Endoscopic endonasal transturbinate approach to the pterygopalatine fossa in the management of juvenile nasopharyngeal angiofibromas.

Pterygopalatine fossa (PPF) is a difficult-to-access anatomic area located behind the posterior wall of the maxillary sinus. Juvenile nasopharyngeal angiofibroma (JNA) often affects this area, and the management of feeding artery to the tumor is important in the surgery. Endoscopic endonasal approach to the PPF without endangering all other nasal structures is useful in the management of JNA. We describe a new approach to the PPF, endoscopic transturbinate approach, which is effective in the management of JNA. Submucous inferior turbinoplasty was performed, and sphenopalatine artery, the feeder to the tumor, was identified at the sphenopalatine foramen. The posterior wall of maxillary sinus was removed. Internal maxillary artery was identified in the PPF and was ligated with a hemoclip. The tumor in the PPF was pushed into the nasal cavity. These procedures were all performed via submucous turbinate tunnel. Then, the tumor was successfully removed in en bloc from the nasal cavity by transnasal approach without ethmoidectomy. This approach improves accessibility and visualization in the PPF and potential to reduce intraoperative bleeding due to ligation of the feeder safely without touching the tumor. Endoscopic transturbinate approach is effective in the management of early stage of JNA.

Proteomics-based identification of autoantibody against heat shock protein 70 as a diagnostic marker in esophageal squamous cell carcinoma.

Detection of novel tumor-related antigens and autoantibodies in cancer patients is expected to facilitate the diagnosis of early-stage malignant tumor and establish effective new immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (TE-2) and related autoantibodies in sera from patients with ESCC using a proteomics-based approach. TE-2 proteins were separated by two-dimensional polyacrylamide gel electrophoresis, followed by Western blot analysis in which sera from patients with ESCC, healthy controls and patients with other cancers were tested for primary antibodies. Positive spots were excised from silver-stained gels and analyzed by matrix-assisted laser disorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Sera from patients with ESCC yielded multiple spots, one of which was identified as heat shock protein 70 (Hsp70) by MALDI-TOF/TOF-MS. Concentrations of serum Hsp70 autoantibody were significantly higher for patients with ESCC (mean, 0.412+/-0.096 mg/ml) than for patients with gastric (0.236+/-0.112 mg/ml, P<0.001) or colon cancer (0.231+/-0.120 mg/ml, P<0.001) or healthy individuals (0.207+/-0.055 mg/ml, P<0.001) by enzyme-linked immunosorbent assay. We have identified an autoantibody against Hsp70 in ESCC patients. The proteomic approach implemented herein offers a powerful tool for identifying novel serum markers that may display clinical utility against cancer.

Evaluation of lymph node metastases in gastric cancer using magnetic resonance imaging with ultrasmall superparamagnetic iron oxide (USPIO): diagnostic performance in post-contrast images using new diagnostic criteria.

BACKGROUND: We assessed the value of magnetic resonance imaging (MRI), using ultrasmall superparamagnetic iron oxide (USPIO) with new diagnostic criteria, in the evaluation of regional lymph node metastases in gastric cancer. METHODS: Thirty-one patients with gastric cancer were enrolled. 1000 lymph nodes were dissected during surgery, and of these, 519 nodes (51.9%) were identified by currently used MRI imaging analysis. We evaluated lymph nodes on USPIO-post-contrast T2*-weighted images using the following two criteria: (1) we diagnosed the nodes on T2*-weighted images according to conventional criteria, where a node having an overall low signal intensity (pattern A) was nonmetastatic, while a node having partial (pattern B) or overall (pattern C) high signal intensity was metastatic; (2) we subdivided pattern B nodes on T1-weighted images using the new criteria, in which a node for which the high-intensity area on T2*-weighted images was not defined as adipose tissue on T1-weighted images (pattern B1) was metastatic, while a node for which the high-intensity area was defined as adipose tissue (pattern B2) was nonmetastatic. RESULTS: (1) The results using the conventional criteria were 96.2% sensitivity, 92.5% specificity, 76.3% positive predictive value (PPV), 99.0% negative predictive value (NPV), and 93.3% accuracy. (2) The results using the new criteria were 96.2% sensitivity, 98.3% specificity, 90.1% PPV, 99.0% NPV, and 97.1% accuracy. CONCLUSION: The assessment of lymph node metastases from USPIO-post-contrast MRI alone using the new criteria was useful in the diagnosis of regional lymph node metastases in gastric cancer.

Proteomics-based approach identifying autoantibody against peroxiredoxin VI as a novel serum marker in esophageal squamous cell carcinoma.

PURPOSE: Detection of novel tumor-related antigens and autoantibodies will aid in diagnosis of early-stage cancer and in development of more effective immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (TE-2) and related autoantibodies in sera from patients with ESCC using a proteomics-based approach. EXPERIMENTAL DESIGN: TE-2 proteins were separated by two-dimensional PAGE, followed by Western blot analysis in which sera of patients with ESCC, healthy controls, and patients with other cancers were tested for primary antibodies. Positive spots were excised from silver-stained gels and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS). RESULTS: Sera from patients with ESCC yielded multiple spots, one of which was identified as peroxiredoxin (Prx) VI by MALDI-TOF/TOF MS. Western blot analysis against recombinant Prx VI showed reactivity in sera from 15 of 30 (50%) patients with ESCC and 2 of 30 (6.6%) healthy individuals. Autoantibody against Prx VI was found in sera from 1 of 30 (3.3%) patients with other types of cancer (colon cancer). CONCLUSION: We have identified for the first time an autoantibody against Prx VI in ESCC patients. The proteomic approach implemented here offers a powerful tool for identifying novel serum markers that may display clinical usefulness against cancer.

Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10.

BACKGROUND: Knowledge regarding the presence and location of lymph node metastasis in gastric cancer is essential in deciding on the operative approach. Lymph node metastases have been diagnosed with imaging tests such as computed tomography (CT) and ultrasonography (US); however, the accuracy of such diagnoses, based on size and shape criteria, has not been adequate. Ferumoxtran-10 (Combidex; Advanced Magnetics) is a lymphotropic contrast agent for magnetic resonance imaging (MRI) whose efficacy for the detection of metastatic lymph nodes in various cancers has been reported by several investigators; however, its efficacy for this purpose has not been reported for gastric cancer. We investigated the efficacy of ferumoxtran-10-enhanced MRI for the diagnosis of metastases to lymph nodes in gastric cancer. METHODS: Seventeen consecutive patients who were diagnosed with a nonearly stage of gastric cancer were enrolled in the study. All the patients were examined by MRI (Signa Horizon 1.5 T; GE Medical; T2*-weighted images) before and 24 h after the intravenous administration of ultrasmall particles of superparamagnetic iron oxide--ferumoxtran-10 (2.6 mg Fe/kg of body weight)--and the presence or absence of metastasis was determined from the enhancement patterns. The imaging results were compared with the corresponding histopathological findings following surgery. RESULTS: Of 781 lymph nodes dissected during surgery, the imaging results of 194 nodes could be correlated with their histopathological findings. Fifty-nine lymph nodes from 11 patients had histopathological metastases. In nonaffected normal lymph nodes, we observed dark signal intensity on MRI caused by the diffuse uptake of the contrast medium by macrophages resident in the lymph nodes, which phagocytose the iron oxide particles of ferumoxtran-10. The number of phagocytic macrophages was decreased in metastatic lymph nodes, and they showed various patterns of decreased uptake of ferumoxtran-10. Three enhancement patterns were observed in lymph nodes: (A) lymph nodes with overall dark signal intensity due to the diffuse uptake of ferumoxtran-10; (B) lymph nodes with partial high signal intensity due to partial uptake; and (C) no blackening of lymph nodes due to no uptake of ferumoxtran-10. Patterns (B) and (C) were defined as metastatic. The sensitivity, specificity, positive predictive value, negative predictive value, and overall predictive accuracy of postcontrast MRI were 100% (59/59), 92.6% (125/135), 85.5% (59/69), 100% (125/125), and 94.8% (184/194), respectively. These parameters for predictive accuracy were much superior to these parameters previously evaluated by CT or US. Nodes in the retroperitoneal and paraaortic regions were more readily identified and diagnosed on the MR images than those in the perigastric region. CONCLUSION: The present study confirmed that ferumoxtran-10-enhanced MRI is useful in the diagnosis of metastatic lymph nodes and that the use of this modality will be helpful in treatment decision-making for gastric cancer patients.

Familial cancer associated with a polymorphism in ARLTS1.

BACKGROUND: The finding of hemizygous or homozygous deletions at band 14 on chromosome 13 in a variety of neoplasms suggests the presence of a tumor-suppressor locus telomeric to the RB1 gene. METHODS: We studied samples from 216 patients with various types of sporadic tumors or idiopathic pancytopenia, peripheral-blood samples from 109 patients with familial cancer or multiple cancers, and control blood samples from 475 healthy people or patients with diseases other than cancer. We performed functional studies of cell lines lacking ARLTS1 expression with the use of both the full-length ARLTS1 gene and a truncated variant. RESULTS: We found a gene at 13q14, ARLTS1, a member of the ADP-ribosylation factor family, with properties of a tumor-suppressor gene. We analyzed 800 DNA samples from tumors and blood cells from patients with sporadic or familial cancer and controls and found that the frequency of a nonsense polymorphism, G446A (Trp149Stop), was similar in controls and patients with sporadic tumors but was significantly more common among patients with familial cancer than among those in the other two groups (P=0.02; odds ratio, 5.7; 95 percent confidence interval, 1.3 to 24.8). ARLTS1 was down-regulated by promoter methylation in 25 percent of the primary tumors we analyzed. Transfection of wild-type ARLTS1 into A549 lung-cancer cells suppressed tumor formation in immunodeficient mice and induced apoptosis, whereas transfection of truncated ARLTS1 had a limited effect on apoptosis and tumor suppression. Microarray analysis revealed that the wild-type and Trp149Stop-transfected clones had different expression profiles. CONCLUSIONS: A genetic variant of ARLTS1 predisposes patients to familial cancer.

A secure technique of intracorporeal Roux-Y reconstruction after laparoscopic distal gastrectomy.

BACKGROUND: Laparoscopic distal gastrectomy [LDG] is a minimally invasive surgery for gastric carcinoma. The Billroth I method has been commonly employed to reconstruct alimentary tract after LDG. Conversely, Roux-Y reconstruction is employed far less commonly despite its merits. Technical difficulties, including a risk of twisting the Roux loop under limited vision through a laparoscope, have hampered Roux-Y reconstruction after LDG. METHODS: We performed LDG and intracorporeal Roux-Y reconstruction in 5 patients with early gastric cancer. The procedure included a functional end-to-end anastmosis of the stomach and jejunum, consisting of side-to-side approximation of jejunal loop to greater curvature of the gastric remnant with a laparoscopic stapling device followed by closure of the open end and simultaneous division of the jejunum with another stapler. RESULTS: Roux-Y reconstruction was successfully accomplished without torsion of the loop in all patients. CONCLUSIONS: By using the present technique, intracorporeal Roux-Y reconstruction after LDG can be accomplished without a risk of twisting the jejunal loop.

Prognostic significance and different properties of survivin splicing variants in gastric cancer.

Survivin, a novel antiapoptosis gene, was identified as a member of the inhibitor of apoptosis protein (IAP) family. Unique among IAP, survivin has been found to be abundantly expressed in a wide variety of human malignancies, whereas it is undetectable in normal adult tissues. Recently, three splicing variants of survivin have been further characterized with different subcellular localization, but their different functions in carcinogenesis are largely unknown. We used real time quantitative RT-PCR to analyse survivin variants' mRNA expression levels in 77 gastric carcinoma cases whose frozen samples were available. All the cases and seven cell lines tested expressed wild-type survivin mRNA, which was not only the dominant transcript, but also was a poor prognostic biomarker (P = 0.003). Non-antiapoptosis survivin-2B mRNA was negatively correlated with tumor stage (P = 0.001) histological type (P = 0.007) and depth of tumor invasion (P = 0.031) while survivin-DeltaEx3 mRNA showed a significant reverse association with apoptosis ( P = 0.019). These data demonstrated that survivin mRNA expression levels are of important prognostic value, suggesting the significant participation of survivin-2B and survivin-DeltaEx3 in gastric cancer development.

Postoperative evaluation of the jejunal pouch reconstruction following proximal and distal gastrectomy for cancer.

BACKGROUND/AIMS: To evaluate the efficacy of the jejunal pouch reconstruction following subtotal proximal and distal gastrectomy, a retrospective study examining the postoperative condition of patients who underwent different methods of reconstruction after gastrectomy for cancer was undertaken. METHODOLOGY: Various parameters indicative of postoperative function were evaluated at one year postoperatively, and two major groups were examined. The "proximal gastrectomy" group was composed of patients who underwent either 1) proximal gastrectomy with an interposed jejunal pouch (PG-pouch), 2) proximal gastrectomy with simple jejunal interposition (PG-inter), or 3) total gastrectomy with simple jejunal interposition (TG). The "distal gastrectomy" group was composed of patients who underwent either 4) distal gastrectomy with an interposed jejunal pouch (DG-pouch), 5) distal gastrectomy with simple jejunal interposition (DG-inter), or 6) distal gastrectomy with Billroth 1 reconstruction (B-1). RESULTS: Volume of meal intake was better preserved and the incidence of abdominal symptoms were less frequent in the PG-pouch and DG-pouch groups. In the PG-inter, DG-inter and DG-pouch groups, none of the patients experienced heartburn or had endoscopic findings consistent with reflux esophagitis, while 2 patients (20.0%) in the PG-pouch group complained of heartburn with evidence of reflux esophagitis on endoscopy. Increase in blood acetaminophen level was milder in both the PG-pouch and DG-pouch groups, signifying improved gastric emptying. CONCLUSIONS: The jejunal pouch interposition following proximal and distal gastrectomy seems to confer clinical benefit in terms of postoperative function, especially in the form of meal intake, abdominal symptoms, and gastric emptying. The side effect of an improved reservoir may be the incidence of reflux esophagitis seen in 2 patients in the PG-pouch group.

[Fusion imaging of three-dimensional angiographies of arteries and veins around the stomach by multiphase fusion technique under single breath-hold using 16-detector multislice CT].

Postcontrast CT scan using multislice CT was performed in 10 patients prior to laparoscopic gastric cancer surgery. Using 16-detector multislice CT, images were obtained at both arterial and venous phases under a single breath-hold. Three-dimensional CT angiography at arterial and venous phases was respectively reconstructed using the volume-rendering technique and then fused. Multiphase fusion imaging was able to demonstrate clearly, simultaneously, and three-dimensionally the gastric arteries and veins without a respiratory gap. In conclusion, multiphase fusion images were considered to be very useful for the intraoperative navigation of laparoscopic gastric cancer surgery.

Preoperative simulation of vascular anatomy by three-dimensional computed tomography imaging in laparoscopic gastric cancer surgery.

BACKGROUND: Treatment of early gastric cancer may be an ideal application for laparoscopic surgery. But laparoscopic surgery has various limitations derived from the lack of tactile feedback and a two-dimensional display of the operative field. So, laparoscopic surgery is technically challenging and requires a more detailed understanding of local anatomy than conventional open surgery does. The purpose of this study was to evaluate the value of three-dimensional computed tomography imaging in the preoperative simulation of laparoscopic gastric cancer surgery. STUDY DESIGN: Multidetector-row helical CT was performed preoperatively in 49 patients who underwent laparoscopic gastric cancer surgery. Scanning was initiated approximately 20 seconds after an intravenous injection of 100 mL of contrast material at 5 mL/second. Three-dimensional CT images were reconstructed using the volume-rendering technique. RESULTS: 3D-CT imaging depicted the stomach, arterial, and venous anatomy and was able to identify important vascular variants. Preoperative information concerning the right gastric artery led us to the site of its branching and facilitated dissection of suprapyloric lymph nodes. The left gastric artery furnishing the aberrant left hepatic artery was successfully revealed and this information enabled us to avoid accidental hemorrhage and ischemic liver damage. Preoperative confirmation of the drainage routes of the left gastric vein was also useful in accomplishing secure lymphadenectomy. CONCLUSIONS: 3D-CT imaging provides a vascular "road map," which is critical for surgical guidance, and prevents the risks involved in surgery. Preoperative 3D-CT imaging may be an informative device to overcome the disadvantages of laparoscopic gastric cancer surgery.

Postoperative evaluation of function-preserving gastrectomy for early gastric cancer.

BACKGROUND/AIMS: We evaluated the efficacy of the following three surgical options in gastrectomy for early gastric cancer; 1) reduction of the extent of gastrectomy, 2) preservation of the vagal nerve, and 3) preservation of the pylorus. METHODOLOGY: The postoperative physical conditions of patients who had undergone 6 kinds of operating methods incorporating elements 1), 2) and 3) were compared. The efficacy of elements 1) and 3) was evaluated by comparison among a 2/3 proximal gastrectomy group (2/3-PG group, n = 5), 4/5 proximal gastrectomy group (4/5-PG group, n = 7), and total gastrectomy group (TG group, n = 12). The efficacy of elements 1), 2) and 3) was also evaluated by comparison among a pylorus-preserving gastrectomy (PPG) group with preservation of the vagal nerve (PPGV group, n = 15), 2/3 distal gastrectomy group with preservation of the vagal nerve (2/3-DGV group, n = 12), and 4/5 distal gastrectomy group without preservation of the vagal nerve (4/5-DG group, n = 15). RESULTS: Body weight loss and the incidence of abdominal symptoms and anemia in the 2/3-PG group, PPGV or 2/3-DGV group were less frequent than in the TG group or 4/5-DG group. The increases in acetaminophen concentration in the 2/3-PG group, PPGV or 2/3-DGV groups, and the changes in blood sugar and insulin levels in the 2/3-PG or PPGV group were modest, while hypergastrinemia in the 2/3-PG group was remarkable. The insulinogenic index was high in the 2/3-DGV group, and the plasma cholecystokinin changes and contraction pattern of the gallbladder resembled their preoperative pattern in the PPGV and 2/3-DGV groups. These results indicated that the patients in the 2/3-PG group owed their benefits to elements 1) and 3), the 2/3-DGV group to elements 1) and 2), and the PPGV group to elements 1), 2) and 3). CONCLUSIONS: Three surgical options in gastrectomy procedures for early gastric cancer, 1) reduction of the extent of gastrectomy, 2) preservation of the vagal nerve, and 3) preservation of the pylorus, were individually confirmed to have benefits for better postoperative quality of life.

Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas.

DCs are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation-specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti-CD1a antibody for immature DCs and an anti-CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a(+) TIDCs, and 82 (63.1%) samples contained CD83(+) TIDCs. The number of CD83(+) TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF-beta, whereas the number of CD1a(+) TIDCs was not. Kaplan-Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83(+) TIDCs with longer relapse-free (p = 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83(+) TIDCs was significantly better than that of patients with fewer CD83(+) TIDCs. Multivariate analysis revealed that CD83(+) TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer.