Comparative Study of Plan Robustness for Breast Radiotherapy: Volumetric Modulated Arc Therapy Plans with Robust Optimization versus Manual Flash Approach.

A previous study investigated robustness of manual flash (MF) and robust optimized (RO) volumetric modulated arc therapy plans for breast radiotherapy based on five patients in 2020 and indicated that the RO was more robust than the MF, although the MF is still current standard practice. The purpose of this study was to compare their plan robustness in terms of dose variation to clinical target volume (CTV) and organs at risk (OARs) based on a larger sample size. This was a retrospective study involving 34 female patients. Their plan robustness was evaluated based on measured volume/dose difference between nominal and worst scenarios (ΔV/ΔD) for each CTV and OARs parameter, with a smaller difference representing greater robustness. Paired sample t-test was used to compare their robustness values. All parameters (except CTV ΔD98%) of the RO approach had smaller ΔV/ΔD values than those of the MF. Also, the RO approach had statistically significantly smaller ΔV/ΔD values (p < 0.001-0.012) for all CTV parameters except the CTV ΔV95% and ΔD98% and heart ΔDmean. This study's results confirm that the RO approach was more robust than the MF in general. Although both techniques were able to generate clinically acceptable plans for breast radiotherapy, the RO could potentially improve workflow efficiency due to its simpler planning process.

Insulin deficiency promotes formation of toxic amyloid-ß42 conformer co-aggregating with hyper-phosphorylated tau oligomer in an Alzheimer's disease model.

The toxic conformer of amyloid ß-protein (Aß) ending at 42 (Aß42), which contains a unique turn conformation at amino acid residue positions 22 and 23 and tends to form oligomers that are neurotoxic, was reported to play a critical role in the pathomechanisms of Alzheimer's disease (AD), in which diabetes mellitus (DM)-like mechanisms are also suggested to be operative. It remains to be established whether the attenuation of insulin signaling is involved in an increase of toxic Aß42 conformer levels. The present study investigated the association between impaired insulin metabolism and formation of toxic Aß42 conformers in the brains of an AD mouse model. In particular, we studied whether insulin deficiency or resistance affected the formation of toxic Aß42 conformers in vivo. We induced insulin deficiency and resistance in 3xTg-AD mice, a mouse AD model harboring two familial AD-mutant APP (KM670/671NL) and PS1 (M146 V) genes and a mutant TAU (P301L) gene, by streptozotocin (STZ) injection and a high fructose diet (HFuD), respectively. Cognitive impairment was significantly worsened by STZ injection but not by HFuD. Dot blot analysis revealed significant increases in total Aß42 levels and the ratio of toxic Aß42 conformer/total Aß42 in STZ-treated mice compared with control and HFuD-fed mice. Immunostaining showed the accumulation of toxic Aß42 conformers and hyper-phosphorylated tau protein (p-tau), which was more prominent in the cortical and hippocampal neurons of STZ-treated mice compared with HFuD-fed and control mice. HFuD-fed mice showed only a mild-to-moderate increase of these proteins compared with controls. Toxic Aß42 conformers were co-localized with p-tau oligomers (Pearson's correlation coefficient = 0.62) in the hippocampus, indicating their co-aggregation. Toxic Aß42 conformer levels were inversely correlated with pancreatic insulin secretion capacity as shown by fasting immunoreactive insulin levels in STZ-treated mice (correlation coefficient = -0.5879, p = .04441), but not HFuD-fed mice, suggesting a decrease in serum insulin levels correlates with toxic Aß42 conformer formation. Levels of p-Akt and phosphorylated glycogen synthase kinase-3ß measured by a homogeneous time-resolved fluorescence assay were significantly lower in STZ-treated mice than in HFuD-fed mice, suggesting a greater inhibition of brain insulin signaling by STZ than HFuD, although both levels were significantly decreased in these groups compared with controls. Iba1-positive and NOS2-positive areas in the cortex and hippocampus were significantly increased in STZ-treated mice and to a lesser extent in HFuD-fed mice compared with controls. These findings suggest that insulin deficiency rather than insulin resistance and the resultant impairment of brain insulin signaling facilitates the formation of toxic Aß42 conformer and its co-aggregation with p-tau oligomers, and that insulin deficiency is an important pathogenic factor in the progression of AD.

Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease.

Apomorphine (APO) promotes intraneuronal amyloid-ß (Aß) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aß, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO. Protein levels of two types of serine-phosphorylated insulin receptor substrate-1 (IRS-1), pS616 and pS636/639, significantly decreased following APO treatment in the 13-month-old 3xTg-AD mice brain, suggesting improved brain insulin resistance. Immunostaining of the IDE, pS616 and pS636/639 IRS-1 demonstrated similar changes due to APO treatment. Thus, brain insulin resistance is considered an important therapeutic target in AD, and APO may provide improved neuronal insulin resistance.

Activation of TRPV4 strengthens the tight-junction barrier in human epidermal keratinocytes.

The transient receptor potential cation channel, subfamily V (TRPV), is expressed in the epidermis and considered to be a sensor of extrinsic stimuli such as temperature and other physical or chemical factors. In this study, we examined whether or not the activation of TRPVs by their agonists alters the epidermal tight junction (TJ) function in cultured human epidermal keratinocytes. Reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that mRNA for TRPV1, 3 and 4 were expressed in differentiated keratinocytes in which TJs had formed. Stimulation of the keratinocytes with a TRPV4 agonist (4α-phorbol 12, 13-didecanoate, 4α-PDD) strengthened the TJ-associated barrier, analyzed by means of transepithelial electric resistance measurements and flux measurements of the paracellular tracer. Stimulation with TRPV1 and TRPV3 agonists did not have the same result. Simultaneously, the 4α-PDD-stimulated keratinocytes showed an upregulation of TJ structural proteins, occludin and claudin-4, and TJ regulatory factors, phospho-atypical PKCζ/ι. It was also observed that the amounts of occludin and phospho-atypical PKCζ/ι complex were higher in 4α-PDD stimulated keratinocytes. In conclusion, we demonstrated that the activation of TRPV4 strengthened the TJ-associated barrier of epidermal cells. It was also suggested that the upregulation of TJ structural proteins and/or the posttranslational modification of TJ structural proteins by phospho-atypical PKCζ/ι are responsible for the enhancement of TJ function. Our study supports the hypothesis that TJs change their function in response to a change in the external environment sensed through TRPVs.

Activation of glutathione peroxidase and inhibition of p53-related apoptosis by apomorphine.

Apomorphine hydrochloride (APO) is known to be a dopamine receptor agonist, and has recently been found to be a novel drug for Alzheimer's disease (AD). We found that APO treatment ameliorated oxidative stress in an AD mouse model and specifically attenuated the hydrogen peroxide-induced p53-related apoptosis in the SH-SY5Y neuroblastoma cell line. To further understand the mechanism behind this action, we investigated the actions of APO on intracellular redox systems, such as the glutathione cycle and catalase. We studied the effects of specific inhibitors for glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (BCNU, MCS, and ATZ, respectively) on the effects of APO. Treatments with MCS or BCNU, but not ATZ, significantly attenuated the protective effects of APO. Interestingly, APO treatment elevated GPx activity, but did not increase the expression of the GPx1 protein. Although BCNU treatment attenuated APO effects, GR activity was not elevated by APO treatment. The same effects were observed in primary neuronal cultures. In addition, treatment with dopamine D1, D2, D3 and D4 receptor antagonists did not counteract the protective action of APO. Thus, APO may enhance GPx activity through dopamine receptor-independent pathways.

Down-regulation of single immunoglobulin interleukin-1R-related molecule (SIGIRR)/TIR8 expression in intestinal epithelial cells during inflammation.

Single immunoglobulin (Ig) interleukin-1R-related molecule (SIGIRR) is an Ig-like membrane protein critical for negative regulation of Toll-like receptor (TLR)-4-mediated signalling. We investigated SIGIRR expression and its regulation mechanism in intestinal epithelial cells (IECs) during inflammation. Endoscopic biopsy specimens were obtained from active and inactive colonic mucosa of ulcerative colitis (UC) patients, then SIGIRR expression was examined using real-time polymerase chain reaction (PCR) and immunohistochemistry (IH). Mice experimental colitis models were established by administrations of sulphonic acid (TNBS) and dextran sodium sulphate (DSS), and epithelial expression of SIGIRR was examined using real-time PCR, IH and flow cytometry. The effects of lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-α on SIGIRR expression were evaluated in vitro using cultured IECs. To elucidate SIGIRR expression regulation in IECs, binding ability of the transcription factor SP1 at the responsive element of the SIGIRR promoter was examined using gel-shift and chromatin immunoprecipitation (ChIP) assays. In human colonic samples, SIGIRR was expressed mainly in IECs at levels significantly higher in inactive compared to active mucosa. In the mice, SIGIRR colonic expression decreased rapidly after colitis development and returned gradually to basal levels. Experimental colitis-mediated down-regulation of SIGIRR in IECs was also confirmed by IH and flow cytometry results. Further, inflammatory conditions induced by TLR ligands and TNF-α caused significant down-regulation of SIGIRR expression in IECs, which was dependent upon decreased SP1 binding at the responsive element of the SIGIRR promoter. We found that SIGIRR is expressed in IECs and serves as a negative regulator to maintain gut innate immunity, which is down-regulated during inflammation by inhibition of an SP1-mediated pathway.

Evaluation of modified crystal violet chromoendoscopy procedure using new mucosal pit pattern classification for detection of Barrett's dysplastic lesions.

BACKGROUND: Pit pattern diagnosis is important for endoscopic detection of dysplastic Barrett's lesions, though using magnification endoscopy can be difficult and laborious. We investigated the usefulness of a modified crystal violet chromoendoscopy procedure and utilised a new pit pattern classification for diagnosis of dysplastic Barrett's lesions. METHODS: A total of 1,030 patients suspected of having a columnar lined oesophagus were examined, of whom 816 demonstrated a crystal violet-stained columnar lined oesophagus. The early group of patients underwent 0.05% crystal violet chromoendoscopy, while the later group was examined using 0.03% crystal violet with 3.0% acetate. A targeted biopsy of the columnar lined oesophagus was performed using crystal violet staining after making a diagnosis of closed or open type pit pattern with a newly proposed system of classification. The relationship between type of pit pattern and histologically identified dysplastic Barrett's lesions was evaluated. RESULTS: Dysplastic Barrett's lesions were identified in biopsy samples with an open type pit pattern with a sensitivity of 96.0%. Further, Barrett's mucosa with the intestinal predominant mucin phenotype was closely associated with the open type pit pattern (sensitivity 81.9%, specificity 95.6%). CONCLUSIONS: The new pit pattern classification for diagnosis of Barrett's mucosa was found to be useful for identification of cases with dysplastic lesions and possible malignant potential using a crystal violet chromoendoscopic procedure.

Melanoma recurrence patterns after negative sentinel lymphadenectomy.

HYPOTHESIS: A tumor-negative sentinel node (SN) does not eliminate the chance of melanoma recurrence. Patterns of metastasis can be identified and characterized in patients with tumor-negative SNs. DESIGN: Retrospective review. SETTING: Melanoma referral center. PATIENTS: Patients who underwent lymphatic mapping and sentinel lymphadenectomy between 1995 and 2002 and whose SNs were negative for metastasis by hematoxylin-eosin and immunohistochemistry staining were included in the study. The SN specimens from patients with recurrent disease were reexamined for missed metastasis. MAIN OUTCOME MEASURES: Differences in survival related to sites of recurrence and the rate of false-negative histopathologic SN diagnosis were determined. RESULTS: At a median follow-up of 36.7 months, 69 (8.9%) of 773 patients with tumor-negative SNs had recurrent disease. Three-year survival after first recurrence was 17.1% in the 37 patients with distant recurrence, 48.7% in the 19 patients with local or in-transit recurrence, and 63.5% in the 13 patients with regional basin recurrence; the difference in survival between patients with local or regional and distant recurrences was statistically significant (P<.001). Histopathologic reexamination of SNs from the 69 patients identified 9 patients with false-negative SNs; 2 of these had same-basin recurrences. CONCLUSIONS: The SN is a valuable prognostic indicator because only 8.9% of patients with tumor-negative SNs will develop recurrence. The low incidence (1.7%) of regional basin recurrence in patients with negative SNs supports the accuracy of our current method of lymphatic mapping and sentinel lymphadenectomy to identify occult regional nodal basin metastasis.

Barrett's oesophagus with predominant intestinal metaplasia correlates with superficial cyclo-oxygenase-2 expression, increased proliferation and reduced apoptosis: changes that are partially reversed by non-steroidal anti-inflammatory drugs usage.

BACKGROUND: Cyclo-oxygenase-2 expression has been reported to play an important role in the metaplasia-dysplasia-carcinoma sequence in Barrett's oesophagus. However, the existence of cyclo-oxygenase-2 expressing cells in Barrett's epithelium is still uncertain. AIM: To identify the cells that express cyclo-oxygenase-2 protein and to investigate the relationship between cyclo-oxygenase-2 expression and mucin-phenotype of Barrett's epithelium. METHODS: Sections from 466 biopsy samples of Barrett's epithelium from 358 non-medicated patients were immunohistochemically examined for the cyclo-oxygenase-2 expression, mucin-phenotype, cell proliferation and apoptosis. RESULTS: Cyclo-oxygenase-2 expression was detected in 71.0% of Barrett's epithelium biopsy samples. In Barrett's epithelium with the gastric predominant mucin-phenotype, cyclo-oxygenase-2 expression was mainly found in stromal and deep epithelial cells, whereas in intestinal predominant mucin-phenotype, it was mostly in superficial epithelial cell. A significant elevation of proliferating cell nuclear antigen index and suppression of apoptotic index was observed in Barrett's epithelium with superficial epithelial cyclo-oxygenase-2 expression. Neither such elevation of proliferating cell nuclear antigen index nor the suppression of apoptotic index could be found in chronic non-steroidal anti-inflammatory drugs users. CONCLUSIONS: Barrett's epithelium with intestinal mucin and superficial epithelial cyclo-oxygenase-2 expression possess a higher proliferation potential, but this risk may be thwarted by non-steroidal anti-inflammatory drugs administration.

Expression of midkine and receptor-like protein tyrosine phosphatase (RPTP)-beta genes in the rat stomach and the influence of rebamipide.

BACKGROUND: Midkine has been reported to bind to receptor-like protein tyrosine phosphatase (RPTP)-beta and to play important roles in growth and differentiation of various cells. Midkine is expressed in rat stomach during experimental ulcer healing, suggesting that the midkine-RPTP-beta system has some physiological functions in the stomach. Rebamipide is a mucoprotective drug used for the treatment of gastric ulcers. We have tested the hypothesis that the ulcer healing mechanism stimulated by rebamipide is linked physiologically to the gastric midkine-RPTP-beta system. MATERIALS AND METHODS: Seven-week-old-male Wistar rats were used. Midkine and RPTP-beta gene expression in rat stomach was investigated by laser capture microdissection coupled with the reverse transcription-polymerase chain reaction (RT-PCR). The effects of rebamipide on midkine and RPTP-beta expression in rat stomach and the gastric epithelial cell line RGM1 were evaluated by RT-PCR and Northern blot analyses. RESULTS: Midkine and RPTP-beta expression was detected in the gastric mucosal, submucosal and muscle layers. Rebamipide stimulated both midkine and RPTP-beta expression in rat stomach and RGM1 cells. CONCLUSION: Rebamipide may protect the gastric mucosa by regulating midkine and RPTP-beta expression.

[Three cases with a mediastinal neurinoma developed in a same family].

A 47-years-old woman (case 1) was admitted to our hospital because of a mediastinal mass. We performed an operation by VATS under the diagnosis of a mediastinal neurinoma. The histology of it was a neurinoma. Her father (case 2) had undergone a resection of a mediastinal neurinoma at the age of 42. Her brother (case 3) also had undergone a resection of mediastinal and intrathoracic neurinomas at the age of 37. A few years later, he underwent operations for neurinomas in limbs 2 times. We suppose patients with a mediastinal neurinoma have little complaints in many cases, so there are a number of patients who have a mediastinal neurinoma without being discovered and treated. Although the neurinoma is not considered as a hereditary disease inherently, the cases, we experienced, might have some genetic disorders. In this concern, our cases are very rare and have a great interest.

[Clinical efficacy of magnetic resonance cholangiopancreatography in the diagnosis of biliary tract diseases].

This study was carried out to clarify the efficacy of magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of biliary tract diseases, Three hundred and eleven patients who underwent MRCP and ERCP during the period from January 1999 to December 1999 at our institution were included in the study. Two gastroenterologists who were blinded to results of direct cholangiography and final diagnoses interpreted MRCP images prospectively. The biliary duct was visualized by MRCP and ERCP in 99.4% and 89.5% of the cases, respectively. The sensitivity, specificity, and accuracy of MRCP in the diagnosis of choledocholithiasis were 95%, 97%, and 97%, respectively. MRCP depicted the presence of strictures with a sensitivity, specificity, and accuracy of 97%, 96%, and 96%, respectively. There were three false-positive cases because of artifacts from arterial compression, The accuracy of MRCP and ERCP in differentiation of benign strictures from malignant ones was 85% and 96%, respectively. Based on these results, it is concluded that MRCP has high capability in visualization of the biliary tree, and in detection of stones and strictures, To avoid over and under-diagnosis, awareness of some pitfalls inherent in, MRCP is important. We suggest that MRCP should be recommended for patients with suspicion of biliary tract diseases in the initial stage of making diagnosis.

Novel site on sodium channel alpha-subunit responsible for the differential sensitivity of grayanotoxin in skeletal and cardiac muscle.

We searched for sites on the alpha-subunit of the fast Na(+) channel responsible for the difference in GTX (grayanotoxin) sensitivity of the skeletal- and cardiac-muscle Na(+) current. cDNA clones, encoding the skeletal or cardiac isoforms of the alpha-subunit, were inserted into a mammalian expression vector and transiently transfected into human embryonic kidney cells. The expressed channels were measured using whole-cell patch-clamp techniques and examined for GTX sensitivity. As a measure of GTX sensitivity, we used relative chord conductance (ratio of maximum chord conductance of noninactivating GTX-modified Na(+) currents to that of unmodified peak currents). Wild-type channels from skeletal muscle (mu 1) were more sensitive to GTX modification than wild-type cardiac channels (rH1) by a factor of 1.6. To facilitate exploration of alpha-subunit sites determining GTX sensitivity, we used SHHH, a chimera of skeletal muscle (S) domain D1 and heart muscle (H) domains D2D3D4 with supernormal sensitivity to GTX I (1.5-fold of wild-type mu 1). Successive replacement of Ser-251 (D1S4-S5 intracellular loop) and Ile-433 (D1S6 transmembrane segment), with corresponding rH1 residues Ala and Val, reduced, in a stepwise manner, the GTX sensitivity of the chimera and related mutants to that of wild-type rHl. We concluded that, in addition to Ile-433, known as the GTX-binding site, Ser-251 represents a novel site for GTX modification.

State-dependent action of grayanotoxin I on Na(+) channels in frog ventricular myocytes.

1. Distinct properties of grayanotoxin (GTX) among other lipid-soluble toxins were elucidated by quantitative analysis made on the Na(+) channel in frog ventricular myocytes. 2. GTX-modified current (I(GTX)) was induced strictly in proportion to the open probability of Na(+) channels during preconditioning pulses irrespective of its duration, amplitude or partial removal of inactivation by chloramine-T. This confirms that GTX binds to the Na(+) channel exclusively in its open state, while batrachotoxin (BTX) was reported to be capable of modifying slow-inactivated Na(+) channels, and veratridine exhibited voltage-dependent modification. 3. The GTX-modified channel did not show any inactivation property, which is different from reported results with veratridine and BTX. 4. Estimated unbinding rates of GTX were in reverse proportion to the activation curve of GTX-modified Na(+) channels. This was not the previously reported case with veratridine. 5. A model including unbinding kinetics of GTX and slow inactivation of unmodified Na(+) channels in which GTX was permitted to bind only to the open state of Na(+) channels indicated that unbinding reactions of GTX occur only in the closed state.

Pulmonary resection for metastases from colorectal cancer.

BACKGROUND: We reviewed our experience in the surgical treatment of 47 patients with colorectal pulmonary metastases and investigated factors affecting their survival. METHOD: From September 1986 to December 1999, 47 patients underwent 59 thoracotomies for pulmonary metastases from colorectal cancer. RESULTS: The median interval between colorectal resection and lung resection (disease-free interval [DFI]) was 33 months. Overall, 5-year survival was 48%. Five-year survival was 51% for patients with solitary metastasis (n = 30), 47% for patients with ipsilateral multiple metastases (n = 11), and 50% for patients with bilateral metastases (n = 6), and there were no significant differences. Five-year survival was 80.8% for 14 patients with DFI of < 2 years and 39.7% for 30 patients with a DFI of > 2 years (p = 0.22). Five-year survival for 11 patients with normal prethoracotomy carcinoembryonic antigen (CEA) levels was 70%, and that for 26 patients with elevated prethoracotomy CEA levels (> 5 ng/mL) was 36% (p < 0.05). Eight patients had extrathoracic disease. The median survival time after pulmonary resection was 18.5 months, and the 5-year survival was 60%. A second resection for recurrent metastases was performed in five patients, and a third resection was done in one patient. All six patients are alive. The median survival of five patients who underwent a second thoracotomy was 22 months (range, 2 to 68 months), and one patient is alive 39 months after the third resection. CONCLUSION: Pulmonary resection for metastases from colorectal cancer may help prolong survival in selected patients, even with bilateral lesions, recurrent metastasectomy, or extrathoracic disease. Prethoracotomy CEA level was found to be a significant prognostic factor.

An analysis of the variations in potency of grayanotoxin analogs in modifying frog sodium channels of differing subtypes.

Responses of tetrodotoxin-sensitive (TTX-s) and insensitive (TTX-i) Na(+) channels, in frog dorsal root ganglion (DRG) cells and frog heart Na(+) channels, to two grayanotoxin (GTX) analogs, GTX-I and alpha-dihydro-GTX-II, were examined using the patch clamp method. GTX-evoked modification occurred only when repetitive depolarizing pulses preceded a single test depolarization; modification, during the test pulse, was manifested by a decrease in peak Na(+) current accompanied by a sustained Na(+) current. GTX-evoked modification of whole-cell Na(+) currents was quantified by normalizing the conductance for sustained currents through GTX-modified Na(+) channels to that for the peak current through unmodified Na(+) channels. The dose-response relation for GTX-modified Na(+) channels was constructed by plotting the normalized slope conductance against GTX concentration. With respect to DRG TTX-i Na(+) channels, the EC(50) and maximal normalized slope conductance were estimated to be 31 microM and 0.23, respectively, for GTX-I, and 54 microM and 0.37, respectively, for alpha-dihydro-GTX-II. By contrast, TTX-s Na(+) channels in DRG cells and Na(+) channels in ventricular myocytes were found to have a much lower sensitivity to both GTX analogs. In single-channel recording on DRG cells and ventricular myocytes, Na(+) channels modified by the two GTX analogs (both at 100 microM), had similar relative conductances (range, 0.25-0.42) and open channel probabilities (range, 0.5-0.71). From these observations, we conclude that the differences in responsiveness of DRG TTX-i, and ventricular whole cell Na(+) currents to the GTX analogs studied are related to the number of Na(+) channels modified.

[IFOBT-positive gastric cancer].

Among 888 patients who underwent operation or endoscopic resection for gastric cancer (1994-1998), 75 patients, who had no colorectal disease or only small polyps 5 mm or less in diameter, were positive on the immunologic fecal occult blood test (IFOBT) (the positive group). They are compared with the other 813 patients (the negative group) as to the following 6 points: symptoms, presence of anemia, depth of invasion including macroscopic appearance, location, maximum diameter of lesions, and microscopic findings. The rate of positive-IFOBT gastric cancer was 8.4%. The average blood hemoglobin concentration was significantly lower in the positive group than in the negative group. Advanced cancers, especially type 2 and 3, were significantly more frequent in the positive group than in the negative group. The size of the lesions tended to be larger in the positive group than in the negative group. There was no difference between the groups as to symptoms, location, depth of invasion and microscopic findings. In conclusion, IFOBT-positive patients who have no colorectal disease or only small polyps 5 mm or less in diameter should be recommended to undergo upper gastrointestinal endoscopy.