarcinoma in Barrett's esophagus is similar to that of squamous cell carcinoma, as is the pattern of recurrence. Chemotherapy is less effective, except for some reports on paclitaxel, but chemoradiation therapy is comparable in effect. The general tendency of a better prognosis for patients with carcinoma in Barrett's esophagus is the result of several factors, such as earlier detection of the disease, lower probability of lymph node metastasis, and distal location which permits less radical curative surgical procedures without cervical and superior mediastinal lymph node dissection. In principal the therapeutic strategy for adenocarcinoma in Barrett's esophagus should be determined like that for squamous cell carcinoma, taking into account the location of the lesion and the depth of invasion.

We report on the problems of diagnosis and surgical technique from the standpoint of mediastinal anatomy in patients with esophageal cancer and right aortic arch associated with a vascular ring. We propose that left thoracotomy plus sternotomy is the best approach to allow visualization of the bilateral recurrent laryngeal nerves.

For thoracic esophageal cancer, we perform extended three field lymph node dissection, and have achieved nearly 50% of overall 5-year survival. However, patients sometimes develop lymph node recurrences in spite of having no lymph node metastases found by conventional histopathologic examination. In a patient with esophageal squamous cell carcinoma, we sequenced all the p53 cDNA translated regions (exon 2-10) of primary carcinoma, and confirmed one p53 nonsense mutation in exon 10. Then we extracted genomic DNA from 150 surgically dissected lymph nodes from that patient, and performed polymerase chain reaction analysis (PCR-RFLP) to detect the same p53 mutation in the lymph nodes. PCR-RFLP analysis showed the same p53 mutation in six lymph nodes. One node was located along the right recurrent laryngeal nerve, where no positive nodes was identified by conventional histopathologic examination. The p53 mutational diagnosis of metastatic cancer may be useful in detecting minimal residual disease.

Carcinosarcoma of the esophagus includes both carcinomatous and sarcomatous elements. The classification and histogenesis of carcinosarcoma is controversial. In a polypoid carcinosarcoma diagnosed in a resected esophagus the sarcomatous component was composed of dense interlacing bundles of spindle-shaped cells in the submucosa. Areas with transitional features between the two components were observed. Immuno-histochemical examination showed vimentin-positive cells in the sarcomatous areas. Subsequently, obtained autopsy specimens from the lung, kidney and iliac bone showed metastatic osteosarcoma composed of an interlacing pattern of bone or osteoid components. We suspected that the sarcomatous elements in the esophagus resulted from sarcomatous transformation of carcinoma cells, and that the metastatic lesions showed differentiation of neoplastic cells to the osteosarcoma.

We discussed the rational extent of the lymph node dissection for carcinoma of the lower third of the esophagus of T2 or T3 stage with abdominal lymph node metastasis. Lymph node metastasis developed in 89.5% of patients. Cervical lymph node metastasis was seen in 35.8%. In the cases with positive abdominal lymph node, 40.9% of the patients had cervical node metastasis. The most frequent site of the positive node in the neck is the area along the right recurrent laryngeal nerve. On the stand point of removal of metastatic lymph node, neck dissection should be required. Three-field dissection yielded better survival rate than two-field dissection but statistical significance was not obtained. When the patients have cervical lymph node metastasis, they have greater possibility of developing blood borne metastasis. However, this observation does not deny the validity of the three-field dissection. Because this dissection may help reducing nodal spread and nodal recurrence. We have to wait for accumulation of the patients to analyze the definite extent of node dissection for T2 or T3 stage of carcinoma of the lower third of the esophagus with positive abdominal lymph node.

From 1946 to 1976, we examined 1,329 patients who had undergone radical resection for upper and mid-thoracic cancer. Seven patients had a postoperative survival of more than twenty years, 58 more than ten and 137 more than five. Histological and pathological tests were performed: it was thus possible, particularly in patients with a survival of more than ten years, to grade the malignancy according to the classification for histologic malignancy proposed by us for several years (cellular atypism, structural atypism and infiltration). These pathological alterations were closely linked with the prognosis and survival time.

From 1946 to 1976, we studied 1,329 cases of radical resection of upper and mid-thoracic esophageal cancer, a cancer whose prognosis is especially poor. Of these, 7 patients lived longer than 20 years, and 58 longer than 10 years. There were 137 patients who lived for more than 5 years. We particularly examined the ones who lived longer than 10 years, and from the findings of histological and pathological specimens we judged the malignancy grade according to the classification of histological malignancy which we had proposed earlier (cellular atypism, structural atypism, and infiltration). Malignancy grade was demonstrated to be closely associated with the prognosis and survival time.