Immunochemical Approach for Monitoring of Structural Transition of ApoA-I upon HDL Formation Using Novel Monoclonal Antibodies.

Apolipoprotein A-I (apoA-I) undergoes a large conformational reorganization during remodeling of high-density lipoprotein (HDL) particles. To detect structural transition of apoA-I upon HDL formation, we developed novel monoclonal antibodies (mAbs). Splenocytes from BALB/c mice immunized with a recombinant human apoA-I, with or without conjugation with keyhole limpet hemocyanin, were fused with P3/NS1/1-Ag4-1 myeloma cells. After the HAT-selection and cloning, we established nine hybridoma clones secreting anti-apoA-I mAbs in which four mAbs recognize epitopes on the N-terminal half of apoA-I while the other five mAbs recognize the central region. ELISA and bio-layer interferometry measurements demonstrated that mAbs whose epitopes are within residues 1-43 or 44-65 obviously discriminate discoidal and spherical reconstituted HDL particles despite their great reactivities to lipid-free apoA-I and plasma HDL, suggesting the possibility of these mAbs to detect structural transition of apoA-I on HDL. Importantly, a helix-disrupting mutation of W50R into residues 44-65 restored the immunoreactivity of mAbs whose epitope being within residues 44-65 against reconstituted HDL particles, indicating that these mAbs specifically recognize the epitope region in a random coil state. These results encourage us to develop mAbs targeting epitopes in the N-terminal residues of apoA-I as useful probes for monitoring formation and remodeling of HDL particles.

Enthalpy-driven interactions with sulfated glycosaminoglycans promote cell membrane penetration of arginine peptides.

The first step of cell membrane penetration of arginine peptides is thought to occur via electrostatic interactions between positive charges of arginine residues and negative charges of sulfated glycosaminoglycans (GAGs) on the cell surface. However, the molecular interaction of arginine peptides with GAG still remains unclear. Here, we compared the interactions of several arginine peptides of Tat, R8, and Rev and their analogues with heparin in relation to the cell membrane penetration efficiency. The high-affinity binding of arginine peptides to heparin was shown to be driven by large favorable enthalpy contributions, possibly reflecting multidentate hydrogen bondings of arginine residues with sulfate groups of heparin. Interestingly, the lysine peptides in which all arginine residues are substituted with lysine residues exhibited negligible binding enthalpy despite of their considerable binding to heparin. In CHO-K1 cells, arginine peptides exhibited a great cell-penetrating ability whereas their corresponding lysine peptides did not penetrate into cells. The degree of cell penetration of arginine peptides markedly decreased by the chlorate treatment of cells which prevents the sulfation of GAG chains. Significantly, the cell penetration efficiency of arginine peptides was found to be correlated with the favorable enthalpy of binding to heparin. These results suggest that the enthalpy-driven strong interaction with sulfated GAGs such as heparan sulfate plays a critical role in the efficient cell membrane penetration of arginine peptides.

Effect of Notch expression in glioma stem cells on therapeutic response to chemo-radiotherapy in recurrent glioblastoma.

Glioma stem cells (GSCs) have the capacity to repopulate tumors and mediate resistance to radiotherapy and chemotherapy. The Notch signaling pathway is important in proliferation, stem cell maintenance, cell differentiation, and tumorigenesis in GSCs. In this study, we compared CD133, Notch, and VEGF expressions in histological sections of primary and recurrent glioblastomas after radiotherapy and chemotherapy. In vitro study, the γ-secretase inhibitor inhibited NICD, Hes1 and pVEGFR2 expressions in GSCs. GSCs cultured under endothelial conditions undergo endothelial differentiation. Tumor samples were collected from 27 patients at the time of tumor recurrence. We used immunohistochemical techniques to compare expression of CD133, Notch-1 and VEGF. Expressions of CD133-, Notch-1-, and VEGF-positive glioma cells were higher in recurrent glioblastoma after radiotherapy and chemotherapy. To determine the clinical importance of Notch-1 expression in glioblastoma, we analyzed 15 patients who had received bevacizumab therapy followed by a second surgery at recurrence. OS was significantly longer in cases with Notch-1 negativity (8.8 months) than in those with I Notch-1 positivity (6.8 months). We noted that GSCs have the potential for endothelial differentiation with Notch activity. We believe that Notch-1 is a potential target and/or biomarker for antiangiogenic treatments.

An Intra-Abdominal Pseudocyst around a Ventriculoperitoneal Shunt due to Streptococcus Infection 7 Years after Shunt Surgery.

In 1999, a 50-year-old woman underwent ventriculoperitoneal (VP) shunt surgery for hydrocephalus after subarachnoid hemorrhage. She was hospitalized for fever and recurrent systemic seizures in November 2006. Head computed tomography (CT) showed only old changes. The seizures and fever were controlled by medicinal therapy. However, in December, her consciousness level suddenly decreased, and she showed progressive lower abdominal distension. Head CT showed marked ventriculomegaly, and abdominal CT showed a giant cystic mass at the shunt-tube tip in the lower abdominal cavity. Because thick pus was aspirated from the intra-abdominal mass, we diagnosed the patient with acute obstructive hydrocephalus due to an infected abdominal pseudocyst. Laparotomy and direct cyst drainage were performed, and antibiotic therapy against Streptococcus, the causative pathogen, was administered. The VP shunt tube was replaced. The postoperative course was uneventful, and postoperative CT showed hydrocephalus improvement and no pseudocyst recurrence. Abdominal pseudocysts, which are rare after VP shunt surgeries, usually occur after the subacute postoperative course in younger cerebral hemorrhagic cases. Our case was quite rare because the cyst developed in the chronic phase in an older patient and was caused by streptococcal infection. The cyst components should be examined before cyst drainage when choosing surgical strategies.

Treatment of moyamoya syndrome associated with systemic lupus erythematosus and hypothyroidism in an adult by encephaloduroarteriosynangiosis: a case report.

A 54-year-old woman presented to our hospital with progressive motor weakness of the right arm. She had a medical history of systemic lupus erythematosus (SLE) and hypothyroidism. Magnetic resonance imaging indicated a watershed infarction of the left hemisphere. Cervical echogram indicated severe stenosis of the internal carotid artery (ICA) without wall thickening. Cerebral angiography indicated left ICA occlusion, development of unilateral moyamoya vessels, and leptomeningeal anastomosis. Encephaloduroarteriosynangiosis (EDAS) was performed after cerebral (99) (m)Technetium-ethyl-cysteinate-dimer single-photon emission computed tomography indicated a decreased cerebral blood flow, diminished cerebrovascular perfusion reserve. Motor weakness finally disappeared 6 months after surgery. Moyamoya syndrome is a rare complication of both SLE and hypothyroidism, and the surgical indication remains controversial. By evaluating the decreased cerebral perfusion reserve capacity and the existence of leptomeningeal anastomosis, EDAS could be an efficient method for the treatment of moyamoya syndrome associated with SLE and hypothyroidism.

Posttraumatic cranial cystic fibrous dysplasia.

A 14-year-old was girl admitted to our hospital with a subcutaneous mass of the occipital head. The mass had grown for 6 years, after she had sustained a head injury at the age of 6, and was located directly under a previous wound. Skull X-ray Photograph (xp), computed tomography (CT), and magnetic resonance imaging (MRI) showed a bony defect and cystic changes in the skull corresponding to a subcutaneous mass. Bone scintigraphy revealed partial accumulation. The patient underwent total removal of the skull mass, and the diagnosis from the pathological findings of the cyst wall was fibrous dysplasia (FD). The radiographic findings for cystic cranial FD can be various. Progressive skull disease has been reported to be associated with head trauma, but the relationship between cranial FD and head trauma has not been previously reported. Previous studies have suggested that c-fos gene expression is a key mechanism in injury-induced FD.

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents --special references to bacteria isolated between April 2008 and March 2009].

Bacteria isolated from infections in abdominal surgery during the period from April 2008 to March 2009 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 712 strains including 18 strains of Candida spp. were isolated from 173 (80.5%) of 215 patients with surgical infections. Three hundred and sixty-six strains were isolated from primary infections, and 346 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from postoperative infections aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp., and Staphylococcus spp. in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from postoperative infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa, in this order, and from postoperative infections, P aeruginosa was most predominantly isolated, followed by E. coli, Enterobacter cloacae, and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Streptococcus constellatus and Gemella morbillorum, and from postoperative infections, E. lenta was most predominantly isolated. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis was the highest from primary infections, followed by Bacteroides thetaiotaomicron, Bacteroides ovatus and Bilophila wadsworthia, and from postoperative infections, B. fragilis was most predominantly isolated, followed by B. thetaiotaomicron, B. wadsworthia and B. ovatus, in this order. In this series, we noticed no vancomycin-resistant methicillin-resistant S. aureus, and Enterococcus spp., nor multidrug-resistant P aeruginosa. We should carefully follow up B. wadsworthia which was resistant to various antibiotics, and also Bacteroides spp. which was resistant to many beta-lactam antibiotics.

Quantitative analysis of cisplatin sensitivity of human esophageal squamous cancer cell lines using in-air micro-PIXE.

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.

[Revision of the informed consent form for patients based on investigation of adverse events of mFOLFOX6 regimen].

We retrospectively investigated the frequency and severity of adverse events in 124 patients with colorectal cancer who were treated by mFOLFOX6 regimen from August, 2005 to December, 2006. The incidences of grade 3/4 adverse events were; leucopenia 16%, neutropenia 40%, anemia 11%, thrombocytopenia 7%, febrile neutropenia 7%, nausea 3%, vomiting 2%, anorexia 2%, diarrhea 4%, fatigue 7%, and alopecia 0%. The incidences of all grades and grade 3/4 hypersensitivity reaction were 35% and 4%, and the median number of course when it firstly appeared was 6(range, 1-21). The incidences of all grade and grade 3 peripheral sensory neuropathy were 74% and 6%, and the median number of course when it firstly appeared 11(range, 6-16). The incidences of adverse events in this cohort were similar or lower than those reported in Western countries. Our investigation shows that mFOLFOX6 regimen is tolerable in clinical practice in Japan. The informed consent form was revised based on these results. The incidences of adverse events were renewed to provide useful information and improve self-care ability. The symptoms and the time to appearance of the hypersensitivity reaction and peripheral sensory neuropathy were added. We think it is important to provide the information based on the clinical practice.

Expression of lysyl oxidase is correlated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: 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). METHODS: 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. RESULTS: 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 (P < 0.001) 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. CONCLUSIONS: Our findings suggest that LOX can serve as a predictive marker of lymph node metastasis and prognosis in ESCC.

Correlation between connexin 26 expression and poor prognosis of esophageal squamous cell carcinoma.

BACKGROUND: Failure of gap junction formation affects the development of various types of cancer. We aimed to clarify the clinicopathologic outcome and prognostic significance of connexin (Cx) 26 in human esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemical staining for Cx26 was performed on surgical specimens obtained from 123 patients with ESCC. RESULTS: There was no positive staining for Cx26-specific expression in normal esophageal squamous cells. Primary ESCC with Cx26-positive expression was detected in the cytoplasm of cancer cell nests in 60 cases. Cx26 expression was correlated with N (lymph node metastasis, P = 0.014) and the number of metastatic lymph nodes (P = 0.047). The 5-year survival rates of ESCC patients with Cx26-positive expression were significantly lower than those with Cx26-negative expression (positive, 39.7%; negative, 65.7%; P = 0.007). By multivariate analysis, tumor-node-metastasis (TNM) clinical classification (T, P < 0.001; N, P = 0.002; M, P = 0.046) and Cx26 (P = 0.024) were independent prognosis predictors of ESCC. CONCLUSIONS: These results suggest that abnormal expression of Cx26 participates in the progress of ESCC.

Immunohistochemical analysis of phosphorylated epidermal growth factor receptor might provide a surrogate marker of EGFR mutation.

PURPOSE: Overexpression of EGFR is found in several malignancies including lung cancers. Recently, EGFR mutation has been shown to correlate with responsiveness to tyrosine kinase inhibitors (TKI). Although antibodies against phophorylated EGFR have been used in vitro, phosphorylated EGFR has yet not been examined well in resected non-small cell lung cancers (NSCLCs). EXPERIMENTAL DESIGN: We studied the immunohistochemistry of anti-EGFR and phosphorylated EGFR in 97 resected NSCLCs, examined the relationship with EGFR mutation, and performed quantitative RT-PCR of the EGFR gene in the TaqMan assay. RESULT: EGFR mutation was seen in 27% of 97 NSCLCs and 37% of 70 adenocarcinomas. EGFR was stained in 60% of 97 NSCLCs. Phosphorylation of tyrosine 845 (pY845) and 1068 (pY1068) was positive in 49% and 48%, respectively. The observed correlation with EGFR mutation and pY845 or pY1068 was statistically significant (P=0.0001 for pY845, P<0.0001 for pY1068, chi square test), although phospho-EGFR status was not associated with a particular mutation type. pY1068-positive tumors also correlated with female, light smoker, and adenocarcinoma histology, but not with mRNA expression. Moreover, patients with pY1068-positive tumors showed prolonged survival (P=0.0093, log-rank test). CONCLUSION: It is possible that immunohistochemistry of phosphorylated EGFR can substitute for EGFR mutation analysis. Further investigation is necessary to determine whether phospho-EGFR immunohistochemistry predicts response to TKIs and survival benefit.

The additional value of integrated PET/CT over PET in initial lymph node staging of esophageal cancer.

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<0.05 vs. PET), 99.4% specificity, 95.1% accuracy (p<0.05 vs. PET), 87.0% positive and 95.5% negative predictive values. PET showed 32.9% sensitivity, 98.9% specificity, 93.1% accuracy, 74.7% positive predictive value and 93.9% negative predictive value. Thus, the sensitivity and accuracy of PET/CT were significantly higher than those of PET. Comparisons between CT, PET and PET/CT in detecting lymph node metastasis by each region showed that PET/CT had a higher sensitivity in lower thoracic regions than PET and CT (p<0.05 vs. CT and PET). Lymph node staging (N0 vs. N1) was not significantly different, but staging per lymph nodal group was significantly better with PET/CT. Integrated PET/CT imaging with co-registration of anatomic and functional imaging data is useful in the initial lymph node staging of patients with operable esophageal cancer compared with PET alone.

Diaphragmatic hernia with ischemic bowel obstruction in pregnancy: report of a case.

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.

Esophageal granular cell tumor covered by intramucosal squamous cell carcinoma: report of a case.

We report a case of a granular cell tumor (GCT) covered by squamous cell carcinoma (SCC) in the esophagus. A 69-year-old Japanese man was admitted to our hospital for treatment of superficial esophageal cancer detected by upper gastrointestinal endoscopy. Endoscopic examination revealed a shallow ulcer in the esophagus, 28-32 cm from the incisor teeth. The pathological findings of a biopsy of the lesion were moderately differentiated SCC. Thus, we performed partial esophagectomy with two-field (thoraco-abdominal) lymph node dissection. Microscopic examination of the surgical specimen revealed intraepithelial SCC with minimal invasion, and a GCT, 3 x 1 mm in size, in the submucosa just beneath the SCC. Cytoplasmic granules in the GCT were positive for periodic acid-Schiff. Immunohistochemically, the GCT was strongly positive for S-100 protein. To our knowledge, this is the first published report of a GCT covered by SCC in the esophagus.

Effect of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve to gastrointestinal function: an experimental study in conscious dogs.

OBJECTIVE: To evaluate the effects of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve on gastrointestinal function. SUMMARY BACKGROUND DATA: The operative procedure of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve is now in the spotlight in Japan with the goal of finding a function-preserving surgical technique. However, there has been no analysis of the effect of this type of surgery on gastrointestinal function. In this article, we describe the results of a fundamental experiment on distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve. METHODS: Twenty conscious dogs were divided into 2 groups, each subdivided into 2 groups of 5: a normal intact dog group (NG) divided into 2 groups, with preservation (PNG) and resection (RNG; these dogs were truncally vagotomized including transaction of the celiac branch) of the celiac branch, and a gastrectomy dog group (GG) divided into 2 groups, with preservation (PGG) and resection (RGG) of the celiac branch. The motility of the dogs was recorded using strain gauge force transducers. The effects of the preservation of the celiac branch of the vagus nerve on gastrointestinal motility, gastric emptying, and pancreatic insulin release were evaluated. RESULTS: The motility index of gastrointestinal motility with preservation of the celiac branch was higher than the motility index with resection of the celiac branch in fasted and fed of NG and GG. In gastric emptying, significant differences were found between the PNG and RNG but not between the PGG and RGG. In the fasted state for 80 minutes of the PNG and PGG, the serum insulin concentration reached a peak during the early phase III at 20 minutes in the gastric body and the antrum. CONCLUSIONS: This study has shown that it is effective to preserve the celiac branch of the vagus nerve for gastroduodenal motility, gastric emptying, and pancreatic insulin release after a gastrectomy.

Preoperative serum vascular endothelial growth factor-C (VEGF-C) levels predict recurrence in patients with esophageal cancer.

BACKGROUND: 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. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Clinical applications of 18F-fluorodeoxyglucose positron emission tomography in gastrointestinal stromal tumor of the esophagus.

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.

Prediction of response to definitive chemoradiotherapy in esophageal cancer using positron emission tomography.

BACKGROUND: Positron emission tomography (PET) with 18-F-fluorodeoxyglucose (FDG) has already proven useful in assessing the extension of esophageal carcinomas, detecting tumor recurrence and monitoring responses to therapy. The current study aims to assess the potential role of FDG-PET in predicting the response of esophageal squamous cell carcinoma (SCC) to definitive chemoradiotherapy (CRT). PATIENTS AND METHODS: Twenty-seven patients with thoracic esophageal SCC who received definitive CRT between January 2001 and December 2005 underwent PET before and after CRT. The clinical evaluation of the primary tumor response to treatment was classified as either complete response (CR) or non-CR. RESULTS: All patients had intensive FDG uptake in the primary tumor prior to CRT. The standardized uptake value (SUV) averaged 8.2+/-4.7 before CRT and decreased significantly to 2.8+/-1.8 after CRT (p<0.0001). The SUV before CRT averaged 10.2 in the non-CR group (n=17) and 4.9 in the CR group (n= 10). The SUV after CRT averaged 3.7 in the non-CR group and 1.4 in the CR group. The change in SUV for the CR group was higher than that in the non-CR group (p<0.05). The relationship between clinical features and clinical CR was analyzed using logistic regression analysis which revealed significant correlations between clinical CR and the longitudinal dimension of the tumor (p <0.05), SUV before CRT (p<0.05), SUV after CRT (p<0.01) and tumor classification (p <0.05). If the clinical features before CRT were limited, multivariate analysis revealed that the SUV before CRT was an independent predictor for clinical CR (p<0.05). CONCLUSION: In predicting clinical evaluation of therapy prior to CRT, we suggest that SUV prior to definitive CRT is one of the most reliable predictors of response, along with tumor dimensions and classification.

Surgical treatment for esophageal cancer. Current issues.

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.