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We developed l-[3-18F]-α-methyltyrosine (18F-FAMT) as an amino acid tracer for positron emission tomography (PET) imaging. In esophageal cancer, the specificity of 18F-FAMT PET was significantly higher than that of fluoro-2-deoxy-d-glucose (18F-FDG) PET and computed tomography (CT) in the evaluation of individual lymph node groups. Definitive chemoradiotherapy (CRT) has been considered a potentially curative treatment for locoregional esophageal cancer and may achieve the same survival benefits as surgical resection. Clinical evaluation of complete response (CR) is important using several modalities. We evaluated 6 patients who had been diagnosed with clinical CR by FAMT-PET following definitive CRT for esophageal squamous cell carcinoma between June 2008 and July 2012. Treatment evaluation of 18F-FAMT was performed following CRT and approximately 1 month later. In primary tumors, 66.7% of patients (4/6) showed FDG uptake following CRT, whereas that of FAMT was 33.3% (2/6). In lymph node metastases, 50% of patients (3/6) showed FDG uptake following CRT, whereas that of FAMT was 0% (0/6). In the present study, FAMT-PET following CRT was a useful modality to predict clinical CR in esophageal cancer. There is a limit to judging clinical CR by CT or FDG-PET following CRT, because radiation-related esophagitis and reactive mediastinal lymphadenopathy by FDG and wall thickness by CT still remain 1 month following CRT. FAMT-PET is the most useful modality at the present time.

Background: Neoadjuvant chemoradiotherapy (CRT) is frequently performed for esophageal squamous cell carcinoma. In this study, we retrospectively assessed the standardized uptake value (SUV) of FDG-PET against decreased rates of SUV to assess the response of advanced esophageal squamous cell carcinoma patients to neoadjuvant CRT, and the correlation of this response with histopathological findings. Patients and Methods: Thirty-three patients receiving CRT followed by surgery were analyzed. Results: Using the decreased rate of maximum SUV, the sensitivity and specificity in distinguishing complete responders (CR) from non-CR patients was 63% and 44%. Using the maximum SUV before surgery, the sensitivity and specificity for distinguishing pathological CR from non-CR was 88% and 56%. Conclusions: To identify complete responders of CRT for esophageal cancer, absolute maximum SUV value is a better predictor than decreased rate of the maximum SUV.

Heat shock protein 70 is a molecular chaperone important in host responses to stress, including infection, injury, oxidative damage, hypoxia, and thermal stress. This study analyzed the correlation between preoperative serum concentrations of anti-HPS70 antibody and postoperative morbidity in patients with esophageal cancer. Serum samples were obtained preoperatively from 50 esophageal carcinoma patients (46 men and 4 women) who underwent potentially curative surgery without preoperative therapy. Serum anti-HSP70 antibody concentrations were measured by enzyme-linked immunosorbent assays. The mean concentration of anti-HSP70 antibody was 187.0 μg/mL. When patients were dichotomized relative to this cutoff, we observed no significant relationships between perioperative inflammatory markers (maximum body temperature, white blood cell count and C-reactive protein concentration) and anti-HSP70 antibody concentration. The incidence of postoperative complications was significantly lower in patients with anti-HSP ≥ 187.0 μg/mL than

This phase I/II study was aimed to determine the recommended dose (RD) of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for patients with esophageal cancer and to evaluate the efficacy and safety of this protocol.Fourteen patients with esophageal cancer enrolled in this dose escalation study to determine the RD for a phase III trial. Efficacy and toxicity in DCF-RT of RD were evaluated in 37 patients with esophageal cancer.The RD for DCF-RT for esophageal cancer in the present study was 50 mg/m(2) docetaxel plus 60 mg/m(2) cisplatin on day 1 and day 29 plus 600 mg/m(2) 5-FU on days 1-4 and days 29-32 and concurrent radiation of 60 Gy/30 fractions/6 weeks. The main toxicities were myelotoxicity and radiation esophagitis. In this phase I/II study, we could have safety and feasibility by RD, because there was low mortality and most toxicities were manageable level. The complete response (CR) rate and response rate were 54.1 and 83.8 %, respectively, in the phase II study. In patients with a classification of clinical T4, the CR rate and response rate were 47.6 and 85.7 %, respectively. The 2-year overall survival rate, 2-year progression-free survival rate, and median survival time (MST) were 52.9, 50.0 %, and 24.7 months, respectively. In patients with clinical T4 classification, the 2-year overall survival rate, 2-year progression-free survival rate, and MST were 43.5, 44.9 %, and 21.6 months respectively.DCF-RT keeps safety and feasibility by management of myelotoxicity adequately in RD. This protocol might produce a high CR rate and favorable prognosis compared with standard chemoradiotherapy for advanced esophageal cancer.

Esophageal carcinosarcoma (ECS) is a rare malignant neoplasm associated with a poor patient prognosis. It is characterized by the presence of both malignant epithelial and mesenchymal components. Molecular-targeted therapy of several receptor tyrosine kinases (RTKs) has been reported to be effective in the treatment of various malignant tumors, including carcinosarcoma of several organs. This study aimed to assess the therapeutic potential of targeting RTKs in ECS. Overexpression of RTKs was assessed in 21 ECS cases by immunohistochemistry (IHC). Positively stained cases were further examined for RTK gene mutations and amplifications by direct sequencing analysis and fluorescence in situ hybridization. In epithelial components, KIT, platelet-derived growth factor receptor (PDGFR)A, PDGFRB, MET, epidermal growth factor receptor (EGFR) and HER-2 were overexpressed in 1 (4.8%), 1 (4.8%), 0 (0%), 11 (52.4%), 13 (61.9%) and 2 (9.5%) cases, respectively. In the mesenchymal components the corresponding numbers of cases were 2 (9.5%), 2 (9.5%), 0 (0%), 12 (57.1%), 11 (52.4%) and 0 (0%). No mutations in the c-kit, PDGFRA and c-met genes were found. Among 19 EGFR-positive tumors, 2 had EGFR missense mutations (T790A, exon 20) only in the mesenchymal component. Gene amplification or high polysomy of c-kit, PDGFRA, c-met and EGFR was observed in 1 (33.3%), 0 (0%), 3 (18.8%) and 10 (52.6%) cases, respectively. In conclusion, various RTKs, particularly MET and EGFR were overexpressed in ECSs suggesting that molecular-targeted therapies directed to MET, EGFR or other RTKs may be effective in inhibiting the growth or progression of the epithelial and/or mesenchymal component of ECS.

A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m2 DOC plus 70 mg/m2 CDDP on day 1 plus 700 mg/m2 5-FU on days 1–5 at 4-week intervals. This regimen was tolerable and highly active. A phase II study has been started.

Barrett's esophagus (BE) is the premalignant lesion from which esophageal adenocarcinoma near the esophagogastric junction arises. The management of BE and the treatment of Barrett's esophageal adenocarcinoma (BEA) are important clinical issues in Europe and the United States. As the Helicobacter pylori infection rate in Japan is decreasing in the younger population, the incidence of BE and adenocarcinoma arising from BE may start increasing. Thus, we review the current status of BEA and its management. Magnifying endoscopy with narrow-band imaging is important for diagnosing dysplasia arising from BE. In Japan, adenocarcinoma arising from BE is managed the same way as squamous cell carcinoma in the same location. Strategies to prevent BEA may include medication such as non-steroidal anti-inflammatory drugs and proton pump inhibitors, and anti-reflux surgery. Understanding the pathophysiology of BE will help to reduce the incidence of BEA.

The association of microRNAs (miRs) with cancer progression has been established in many cancers including esophageal squamous cell carcinoma (ESCC). A public microarray database showed that the expression of miR‐150 was lower in ESCC than in normal esophageal mucosa. Here, we focused on ZEB1, epithelial‐mesenchymal‐transition (EMT)‐inducer, as a target gene of miR‐150 based on in silico predictions. The purpose of this study was to clarify the clinicopathological significance of miR‐150 in ESCC, and to investigate miR‐150′s EMT‐regulatory ability. Quantitative RT‐PCR was used to evaluate miR‐150 expression in 108 curative resected ESCC samples to determine the clinicopathological significance. Moreover, we examined the in vitro and in vivo function of miR‐150 via degradation of ZEB1. MiR‐150 expression was significantly lower in cancer tissues compared to adjacent non‐cancerous tissues (P < 0.001). Low expression of miR‐150 in ESCC contributed to malignant potential, such as tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, clinical staging, and poor prognosis (P < 0.05). In vitro assays showed that EMT‐inducer‐ZEB1 is a new direct target of miR‐150. Moreover, miR‐150 induced MET‐like changes in TE‐8 cells through ZEB1 degradation (e.g., E‐cadherin expression, vimentin repression, epithelial morphology, and suppression of migration ability), and significantly inhibited tumorigenicity and tumor growth in a mouse xenograft model. Analysis of the regulation of ZEB1 by miR‐150 could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in ESCC. (Cancer Sci 2013; 104: 48–54)

Extramammary Paget's disease (EPD) is rare. We report a case of double anal canal cancers in a patient with a long history of perianal Paget's disease. The patient, a 68-year-old Japanese woman, refused surgery initially and was treated with electron beam therapy, which achieved remission. However, 6 years later, Paget's disease was found to be progressing again and double anal canal tumors were also detected in the proctos and external skin area. We performed abdominoperineal resection (Miles' operation) and lymph node dissection for the Paget's disease with double anal canal tumors. Immunohistochemical staining revealed cytokeratin (CK)-20 expression in the adenocarcinomas and Paget's disease lesion, but not CK-7 or gross cystic disease fluid protein-15 expression. The lesion was joined to the carcinoma by a stalk. The immunohistochemistry results suggested secondary EPD, although it was originally considered to be Paget's carcinoma (primary EPD) based on the clinical history.

Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC. We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC. LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1–3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases. LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is a suppressor of TNF-α mediated apoptosis, and its expression is induced by NF-κB activation. TNFAIP8 expression is significantly increased in various cancer cell lines. A correlation between TNFAIP8 overexpression, cancer progression, and poor prognosis has been described in many reports of human solid cancers. To clarify the functional and clinical significance of the cancer progression-related gene, TNFAIP8, in esophageal squamous cell carcinoma (ESCC), we used immunohistochemistry to demonstrate TNFAIP8 expression in ESCC. Next, TNFAIP8 expression was depleted by using siRNA to examine the function of TNFAIP8 in the proliferation and apoptosis induction of ESCC cell lines. We detected correlations between TNFAIP8 expression and TNM stage (P

Cisplatin is a key chemotherapeutic agent for the treatment of esophageal cancer. We examined the intracellular localization of cisplatin in esophageal cancer cell lines and determined their sensitivity to cisplatin using in-air micro-PIXE (particle induced X-ray emission). Two human esophageal squamous cell carcinoma (ESCC) cell lines, TE-2 and TE-13, were examined for their response to cisplatin using MTT assay, flow cytometry, and DNA fragmentation assays. Real-time reverse transcription-polymerase chain reaction was also used to evaluate the mRNA expression of multidrug resistance protein 2 (MRP2) in both cell lines. Platinum localizations of intracellular and intranuclear were measured using in-air micro-PIXE. TE-2 cells were more sensitive to cisplatin than TE-13 cells (IC(50): 37.5 mum and 56.3 mum, respectively). Flow cytometry analysis confirmed that more TE-2 than TE-13 cells were in the sub-G1 phase. DNA fragmentation assay was analyzed to confirm the MTT assay and flow cytometry results. The expression of MRP2 mRNA in TE-13 cells was stronger than in TE-2 cells. In-air micro-PIXE showed that TE-2 cells had higher intracellular cisplatin concentrations than TE-13 cells and the ratio of intranuclear to intracellular cisplatin in individual cells was not significantly different. We observed the intracellular and intranuclear localization of cisplatin using in-air micro-PIXE. The results of this study suggest that in-air micro-PIXE could be a useful quantitative method for evaluating the cisplatin sensitivity of individual cells. Finally, we speculate that MRP2 in the cell membrane may play an important role in regulating the cisplatin sensitivity of ESCC cells.

Esophageal cancer is one of the most difficult malignancies to cure, and identification of novel prognostic markers for patients with this disease is important. CD24 is a small highly glycosylated mucin-like protein. Several studies have shown that higher CD24 expression is significantly associated with shorter patient survival in various malignant tumors. However, the expression of CD24 and its clinicopathological significance in esophageal cancer remain largely unknown. Immunohistochemical analyses of CD24 and Ki-67 overexpression in 151 cases of esophageal squamous cell carcinoma were performed to examine the relationships of CD24 expression with clinicopathological parameters and patient survival. Five cell lines derived from esophageal cancer were subjected to Western blot analyses to evaluate CD24 expression. Immunohistochemically, CD24 expression was judged to be positive in 61 (40.4%) cases. CD24 expression was associated with lymph node metastasis (p = 0.005), pathologic stage (p = 0.018), number of nodal metastases (p = 0.003), lymphatic invasion (p = 0.002), venous invasion (p < 0.001), and Ki-67 labeling index (p < 0.001). The Pearson’s correlation coefficient between the CD24 expression score and the Ki-67 labeling index was 0.404 (p < 0.001). CD24 expression was associated with disease-free survival (p < 0.001). A Cox multivariate regression analysis revealed that CD24 expression was an independent prognostic factor (p = 0.033). On Western blot analysis, CD24 was detected in all five cell lines. We conclude that overexpression of CD24, which was correlated with Ki-67 expression, is a novel independent prognostic marker for identifying patients with poor prognosis after curative resection of esophageal squamous cell carcinoma.

Diaphragmatic hernia complicating pregnancy is rare and is associated with high morbidity and mortality, particularly if surgical intervention is delayed. We report a case of diaphragmatic hernia in a pregnant 25-year-old woman. The patient was referred to our hospital in respiratory distress in the 28th week of her pregnancy. Chest radiograph and computed tomography showed air-filled bowel loops in the left side of the chest, with a marked mediastinal shift. Immediately after an emergency caesarean section, the herniated abdominal viscera were reduced through the opening in the diaphragm. We resected the ischemic segment of ileum and repaired the diaphragmatic defect with interrupted sutures and a Gore-Tex sheet. She had an uneventful postoperative course and her baby boy also recovered well. We report this case to alert surgeons to the possibility of this rare surgical emergency during pregnancy.

The optimal treatment for locally advanced esophageal carcinoma has not yet been determined. We report results of neoadjuvant hyperthermo-chemoradiotherapy (HCRT) using weekly low-dose docetaxel followed by surgery in patients with advanced esophageal squamous cell carcinoma.Twenty-four patients were enrolled. 7 patients were considered to have inoperable tumors or rejected surgery after HCRT, and the remaining 17 patients had an esophagectomy. Clinical responses, HCRT toxicity and survival after surgery were evaluated.In the 24 patients, the response rate was 41.7%. The pathological complete response (pCR) rate was 17.6% in the 17 patients. HCRT toxicity grade 2 occurred in six patients (25.0%: esophagitis, 4; leukopenia, 6; neutropenia, 4) and grade 3 (pneumonia) in 3 patients (12.5%). The 3- and 5-year survival rates were 56.3% and 50.0%, respectively. When the patients were divided into a pCR group and a pathological partial response (pPR) group, the 3-year survival rates were 66.7% and 42.9% and the 5-year survival rates were 66.7% and 42.9%, respectively (log-rank P = .5842).Esophagectomy after docetaxel HCRT may have potential for prolonging survival in patients with locally advanced esophageal cancer. A larger randomized, controlled study will be required to confirm the benefit of esophagectomy after HCRT.

Esophageal cancer is one of the most difficult malignancies to cure. The prognosis remains unsatisfactory despite significant advances in surgical techniques and perioperative management. The optimal treatment strategy for localized esophageal cancer has not yet been established. Surgical resection remains the mainstay of treatment for esophageal cancer, and curative resection is the most important surgery. Extended esophagectomy with three-field lymphadenectomy provides the highest quality of tumor clearance and prolongation of patient survival. There has been intense effort in developing novel strategies to treat patients with resectable esophageal cancer. Various combined-modality approaches have been attempted to improve treatment outcomes. Definitive chemoradiotherapy has an impact on long-term survival in patients with resectable esophageal cancer. Accordingly, there are three main combined-modality approaches: esophagectomy with adjuvant chemotherapy or chemoradiotherapy; primary definitive chemoradiotherapy with or without salvage esophagectomy, and preoperative chemoradiotherapy followed by planned esophagectomy. Recently, owing to the remarkable advances in optical technology, minimally invasive esophagectomy using endoscopic instruments has been introduced into esophageal cancer surgery. This article reviews recent changes in the treatment of esophageal cancer surgery, and considers the role of esophagectomy.

This report describes an exceedingly rare case of a benign cartilage-containing breast tumor that developed in the right breast of a 52-year-old woman. She found the mass on self examination. Physical examination revealed a 1.5 x 1.4 cm, firm, smooth and mobile lump in the lower medial quadrant close to the nipple of the right breast. Mammography revealed a slightly indistinct margined, oval-shaped, and high density nodule without microcalcifications. On ultrasonography, the lesion was a hypoechoic, oval-shaped mass with an echogenic spot. The border was slightly rough. Fine needle aspiration cytology revealed some giant cells and necrotic tissue. Excisional biopsy was then performed. Histopathologically, the lesion consisted of islands of mature hyaline cartilage with intervening strands of fibrous stroma. Mammary lobules and ducts were lacking within the mass. Fat and muscular components were not present. Therefore chondromatous tumor of the breast was diagnosed.

Received August 3, 2011; Revised September 7, 2011; Accepted September 12, 2011. From the Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan (Tanaka, Miyazaki, Ozawa, Suzuki, Yokobori, Inose, Sohda, Asao, Kuwano) and Department of Surgical Oncology, Dokkyo Medical University, Mibu-machi, Japan (Kato). Correspondence address: Naritaka Tanaka, MD, PhD, Department of General Surgical Science, Gunma University, Graduate School of Medicine, 3-39-22, Figure 1. (A) Silk suture is threaded through the frontal holes of the (C) Schema of A. (D) Schema of B.

We performed a prospective, multi-institutional, phase-II, clinical trial of a docetaxel, nedaplatin, and 5-fluorouracil (DNF) regimen in patients with unresectable esophageal cancer. Our goal was to determine the efficacy and feasibility of this DNF protocol.Thirty-four patients with unresectable esophageal cancer were enrolled and received DNF therapy. The DNF regimen was repeated every 4 weeks for up to 8 weeks, based on the following recommended doses: docetaxel, 60 mg/m(2) (day 1); nedaplatin, 70 mg/m(2) (day 1); and 5-fluorouracil, 700 mg/m(2) (days 1-5). The primary endpoint was the response rate. The secondary endpoints were overall survival and chemotherapy toxicities.The complete response rate and response rate were 5.9 and 47.1 %, respectively. The 2-year overall survival rate and progression-free survival rate were 44.3 and 27.3 %, respectively. The median survival time was 594 days. The median progression-free time was 277 days. No treatment-related deaths occurred. Thirty patients (30/34) with grade 3, 4 neutropenia improved relatively quickly with administration of granulocyte colony-stimulating factor.DNF combination chemotherapy is a useful regimen with relatively minor adverse events and may serve as an effective protocol in patients with unresectable esophageal cancer.

L-[3-(18)F]-α-Methyltyrosine ((18)F-FAMT) has high specificity for malignant tumors on positron emission tomography (PET), and its role and potential usefulness has been previously investigated in operable esophageal carcinoma. We aimed to assess the ability of (18)F-FAMT PET to predict the response of esophageal cancer to definitive chemoradiotherapy.We retrospectively reviewed 40 patients with esophageal cancer imaged with (18)F-FAMT PET. The relationship between (18)F-FAMT PET uptake before chemoradiotherapy and clinical outcomes was assessed.The primary tumor was visualized in 95% patients. (18)F-FAMT uptake was significantly positively correlated with lymph node metastasis. The low-(18)F-FAMT accumulation group had significantly higher complete response (CR) rates than did the high-accumulation group. The addition of a lymph node metastasis category with low (18)F-FAMT uptake provides a more precise predictor of CR.(18)F-FAMT uptake prior to treatment is a good predictor of CR rate after CRT for esophageal cancer.

Squamous papilloma is an extremely rare benign tumor of the esophagus. We report a case in a 63-year-old woman who had no symptoms or any detectable human papillomavirus (HPV) infection. Endoscopy showed that this squamous papilloma of the esophagus was unusual in form, being marginally elevated with a slightly irregular mucosal surface, and stainable with iodine. Endoscopic mucosal resection was performed for both diagnosis and treatment. A commercial HPV detection test kit revealed no sign of any HPV infection.

The objective of the present study was to evaluate the significance of pre-treatment screening for patients with esophageal cancer.A retrospective evaluation of the clinical significance of total colonoscopy in 136 patients with primary esophageal cancer was performed.Twenty-three patients (16.9%) had diverticula, and five (3.7%) had colon cancer. Benign polyps were present in 57 patients (41.9%); 37 of these patients underwent endoscopic treatment, one underwent surgery (esophagectomy). Twenty-seven out of 32 patients (84.4%) who underwent histopathological studies had tubular adenoma. Significant associations were found between presence of colorectal lesions and body weight, body-mass index (p0.001), Brinkman index (p0.001), and the Sake index (p0.05).Screening for colorectal lesions using total colonoscopy is important in patients with esophageal cancer, especially for those with a high body-mass index, and those who smoke or drink heavily.

We reviewed the indications for re-thoracotomy after esophagectomy for esophageal cancer. Hemothorax, chylothorax, tracheobronchial injury (fistula), pneumothorax, and pyothorax were the main causes of re-thoracotomy. Indications for emergency thoracotomy were as follows. 1)Hemothorax:bleeding through the chest drain continuing at100 ml/hour for ≥5 hour, or in cases when normal blood pressure cannot be maintained without blood transfusion. 2)Chylothorax:in cases with ≥1.5 l/day of chyle drainage for5 days under conservative treatment. Healing is not seen for 14 days after conservative treatment. Nutritional status of the patient has worsened. 3)Tracheobronchial injury:at 1st respiration state should be understood. After we maintain the patient's airway, fistula is treated by closure and plombage with omentum or muscle flap. Appropriate diagnosis and timing are important for re-thoracotomy for complications after esophagectomy.

Nonspecific esophageal motility disorder (NEMD) is a vague category that includes patients with poorly defined contraction abnormalities observed during esophageal manometry. This study investigated the therapeutic effects of the video-assisted thoracoscopic surgery (VATS) approach using long myotomy and fundopexy for NEMD.The VATS approach using myotomy and fundopexy was performed for 4 patients of NEMD between 2005 and 2008. A total of 4 patients with NEMD that underwent treatment at our institution were analyzed retrospectively.The patients included 2 males and 2 females with a median age of 48 years (range 21-74 years). The median duration of NEMD symptoms was 58 months (range 4-108 months). Dysphagia was a primary symptom in all patients. Chest pain was a primary symptom in 3 of 4 patients (75 %). Treatment with medication was attempted before the operation. The median operative time was 344.5 min (range 210-476 min). The median time before starting oral feeding was 2.5 days (range 2-22 days). All patients achieved a significant improvement of their previous condition.The VATS approach using myotomy and fundopexy for NEMD is a good treatment in cases resistant to medication and balloon dilation.

CD47 inhibits phagocytosis and its overexpression is correlated with poor prognosis in patients with several types of cancer. It has also been reported that CD47 expression in multiple sclerosis is regulated by microRNAs. However, the regulatory mechanism of CD47 in cancer tissues has not been yet clarified. Re-analysis of a public microarray database revealed that miR-133a is downregulated in esophageal squamous cell carcinoma (ESCC). Moreover, in silico algorithms predicted that miR-133a is a regulator of CD47. The purpose of this study was to clarify the clinical significance of CD47 and its regulatory mechanism by miR-133a in ESCC. Quantitative real-time RT-PCR was used to evaluate CD47 and miR-133a expression in 102 cases of curative resected ESCC and adjacent non-cancerous tissue. The regulation of CD47 by miR-133a was examined with precursor miR-133a-transfected cells. A mouse xenograft model was used to investigate the ability of miR-133a to suppress tumor progression. High expression levels of CD47 were associated with lymph node metastasis (P=0.049). Multivariate analysis showed that CD47 expression was an independent prognostic factor (P=0.045). miR-133a expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (P

Heat shock proteins (HSPs) are well known as tumor rejection antigens, most notable of which is HSP70. HSP110 is classified as a member of the HSP70/DnaK superfamily. The objective of this study was to clarify the clinicopathological and prognostic significance of Heat Shock Protein 110 expression and T lymphocyte infiltration in esophageal cancer.Immunohistochemical staining of HSP110, CD4 and CD8 were performed on surgical specimens obtained from 124 patients with esophageal cancer.The expression of HSP110 correlated inversely with depth of invasion (p0.0001), lymph node metastasis (p=0.0163), pathological stage (p0.0001), lymphatic invasion (p=0.0104), blood vessel invasion (p=0.0027), infiltrative growth pattern (p=0.0368) and correlated positively with CD4+ T lymphocyte infiltration (p=0.0018). Reduction of HSP110 expression was significantly correlated with poor prognosis (p=0.0010).The present findings suggest that HSP110 expression and T lymphocyte infiltration is a significant prognostic factor for esophageal cancer.

Esophageal motility disorders are classified primary and secondary, and primary esophageal motility disorders are classified esophageal achalasia and other diseases by manometry. An esophageal emptying disorder associated with insufficient relaxation of the lower esophageal sphincter (LES) and elimination of peristaltic waves on the esophageal body is the major abnormality of achalasia. Esophagogram, endoscopy, and manometry are used for diagnosis. As pharmacological therapy, administration of a calcium channel blocker or nitrate is useful. The pharmacological therapy is not recommended as long-term basic therapy but as a temporary treatment. At 1st, the balloon dilation method is chosen in treatment of achalasia Surgical treatment is indicated in the following cases: (1) Patients uneffected by balloon dilation, (2) Flask type with grade II to III dilation, and sigmoid type, (3) the gradual progression to the pathophysiological stage, (4) young patients, (5) complicated with esophageal cancer. Laparoscopic Heller-Dor procedure is the most popular surgical procedure, recently. It is somewhat difficult to perform surgical treatment for this functional disease. We should select the most suitable individualized treatment with efficient comprehension of the pathophysiological situation.

Background Ghrelin is a peptide hormone predominantly produced by endocrine cells in the oxyntic mucosa of the stomach and is an endogenous ligand for the growth hormone secretagogue receptor. Ghrelin plays an important role in regulating appetite, food intake, and energy metabolism. We investigated the correlation between clinicopathologic factors and plasma ghrelin concentration before and after esophagectomy with gastric tube reconstruction for esophageal cancer treatment. Methods The study group comprised 25 patients (22 men, three women, age range 46–78 y) with esophageal cancer who underwent esophagectomy with gastric tube reconstruction between 1999 and 2007. Blood samples were collected before and three times after the operation. Plasma concentrations of ghrelin were determined using a sandwich-type enzyme immunoassay kit. Results Plasma ghrelin concentrations were significantly decreased to 38.7% of the preoperative concentration at postoperative d 7. Plasma ghrelin concentrations recovered slightly over 6–24 mo postoperatively. After 36 mo or longer, ghrelin concentrations had returned to preoperative levels. There was no relationship between ghrelin concentrations and gender, location of tumor, tumor stage, operative procedure, and reconstruction route at each time point. There was a significant relationship between the decrease in body mass index and decrease in plasma ghrelin in patients at 6–24 mo after esophagectomy ( P Conclusions Plasma ghrelin concentrations decrease on a temporary basis after esophagectomy with gastric tube reconstruction and are associated with body weight loss after surgery.

A 74-year-old woman was admitted to Gunma University Hospital because of dysphagia symptoms. A gastrointestinal contrast study demonstrated a large esophageal hiatal sliding hernia affecting the passage of barium at the lower end of the esophagus. Manometric studies showed hypotensive pressure in the lower esophageal sphincter (LES) and relaxation failure of the LES during swallowing. We diagnosed a combination of sliding hiatal hernia with nonspecific esophageal motility disorder (NEMD). Thoracoscopically assisted Heller myotomy and Dor fundoplication by abdominal open surgery were then performed. The patient is currently well and is free from dysphagia symptoms. Treatment with combination thoracoscopic and abdominal open surgery was effective. We report here the first case of combined hiatal hernia with NEMD treated by thoracoscopic and abdominal open surgery.

CD151 is a member of the tetraspanins and has recently been reported as a promoter of the malignant progression of cancer. The purpose of this study was to clarify the clinicopathological outcome and prognostic significance of the immunohistochemical expression of CD151 in esophageal squamous cell carcinoma (ESCC).We evaluated the significance of CD151 expression by immunohistochemistry in 138 surgically resected ESCC and the association of CD151 expression with clinicopathological features.Seventy-five (51.7%) ESCC showed a positive expression of CD151, which indicated a significant association with tumor depth (P = 0.004), lymph node metastasis (P = 0.002), distant metastasis (P = 0.025), and lymphatic invasion (P = 0.046), as well as the Ki-67 labeling index (P = 0.011). The 5-year survival rate of ESCC patients with CD151-positive expression was significantly lower than with CD151-negative expression (positive, 43.1%; negative, 63.8%; P = 0.003). Multivariate analysis showed that positive CD151 expression was not an independent factor for poor survival (P = 0.096).CD151 expression is associated with tumor proliferation and invasiveness in ESCC.

Karyopherin-alpha 2 (KPNA2) is a member of the importin alpha family and has recently been reported to play an important role in tumorigenesis and tumor progression. The aim of the current study was to elucidate the clinicopathological significance of immunohistochemical expression of KPNA2 in esophageal squamous cell carcinoma (ESCC).KPNA2 expression was investigated by immunohistochemistry in 116 surgically resected ESCC, and the association of KPNA2 expression with clinicopathologic features was also examined.Sixty (51.7%) ESCCs demonstrated positive expression of KPNA2. Positive expression of KPNA2 showed a significant association with poor differentiation (p=0.015), tumor depth (p=0.001), lymphatic invasion (p0.001), venous invasion (p0.001), and tumor stage (p=0.008). Positive expression of KPNA2 was also significantly associated with Ki-67 labeling index (p=0.039). Univariate analysis revealed that the prognosis of the ESCC patients whose tumors demonstrated positive expression of KPNA2 was significantly poorer than that of those that did not (p=0.009). Multivariate analysis revealed that only tumor depth and the presence of lymph node metastasis, which are strong prognostic factors in ESCC, were independently associated with poor prognosis in this study.KPNA2 expression is associated with poor differentiation, tumor invasiveness, and tumor proliferation in ESCC.

The role and potential usefulness of positron emission tomography (PET) scanning in certain tumors has been widely investigated in recent years. (18)F-FAMT (L-[3-(18)F]-α-methyltyrosine) is an amino acid tracer for PET. This study investigated whether PET/CT with (18)F-FAMT provides additional information for preoperative diagnostic workup of esophageal squamous cell carcinoma compared with that obtained by (18)F-FDG (fluorodeoxyglucose) PET or CT.PET/CT studies with (18)F-FAMT and (18)F-FDG were performed as a part of the preoperative workup in 21 patients with histologically confirmed esophageal squamous cell carcinoma.For the detection of primary esophageal cancer, (18)F-FAMT-PET exhibited a sensitivity of 76.2%, whereas the sensitivity for (18)F-FDG-PET was 90.5% (P = 0.214). (18)F-FAMT uptake in primary tumors showed significant correlation with depth of invasion (P = 0.005), lymph node metastasis (P = 0.045), stage (P = 0.031), and lymphatic invasion (P = 0.029). In the evaluation of individual lymph node groups, (18)F-FAMT-PET exhibited 18.2% sensitivity, 100% specificity, 71.9% accuracy, 100% positive predictive value, and 70.0% negative predictive value, compared with 24.2%, 93.7%, 69.8%, 66.6%, and 70.2%, respectively, for (18)F FDG-PET. CT exhibited 39.4% sensitivity, 85.7% specificity, 69.8% accuracy, 59.1% positive predictive value, and 73.0% negative predictive value. The specificity of (18)F-FAMT-PET is significantly higher than that of (18)F-FDG-PET (P = 0.042) and CT (P = 0.002). (18)F-FAMT-PET did not have any false-positive findings compared to those with (18)F-FDG-PET.Our findings suggest that the addition of (18)F-FAMT-PET to (18)F-FDG-PET and CT would permit more precise staging of esophageal cancer.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms affecting the gastrointestinal tract. Esophageal GISTs are very rare, but recognition of esophageal GISTs has been increasing recently. We report a patient with an esophageal GIST that showed increased uptake on 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). In this case, preoperative diagnosis was assumed to be esophageal cancer, but postoperative histopathological and immunohistochemical examination showed it to be a malignant GIST. We also found an activating mutation of kit in this patient; the mutation type was an in-frame deletion of a portion of the juxtamembrane domain (exon11). FDG-PET is useful not only for evaluating the bioactivity but also the malignant potential of esophageal GISTs.

Esophageal carcinosarcoma is a very rare neoplasm and its clinicopathological characteristics and the prognostic factors that influence the clinical outcome of the patient remain a matter of controversy.Twenty patients with esophageal carcinosarcoma were referred to our institutions. Tissue blocks were reviewed and sections containing both carcinomatous and sarcomatous components were stained for epithelial and mesenchymal markers and a proliferating cell marker. The prognosis of the esophageal carcinosarcoma patients was compared with 142 cases of esophageal squamous cell carcinoma.In the carcinomatous component, the expression of cytokeratin, epithelial membrane antigen, vimentin, smooth muscle actin, and S100 were detected in 20, 20, 1, 1, and 1 case, respectively, whereas in the sarcomatous component, expression of these were detected in 4, 2, 18, 15, and 3 cases, respectively. The Ki-67 labeling index of carcinomatous and sarcomatous components was 35.5% and 41.8%, respectively. The 5-year survival rate was not statistically different between squamous cell carcinoma and carcinosarcoma (p=0.219). However, for T1 cases only, carcinosarcoma patients had statistically poorer prognosis than did squamous cell carcinoma patients (p=0.008).The sarcomatous component shows various histological and immunohistochemical forms. In comparison with squamous cell carcinoma patients, carcinosarcoma patients had poorer prognosis amongst the T1 cases. For the treatment of esophageal carcinosarcoma, it is important to monitor lymph nodes and be watchful for hematogenous metastasis, as in cases of esophageal squamous cell carcinoma.

BACKGROUND: Metabolic tumor activity using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was believed to have a predictive value for patient outcome in malignancies. The objective of the current study was to assess the prognostic effectiveness of the highest standardized uptake value (SUV) in the primary or regional area (peak SUV) and the number of PET-positive lymph nodes in esophageal cancer. METHODS: The authors retrospectively reviewed their experience with 184 consecutive esophageal cancer patients imaged preoperatively using FDG-PET scanning. RESULTS: The median peak SUV was 4.5 (range, 1.4-21.9). The survival curve was analyzed using the median peak SUV as the cutoff value. Comparison of each group and clinicopathologic characteristics revealed significant associations between peak SUV and each of the following factors: tumor status (P < .001), lymph node status (P < .001), metastatic status (P < .05), stage of disease (P < .001), number of PET-positive lymph nodes (P < .001), and the number of histologically positive lymph nodes (P < .001). The 5-year overall survival (OS) rate for patients having FDG uptake with a peak SUV ≥4.5 was 47% and that for patients with a peak SUV

Cell cycle regulators, such as cyclinD1 and p53, play major roles in the tumor response to radiation and chemotherapy in esophageal squamous cell carcinoma (SCC). Pin1-mediated prolyl-isomerization potentiates cell cycle progression and cell proliferation, including the regulation of cyclinD1 and p53. Herein, we investigated the effect of Pin1 in association with cyclinD1 and p53 on the sensitivity of esophageal SCC to chemoradiotherapy (CRT). The expression levels of Pin1, cyclinD1 and p53 were examined immunohistochemically in endoscopic biopsy specimens from 68 advanced esophageal SCC patients before CRT to determine whether their expression levels predicted the clinical effectiveness of CRT in individual cancers. Forty-six of the 68 patients (67.6%) had an effective response to CRT, whereas 22 patients (32.4%) had an ineffective response. There was no significant correlation between clinical responses and expression levels of cyclinD1 or p53. However, the clinical response of the high Pin1 expression group was significantly higher than that of the low expression group (P=0.0200). Moreover, our data indicate that the combined immunohistochemical evaluation of Pin1, cyclinD1 and p53 expression in pretreatment biopsy samples is a useful indicator of sensitivity to CRT in advanced esophageal SCC. Thus, Pin1 may influence cyclinD1 and p53 functions and predict CRT sensitivity.

Lysyl oxidase (LOX), an extracellular matrix-remodeling enzyme, has been reported to regulate tumor metastasis. We investigated the clinical significance of LOX expression in esophageal squamous cell carcinoma (ESCC).We examined LOX expression in ESCC cell lines by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting. We also examined LOX expression by real-time RT-PCR in 39 surgically resected ESCC and by immunohistochemistry in 122 surgically resected ESCC.LOX messenger RNA (mRNA) was expressed at a high level in TTn (originating from an ESCC metastatic lesion); at a moderate level in TE-2 and TE-15; and at a low level in TE-1, TE-8, and TE-13. In Western blotting, all cell lines expressed the catalytically inactive 50-kDa LOX at approximately the same levels, but catalytically active 32-kDa LOX was overexpressed only in TTn. LOX mRNA levels in ESCC tissues were significantly higher than those observed in normal esophageal tissues (P0.001) and had no significant correlation with tumor-node-metastasis (TNM) factors. High LOX protein expression had a significant correlation with presence of lymph node metastasis (P = 0.009) and number of lymph node metastases (P = 0.047). Overall and cancer-specific survival rates of patients with ESCC with high LOX expression were significantly lower than those of patients with ESCC with low LOX expression (P = 0.024 and P = 0.012). Univariate and multivariate analyses revealed that high LOX protein expression was an independent prognostic factor for ESCC.Our findings suggest that LOX can serve as a predictive marker of lymph node metastasis and prognosis in ESCC.

Carbonic anhydrase 9 (CA9) is a protein to be upregulated under exposure to hypoxic conditions. Hypoxic conditions are known to be associated with resistance to chemotherapy and radiotherapy, and with poor cancer prognosis. We examined CA9 expression in surgical specimens from oesophageal squamous cell carcinoma (ESCC) patients (n=127) using immunohistochemistry and real-time RT-PCR. We also examined CA9 expression and cell proliferation in ESCC cell lines (TE-2, TE-8 and TE-15) and an immortalised human oesophageal cell line (CHEK-1) using real-time RT-PCR, Western blotting, ELISA and MTT assay. Immunohistochemistry, high expression of CA9 was found in 63 of the 127 primary tumour specimens and was correlated with poor outcome (P=0.0003) and more aggressive/less favourable clinicopathological parameters (tumour size (P=0.0235), tumour depth (P

The purpose of the present study was to assess the contribution of simultaneous functional/anatomical imaging using integrated 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), compared with PET alone for the evaluation of initial lymph node staging in esophageal cancer. We studied 167 consecutive patients with thoracic esophageal squamous cell carcinoma (SCC) who had radical esophagectomy performed between January 1999 and April 2007. For individual nodal group evaluation, PET/CT showed 46.0% sensitivity (p

Circulating vascular endothelial growth factor-C (VEGF-C) levels were measured in patients with esophageal cancer to assess the value of VEGF-C as a biomarker for predicting tumor recurrence.Preoperative serum samples were acquired from 80 patients and healthy volunteers who served as normal controls. VEGF-C levels were assessed using enzyme-linked immunosorbent assay (ELISA).The preoperative serum VEGF-C level in patients with esophageal cancer was significantly higher than in healthy volunteers. Furthermore, patients with recurrence had significantly higher preoperative serum VEGF-C levels than patients without recurrence, and a high preoperative serum VEGF-C level was found to be an independent risk factor for recurrence, in addition to lymph node metastasis.Preoperative VEGF-C levels may reflect malignancy, such as lymph node metastasis, and predict recurrence in patients with esophageal cancer. Therefore, the preoperative VEGF-C level may be a useful biomarker for choice of multimodality therapy.

After esophagectomy a swallowing abnormality is the predominant symptom for esophageal cancer. The aims of this study were to examine (i) oropharyngeal swallowing by comparing pre- and postoperative period, and (ii) the relationship between oropharyngeal swallowing and the alimentary reconstruction route after esophagectomy.We studied 27 patients in the upright position using videofluoroscopy in the lateral projection. Each patient was studied during 10 mL barium swallows in the pre- and post-operative period.Of the 27 patients studied, alimentary reconstruction with the retrosternal route (RS group) was performed in 8 patients, that with posterior mediastinal route (PM group) in 8 patients, and the intrathoracic (IT group) esophagogastrostomy inside the posterior mediastinum in 11 patients. With regard to the maximal extent of structural movement, the superior and anterior excursion of the hyoid bone was significantly reduced postoperatively among all groups. The maximal extent of the cricopharyngeal opening was significantly reduced postoperatively in the RS group, but not in the IT group. The changes in the peri-operative structural movement were the lowest in the RS group.A new-onset oropharyngeal swallowing abnormality following retrosternal reconstruction after esophagectomy may have appeared because the change in the peri-operative movement was the lowest. The results of the swallowing evaluation using videofluoroscopy suggest that to avoid oropharyngeal swallowing abnormalities the intrathoracic or cervical anastomosis with posterior mediastinal route should be chosen as reconstruction after esophagectomy if possible.

Esophageal cancer is one of the most difficult malignancies to cure. The prognosis remains unsatisfactory despite significant advances in surgical techniques and perioperative management. The optimal treatment strategy for localized esophageal cancer has not yet been established. Surgical resection remains the mainstay of treatment for esophageal cancer, and curative resection is the most important surgery. Extended esophagectomy with three-field lymphadenectomy provides the highest quality of tumor clearance and prolongation of patient survival. There has been intense effort in developing novel strategies to treat patients with resectable esophageal cancer. Various combined-modality approaches have been attempted to improve treatment outcomes. Definitive chemoradiotherapy has an impact on long-term survival in patients with resectable esophageal cancer. Accordingly, there are three main combined-modality approaches: esophagectomy with adjuvant chemotherapy or chemoradiotherapy; primary definitive chemoradiotherapy with or without salvage esophagectomy, and preoperative chemoradiotherapy followed by planned esophagectomy. Recently, owing to the remarkable advances in optical technology, minimally invasive esophagectomy using endoscopic instruments has been introduced into esophageal cancer surgery. This article reviews recent changes in the treatment of esophageal cancer surgery, and considers the role of esophagectomy.

We have been investigating various molecules correlated with the malignancy of esophageal squamous cell carcinoma and, in the present study, we examined the correlation of four of them (KAI1, FAK, EphA2, Ki-67 labeling index) with the prognosis of affected patients. Furthermore, the use of biopsy samples was studied to evaluate whether the grade of tumor malignancy can be determined before treatment in a clinical setting.Tissue specimens that had been surgically removed from 91 patients with thoracic esophageal cancer and 247 biopsy samples were examined. The malignancy index (MI) was defined in terms of the KAI1, FAK and EphA2 scores and the Ki-67 labeling index, and the reliability and utility of the correlation between MI and prognosis was evaluated.The mean 5-year survival rate of patients with MI=0 was 100%, while that of patients with MI=1, 2 and 3 was 70%, 48% and 10%, respectively. Patients with MI=4 all died, with the exception of one who has been observed for 3 years. The rate of concordance between the biopsy samples and surgical specimens was 79.4% for KAI1, 88.2% for FAK and 73.5% for EphA2, and the rates of concordance for 1, 2, 3, 4, 5, 6, 7 and 8 biopsy samples were 66.7%, 64.1%, 74.5%, 90.7%, 91.7%, 83.3%, 100% and 100%, respectively.It may be feasible to evaluate the malignancy of tumor cells and to predict patient outcome by using multiple marker molecules. It is anticipated that such data will accelerate the development of "tailor-made" therapy.

We investigated whether Helicobacter pylori (HP) eradication increases the incidence of reflux esophagitis (RE) in patients with peptic ulcers. From 2001-2005 consecutive out patients with peptic ulcers and HP received eradication and were followed endoscopically. HP was cured in 119 and RE developed in 33 of the 153 patients. RE developed in 24 of the 119 HP-eradicated patients and 9 of the 34 HP-persistent patients. The estimated RE occurrence rate within 1 year was higher in the HP-eradicated patients than in the HP-persistent patients, but it was reversed at 2 years by the Kaplan-Meier analysis. In 76 patients follow up foror = 18 months, hiatal hernia, duodenal ulcer, and eradication failure were significantly associated with the increased RE rate by univariate and multivariate analysis. The follow-up period after HP eradication affected the RE occurrence rate, and eradication failure significantly increased the RE development in patients followed up foror = 18 months.

Background. Intensive care unit (ICU) psychosis is still a relatively frequent complication after esophageal surgery. We investigated the correlation between ICU psychosis and serum melatonin concentration during the period after esophagectomy. Methods. The study group comprised 41 patients who underwent esophagectomy for treatment of esophageal cancer between 1999 and 2001. The cohort included 36 men and 5 women, aged 36 to 78 years. After surgery, blood samples were collected 4 times a day for 4 days. Serum levels of melatonin were determined with a melatonin radioimmunoassay kit. The regularity of the melatonin circadian rhythm pattern, as defined by the frequency of occurrence of the peak level of melatonin secretion, was determined (the pattern was described as irregular at less than 3 times in the measurement period). Results. Of the 41 patients who met the inclusion criteria, 11 (26.8%) had ICU psychosis develop. These patients were older than those patients in whom ICU psychosis did not develop (P =.01). No significant differences were seen in the duration of surgery, volume of blood loss, term in the ICU, term of intubation, tumor location, disturbances of organ function, and postoperative complications between patients in whom ICU psychosis developed, and those patients in whom it did not. Patients with ICU psychosis tended to have abnormally low serum levels of melatonin. Of the 41 patients studied, 9 (22%) had an irregular pattern of melatonin circadian rhythm. A significant correlation was seen between ICU psychosis and an irregular melatonin circadian rhythm (P =.0001). Conclusion. Irregular patterns of melatonin circadian rhythm may be associated with ICU psychosis. Supplementation with melatonin, or acceleration of melatonin secretion, may protect patients from development of ICU psychosis and may promote recovery to a normal mental state. (Surgery 2003;133:662-8.)