Identification of a novel SEREX antigen family, ECSA, in esophageal squamous cell carcinoma.

BACKGROUND: Diagnosis of esophageal squamous cell carcinoma (SCC) may improve with early diagnosis. Currently it is difficult to diagnose SCC in the early stage because there is a limited number of tumor markers available. RESULTS: Fifty-two esophageal SCC SEREX antigens were identified by SEREX (serological identification of antigens by recombinant cDNA expression cloning) using a cDNA phage library and sera of patients with esophageal SCC. Sequence analysis revealed that three of these antigens were similar in amino acid sequences, and they were designated as ECSA (esophageal carcinoma SEREX antigen)-1, -2 and -3. The ECSA family was also similar to an EST clone, hepatocellular carcinoma-associated antigen 25a (HCA25a). Serum antibody levels to ECSA-1, -2 and -3 were significantly higher in patients with esophageal SCC than in healthy donors. Based on the conserved amino acid sequences, three peptides were synthesized and used for enzyme-linked immunosorbent assays (ELISA). The serum antibody levels against one of these peptides were significantly higher in patients with esophageal SCC. This peptide sequence was also conserved in FAM119A, GOSR1 and BBS5, suggesting that these are also ECSA family members. Reverse transcription followed by quantitative PCR analysis showed that the mRNA expression levels of ECSA-1, -2 and -3 and FAM119A but not of HCA25a, GOSR1 and BBS5 were frequently elevated in esophageal SCC tissues. CONCLUSIONS: We have identified a new gene family designated ECSA. Serum antibodies against the conserved domain of the ECSA family may be a promising tumor marker for esophageal SCC.

Calpain regulates thymidylate synthase-5-fluoro-dUMP complex levels associated with response to 5-fluorouracil in gastric cancer cells.

Thymidylate synthase (TS) plays a major role in the response to 5-fluorouracil (5-FU) by binding directly to the 5-FU metabolite, 5-fluoro-dUMP (FdUMP). The change in the TS expression levels after 5-FU administration was examined in parallel to 5-FU responsiveness in six human gastric adenocarcinoma cell lines to elucidate the source of variability of 5-FU sensitivity. MKN-1, SH-10-TC and MKN-74 cells were more resistant to 5-FU than MKN-28, KATO III and MKN-45 cells. Western blotting analysis revealed that the 5-FU sensitivity of these cells did not correlate with the basal TS expression levels but did correlate with rapid detection of the TS-FdUMP complex after exposure to 5-FU. In 5-FU-resistant cells, very low levels of the TS-FdUMP complex early after 5-FU exposure were elevated by pretreatment with calpain inhibitors such as benzyloxycarbonyl-leucyl-leucinal (ZLLH), benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLH) and ALLN, but not by other protease inhibitors. In contrast, ONO-3403, which causes calpain activation, stimulated downregulation of the TS-FdUMP complex in 5-FU-sensitive cells. The expression levels of calpastatin, an endogenous calpain inhibitor, were higher in 5-FU-sensitive cells than in 5-FU-resistant cells. ZLLH increased the 5-FU sensitivity of 5-FU-resistant cells, whereas ONO-3403 decreased the sensitivity of 5-FU-sensitive cells. In addition, knockdown of m-calpain by siRNA increased the 5-FU sensitivity in 5-FU-resistant cells, while knockdown of calpastatin reduced the sensitivity in 5-FU-sensitive cells. These results suggest that calpain might reduce the chemosensitivity of human gastric cancer cells to 5-FU possibly by rapid degradation of the TS-FdUMP complex, a finding that is considered to have novel therapeutic implications.

Carbon-ion beam treatment induces systemic antitumor immunity against murine squamous cell carcinoma.

BACKGROUND: Carbon-ion beam (CIB) treatment is a powerful tool for controlling primary tumors in the clinical setting. However, to date, few clinical or experimental studies have investigated the effects of CIB treatment on tumor recurrence and antitumor immunity. METHODS: A multiple challenge test was performed using syngenic and nude mouse models of a poorly immunogenic squamous cell carcinoma cell line (SCCVII) after CIB treatment at a clinically available dose (77 kiloelectron volts [keV]/microm) to primary tumors. To further examine changes in antitumor immunity in this model, the authors used dendritic cell (DC)-based immunotherapy. RESULTS: In a syngenic model, CIB treatment itself resulted not only in efficient elimination of the primary tumor but also in a dramatic reduction of tumor formation after secondary tumor challenge at a contralateral site (P<.0001). Conversely, CIB treatment eliminated neither the primary nor the secondary tumor in nude mice. This antitumor effect produced by CIB treatment was enhanced significantly by combining it with DC immunotherapy (P=.0007). Combined CIB and DC treatment induced more intense cytolytic activity than CIB in a chromium-release assay. The third challenge tests, which included challenge with a third-party tumor cell line (FM3A) and effector depletion, revealed that the antitumor effects were the results of tumor-specific, long-lasting antitumor immunity through CD8-positive T lymphocytes. CONCLUSIONS: To the authors' knowledge, this is the first demonstration of strong antitumor immunity induced by CIB treatment in a dermal tumor, and this effect was enhanced by combining it with DC-based immunotherapy. The authors concluded that this combination warrants further investigation as a promising modality for the prevention of tumor recurrence.

BCL2L10 is frequently silenced by promoter hypermethylation in gastric cancer.

In gastric cancer, several tumor suppressor and tumor-related genes are silenced by aberrant methylation. Previously, we demonstrated that BCL2L10, which belongs to the pro-apoptotic Bcl-2 family, was transcriptionally repressed by promoter hypermethylation and that its overexpression caused apoptosis and growth inhibition of gastric cancer cells. In this study, we investigated the methylation status of BCL2L10 and its expression in 21 gastric cancer tissues and corresponding non-neoplastic mucosae along with the methylation status of p16, RUNX3, and hMLH1 genes by using methylation specific PCR. In addition, we examined the association between the methylation status of each gene and the expression of EZH2, which was associated with DNA methylation of its target genes. As a result, aberrant methylation of BCL2L10 was detected in 38% of gastric cancer and in 24% of corresponding non-neoplastic mucosae and correlated with low expression of BCL2L10. Methylation of p16, RUNX3, and hMLH1 was found in gastric cancer and in corresponding non-neoplastic mucosae at almost similar frequencies as previous reports. Expression of EZH2 was detected more frequently in tumors (48%) as compared to corresponding non-neoplastic mucosae (10%) (p=0.006), however, no significant difference was found between expression of EZH2 and the methylation frequency of each gene. In conclusion, our data suggest that silencing of BCL2L10 by aberrant methylation is a common feature in gastric cancer and its inactivation may be involved in the early steps of gastric carcinogenesis.

Viral shedding after p53 adenoviral gene therapy in 10 cases of esophageal cancer.

We detected adenoviral DNA fragments in excretions of 10 esophageal cancer patients by DNA-PCR after tumor injection of Ad-CMV-vector. A total of 220 samples consisting of feces, gargling saliva, urine, and blood plasma were assessed. A total of 29.7% of feces samples and 13.2% of gargling saliva samples were positive for adenoviral DNA fragments, but 89.7% of the positive feces samples and all of the positive gargling saliva samples turned negative on day 12 after tumor injection. Although adenoviral DNA fragments may be pathogen-free, patients' feces and gargling saliva contain adenoviral DNA fragments for 12 days after injection.

A kelch family protein Nd1-L functions as a metastasis suppressor in cancer cells via Rho family proteins mediated mechanism.

The BTB-kelch protein Nd1-L acts as an actin cytoskeleton stabilizer expressed ubiquitously in mouse tissues. We examined the effect of Nd1-L on cancer cell invasion and metastasis. Over-expression of Nd1-L in murine colon carcinoma cell line Colon 26 and murine melanoma cell line B16 resulted in suppression of pulmonary and liver metastasis after inoculation of these cells to syngeneric mice and in increased survival in an animal model. On the other hand, knock down of Nd1-L by RNA interference promoted metastasis ability of these cells. Increased expression of Nd1-L inhibited migration and Matrigel invasion capacity of cancer cell lines in vitro. Thus, Nd1-L expression inversely correlated with invasive and metastasis capacity of cancer cells. Furthermore, increased expression of Nd1-L in NIH3T3 cells inhibited growth factor induced activation of Rho family small GTPases such as Rho, Rac and cdc42. These results suggest that Nd1-L is involved in invasion and metastasis of cancer cells by regulating the actin cytoskeleton and Rho family proteins.

Identification of Makorin 1 as a novel SEREX antigen of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (SCC) represents one of the most malignant tumors. To improve the poor prognosis, it is necessary to diagnose esophageal SCC at early stages using new tumor markers. SEREX (serological identification of antigens by recombinant cDNA expression cloning) is suitable for large-scale screening of tumor antigens and has been applied for various types of human tumors. METHODS: Tumor markers of esophageal squamous cell carcinoma (SCC) were screened by SEREX method. The presence of serum anti-makorin 1 (MKRN1) antibodies (s-MKRN1-Abs) was examined by Western blotting using bacterially expressed MKRN1 protein. The expression levels of MKRN1 mRNA in tissues were examined by RT-PCR. The biological activity of MKRN1 was examined by transfection of ras-NIH3T3 mouse fibroblasts with MKRN1 cDNA. Major ubiquitinated proteins in MKRN1-transfected cells were identified by immunoprecipitation with anti-ubiquitin antibody followed by mass spectrometry. RESULTS: MKRN1 was identified as a novel SEREX antigen of esophageal SCC. Although a total of 18 (25%) of 73 patients with esophageal SCC had s-MKRN1-Abs, none of the 43 healthy donors had a detectable level of s-MKRN1-Abs. There was no correlation between the presence of s-MKRN1-Abs and clinicopathological variables other than histological grading. Well-differentiated tumors were associated significantly with the presence of s-MKRN1-Abs in the patients. The mRNA levels of MKRN1 were frequently higher in esophageal SCC tissues than in the peripheral normal esophageal mucosa. Stable transfection of ras-NIH3T3 cells with MKRN1 cDNA induced prominent morphological changes such as enlargement of the cell body and spreading. Ubiquitination of 80- and 82-kDa proteins were clearly observed in MKRN1-transfected cells but not in the parental cells, which were identified as L-FILIP (filamin A interacting protein 1). CONCLUSION: MKRN1 is a novel SEREX antigen of esophageal SCC, and s-NKRN1-Abs can be a candidate of diagnostic markers of esophageal SCC with high specificity. It is plausible that MKRN1 is involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of L-FILIP.

c-myc suppressor FBP-interacting repressor for cancer diagnosis and therapy.

Based on the genetic background of cancer, we have been trying to develop novel diagnostic and therapeutic strategies against human cancers. c-myc gene activation has been detected in many human cancers, indicating a key role of c-myc in tumor development. Thus targeting c-myc gene suppression is a promising strategy for cancer treatment. Recently, an interaction between FIR (FUSE-Binding Protein-Interacting Repressor) and TFIIH/p89/XPB helicase was found to repress c-myc transcription and so might be important for suppressing tumor formation. Previously, we have shown that the expression of splicing variant of FIR is elevated in colorectal cancer tissues and promotes tumor development by disabling FIR-repression to sustain high levels of c-Myc, opposing apoptosis in cancer cells. In this study, FIR recombinant adenovirus vector induces tumor growth suppression against tumor xenografts in animal model experiment. Together, one clue to the development of cancer diagnosis and therapies directed against c-Myc may go through FIR and its splicing variant.

Decrease in chemosensitivity against anticancer drugs by an esophageal squamous cell carcinoma SEREX antigen, AISEC.

We performed SEREX (serological identification of antigens by recombinant cDNA expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and examined whether some of the SEREX antigens can affect chemosensitivity against anticancer drugs. We isolated a novel gene which was designated as AISEC (antigen identified by SEREX for esophageal carcinoma). RT-PCR analysis showed that the mRNA expression levels of AISEC were higher in esophageal SCC tissues than in their normal counterparts. By transfection into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts, we isolated a clone, FAISEC-3, which stably expressed AISEC. FAISEC-3 cells were more resistant to anticancer drugs, such as mitomycin C, ifosfamide, vincristine, camptothecin and etoposide, than parental ras-NIH cells. Luciferase reporter assay after a transient transfection with AISEC cDNA or the control vector revealed that the transactivity of p53 was suppressed by AISEC in a dose-dependent manner. These results suggested that esophageal SCC tissues produce AISEC in increased amounts, which can reduce the chemosensitivity against anticancer drugs possibly by suppressing the p53 transactivation ability.

Perioperative changes of serum p53 antibody titer is a predictor for survival in patients with esophageal squamous cell carcinoma.

BACKGROUND: Although the presence of serum p53 antibody (s-p53-Abs) before treatment has been shown to correlate with poor prognosis and lymph node metastasis in esophageal cancer, there has been little information about postoperative s-p53-Abs titer and perioperative changes of s-p53-Abs titers in patients with esophageal carcinoma. METHODS: A highly specific enzyme-linked immunosorbent assay was used to analyze s-p53-Abs in 110 patients with esophageal squamous cell carcinoma before and 1 month after surgery. The cutoff level of 1.3 U/ml was used to indicate seropositive patients. Impact of postoperative s-p53-Abs titer and perioperative changes of s-p53-Abs on survival was evaluated. RESULTS: Forty (36%) of 110 patients were positive for s-p53-Abs before surgery and 35 patients (32%) were positive after surgery. s-p53-Abs titer generally decreased after surgery. Among sero-positive patients, the patients who remained sero-positive after surgery (n = 28) had a worse prognosis than patients who showed sero-conversion (P = 0.02). Among sero-positive patients, the nondecreased titer group showed significantly unfavorable survival (P < 0.01). Multivariate analysis revealed that postoperative s-p53-Abs was an independent risk factor for worse overall survival (adjusted hazard ratio = 3.05; 95% confidence interval = 1.11-8.33; P = 0.03). CONCLUSIONS: Perioperative monitoring of s-p53-Abs titers was useful to identify patients with esophageal cancer with a high risk for tumor recurrence and a poor prognosis. Continuous sero-positive patients and/or nondecreased titer group, even after surgery, showed significantly unfavorable survival.

Combined effects of p53 gene therapy and leptomycin B in human esophageal squamous cell carcinoma.

BACKGROUND: p53 gene therapy has been examined in several clinical trials, however, the results of those trials have mostly been unsatisfactory due to the low efficacy of this therapy. Leptomycin B (LMB) is an antibiotic originally isolated from Streptomyces that has the ability to inhibit the export of proteins containing a nuclear export signal from the nucleus to the cytoplasm. Currently, it has been shown that p53 protein has a nuclear export signal. In this study, we assessed whether LMB augments the transduced p53 gene effect. METHODS: Antiproliferative effect of LMB was assessed in human esophageal squamous cancer cell lines. Accumulation of p53 protein into the nucleus by LMB was observed by fluorescence microscopy. The combined effect of p53 and LMB was evaluated in in vitro experiments. RESULTS: LMB induced cell death in a dose-dependent manner and p53 drastically accumulated in the nucleus after LMB treatment. The combinatory treatment of p53 gene and LMB significantly increases the efficiency compared to either agent alone. CONCLUSIONS: Our findings suggest that LMB has a potent ability to augment the effect of the tumor suppressor p53 in esophageal squamous cancer cell lines and that it is a promising component in p53 gene therapy.

Early primary duodenal carcinoma arising from Brunner's glands synchronously occurring with sigmoid colon carcinoma: report of a case.

We herein report a case of early primary duodenal carcinoma arising from Brunner's glands synchronously occurring with sigmoid colon carcinoma. A 65-year-old man with a 5-year history of diabetes mellitus and benign prostatic hypertrophy was admitted to our hospital to undergo a resection of sigmoid colon carcinoma in December 2000. Upper gastrointestinal endoscopy, which was performed as routine preoperative screening, revealed an elevated submucosal-tumor-like lesion with a shallow central depression in the anterior wall of the duodenal bulb. A partial duodenectomy with a partial gastrectomy including No. 5 and No. 6 lymph node dissection and a sigmoidectomy were thus performed. The patient's postoperative course was uneventful. The histopathology of the resected duodenal specimen revealed the tumor to be an adenocarcinoma arising from Brunner's glands. The patient has remained disease-free and has shown no relapse for 6 years postoperatively. Because duodenal carcinoma arising from Brunner's glands is very rare, we report our case with a review of 25 similar documented cases.

Effect of hyperbaric oxygen therapy on patients with adhesive intestinal obstruction associated with abdominal surgery who have failed to respond to more than 7 days of conservative treatment.

BACKGROUND/AIMS: To investigate the effects of hyperbaric oxygen (HBO) therapy on patients with adhesive intestinal obstruction who have failed to respond to more than 7 days of conservative treatment. METHODOLOGY: Six hundred eighty-five patients, who were admitted a total of 879 times for adhesive intestinal obstruction, were divided into groups according to the treatment and interval between the first day of the therapy and clinical symptoms of obstruction; tube decompression therapy within 7 days after appearance of clinical symptoms (Group I: n = 321), clinical symptoms that have persisted for less than 7 days before the start of HBO therapy (Group II: n = 498), and for more than 7 days (Group III: n = 60). RESULTS: The overall resolution and mortality rates in the cases of adhesive intestinal obstruction were 79.8% and 2.2% in Group I, 85.9% and 1.4% in Group II, and 81.7% and 1.6% in Group III, respectively. Group II had significantly better resolution rates than Group I (odds ratio 1.6, p < 0.02). CONCLUSIONS: HBO therapy may be useful in management of adhesive intestinal obstruction associated with abdominal surgery, even in patients who fail to respond to other conservative treatments. HBO therapy may be a preferred option for treatment of patients for whom surgery should be avoided.

Analysis of the methylation status of genes up-regulated by the demethylating agent, 5-aza-2'-deoxycytidine, in esophageal squamous cell carcinoma.

To determine the clinical significance of gene promoter methylation in esophageal squamous cell carcinoma (ESCC), we examined the promoter methylation status of genes showing elevated expression, as determined by DNA microarray-based transcriptomic analysis, in three ESCC cell lines (TE-1, TE-2, TE-10) after 5-aza-2'-deoxycytidine (DAC) treatment. We observed a high degree of DNA methylation within the promoter regions of three genes, namely cathepsin L2 (CTSL2), normal mucosa of esophagus specific 1 (NMES1), and fatty acid binding protein 5 (FABP5). Overexpression of NMES1 in ESCC cell lines increased cell motility. Down-regulation of NMES1 might play an important role in the cell motility of ESCC or be a potent marker of malignancy.

Gene therapy for esophageal squamous cell carcinoma.

Despite improvement of surgical treatment and application of multi-modality therapies to advanced esophageal cancer, the prognosis is extremely poor in patients with T4 tumors. Based on the genetic background of esophageal cancer, we have developed various gene therapy strategies against human esophageal cancer cells. In this article, we reviewed molecular events of esophageal cancer and gene therapy approaches for its treatment. First, we analyzed p53 genetic alterations and angiogenesis in esophageal cancer. Second, we evaluated an impact of p53 recombinant adenoviral vector (Ad5CMV-p53) on esophageal cancer cells. Significant growth suppression was observed following infection with Ad5CMV-p53 in human esophageal squamous cell carcinoma cell lines. This observation suggests that Ad5CMV-p53 may be a potentially effective therapeutic agent for locally advanced esophageal cancer. Promising avenues for investigation include double gene therapy and adjuvant use of gene therapy with radiation therapy. Third, we have performed a clinical study for p53 gene therapy for un-resectable advanced esophageal cancer. This clinical trial was planned to evaluate vector tolerability and efficacy. A total of 10 patients were enrolled into this phase I/II trial.

Role of histone deacetylase inhibitor in adenovirus-mediated p53 gene therapy in esophageal cancer.

BACKGROUND: Recently, the use of histone deacetylase inhibitors (HDACI) with gene therapy has been shown to improve the effect of this therapy. The effectiveness of one of the novel HDACIs, FK228, was examined in adenovirus-mediated p53 gene therapy of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The expression levels of coxsackie and adenovirus receptor (CAR) in ESCC patients were examined immunohistochemically. CAR induction by FK228 in ESCC cells was analyzed by real-time PCR and Western blotting. The efficiencies of adenoviral transduction treated with FK228 were determined using AV1.0CMV-betagal. The acetylation of p53 protein was detected by Western blotting. RESULTS: CAR expression was reduced in some tumor specimens compared to that in normal specimens. CAR expression was increased by FK228 in both in vitro and in vivo experiments. FK228 improved the efficiency of adenovirus infection. Acetylated p53 protein was increased in a dose- and a time-dependent manner. CONCLUSION: Our findings suggest that FK228 has a potent ability to augment the effect of adenovirus-mediated p53 gene therapy in ESCC cells.

Impact of preoperative dental plaque culture for predicting postoperative pneumonia in esophageal cancer patients.

BACKGROUND/AIMS: In esophageal cancer patients, postoperative pneumonia frequently occurs. In the oral cavity, dental plaque is a major reservoir of bacteria, and it is possible that oral bacteria are aspirated into the upper respiratory tract after esophagectomy. We evaluated the interaction between preoperative dental plaque and postoperative pneumonia in patients undergoing esophagectomy. PATIENTS AND METHODS: Thirty-nine patients with thoracic esophageal cancer who underwent esophagectomy were investigated. Preoperatively, dental plaque was collected and the bacterial flora investigated. If postoperative pneumonia occurred, the sputum was harvested and the pathogens were evaluated. RESULT: Postoperative pneumonia was observed in 14 patients (35.9%): 5 (71.4%) of 7 patients in the pathogen-positive group and 9 (28.1%) of 32 patients in the pathogen-negative group. In 2 (40.0%) of 5 patients with postoperative pneumonia, who had pathogenic bacteria in the preoperative dental plaque, the same pathogenic bacteria were also identified in the postoperative sputum. CONCLUSION: Pathogens in preoperative dental plaque are risk factors for postoperative pneumonia following thoracotomy in patients with thoracic esophageal cancer.

Have surgical outcomes of pathologic T4 esophageal squamous cell carcinoma really improved? Analysis of 268 cases during 45 years of experience.

BACKGROUND: Because invasion to an adjacent organ (T4) indicates highly advanced disease, and most surgeons avoid esophagectomy, the prognostic impact of clinicopathologic factors for survival of these patients after esophagectomy has rarely been analyzed. STUDY DESIGN: From 1960 to 2005, a total of 268 patients with esophageal squamous cell carcinoma underwent esophagectomy for pathologic T4 disease (pT4). The impact of clinicopathologic factors on survival was evaluated by univariate and multivariate analysis. Changes in surgical outcomes and longterm survival between the earlier period (1960 to 1989) and the later period (1990 to 2005) were analyzed. RESULTS: Overall survival rates of all patients were 25% at 1 year, 10% at 3 years, and 5% at 5 years. The survival curve of the later group was significantly better than that of the earlier group (p < 0.01). Multivariate analysis indicated that venous invasion (hazards ratio, 1.76; 95% CI, 1.33 to 2.33, p < 0.01) and presence of a postoperative complication (hazards ratio, 2.62; 95% CI, 1.96 to 3.51, p < 0.01) were independent risk factors for poor overall survival. Presence of residual cancer was also an independent risk factor for poor cause-specific survival (hazards ratio, 2.40; 95% CI, 1.23 to 4.69, p=0.01). Venous invasion and intramural metastasis were risk factors for residual cancer. A total of 38 (14%) patients, 15 in the early period and 23 in the later period, underwent complete resection (R0). Although overall survival after R0 resection in the later period improved slightly, cancer-related survival rates were similar in both periods. CONCLUSIONS: Although overall survival of patients with pT4 improved after 1990, this improvement might be mainly dependent on curability of the resection.

Preclinical assessment and pilot study using anti-CEA monoclonal antibody 1B2 for colorectal carcinoma imaging.

BACKGROUND/AIMS: Preclinical assessment of radio-labeled monoclonal antibodies is essential to the understanding of target-specific tumor localization. The purpose of this study is to prepare for fundamental evaluation of antibodies and to validate the clinical usefulness of the candidate considered useful for practice through preclinical assessment. METHODOLOGY: The immunoreactivity and affinity constant of three kinds of monoclonal antibody (1A4, 1B2, 4H11: CEA-specific) were evaluated with the method of cell binding assay. Tumor localization and biodisrtibution were performed in tumor-bearing athymic mice. Five patients of colorectal cancer underwent radioimmunodetection with 99mTc. Histological analysis was performed to evaluate the tumor localization of injected antibody. RESULTS: The immunoreactive fraction value of 1B2 is the highest than the other antibodies. The difference between the antibody affinities among three antibodies although were rather small. In an animal model, 1B2 obtained more highly tumor targeting and cleared more rapidly from the blood than the other two antibodies did. Pilot study using 1B2 was successful in all cases without background imaging. Visualization of tumor sites surgically removed revealed positive CEA and IgG immunostaining. CONCLUSION: The preparation for preclinical assessment of the characteristic parameters is practically valuable for clinical application of radiolabeled antibodies.

Hyperbaric oxygen therapy as a prophylactic and treatment against ileus and recurrent intestinal obstruction soon after surgery to relieve adhesive intestinal obstruction.

BACKGROUND AND AIM: Nonoperative management of cases of adhesive intestinal obstruction would be ideal, especially for patients who have recently undergone surgery to relieve the same condition. We aimed to examine whether hyperbaric oxygen (HBO) therapy might have therapeutic potential for the treatment of postoperative paralytic ileus and recurrent adhesive intestinal obstruction soon after surgery, to relieve adhesive intestinal obstruction, because of its unique mechanisms in these contexts. METHODS: A total of 133 patients were enrolled in the present study. We examined non-per os periods, hospital stay, and clinical course according to the postoperative course of the 133 patients. RESULTS: After surgical intervention, 75 patients left the hospital without morbidity. Nineteen patients were successfully administered prophylactic HBO therapy to facilitate intestinal motility and to prevent paralytic ileus. The remaining 39 patients suffered from postoperative paralytic ileus or early recurrence of obstruction during the same hospitalization period. The patients who underwent prophylactic HBO therapy had significantly shorter non-per os periods and hospital stays after surgery than those who were not initially given HBO therapy (P < 0.05). Similarly, there were significant differences in duration of hospital stay after surgery between patients with HBO therapy as treatment and those who received other conservative therapies (P < 0.05). CONCLUSIONS: HBO therapy may have a prophylactic effect on postoperative paralytic ileus and may be of therapeutic benefit in the management of early recurrent adhesive intestinal obstruction following surgery to relieve adhesive intestinal obstruction.