Sepsis-Associated Delirium: A Narrative Review.

Delirium is characterized by an acutely altered mental status accompanied by reductions in cognitive function and attention. Delirium in septic patients, termed sepsis-associated delirium (SAD), differs in several specific aspects from the other types of delirium that are typically encountered in intensive care units. Since sepsis and delirium are both closely associated with increased morbidity and mortality, it is important to not only prevent but also promptly diagnose and treat SAD. We herein reviewed the etiology, pathogenesis, risk factors, prevention, diagnosis, treatment, and prognosis of SAD, including coronavirus disease 2019 (COVID-19)-related delirium. Delirium by itself not only worsens long-term prognosis, but it is also regarded as an important factor affecting the outcome of post-intensive care syndrome. In COVID-19 patients, the difficulties associated with adequately implementing the ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials: Choice of analgesia and sedation; Delirium assess, prevent, and manage; Early mobility and exercise; Family engagement/empowerment) and the need for social isolation are issues that require the development of conventional care for SAD.

Pharmacokinetics of Teicoplanin in a Patient with Coronavirus Disease 2019 Receiving Veno-venous Extracorporeal Membrane Oxygenation.

Introduction: Patients with severe coronavirus disease 2019 (COVID-19) receiving ventilation or pulmonary support via veno-venous extracorporeal membrane oxygenation (VV-ECMO) can be infected with drug-resistant bacteria. When introducing VV-ECMO, the changes in serum antibiotic concentration should be considered due to an increased volume of distribution (Vd). However, no pharmacokinetic study has assessed teicoplanin (TEIC) treatment in patients with COVID-19 receiving VV-ECMO. Case presentation: A 71-year-old man diagnosed with COVID-19 visited a primary hospital. His oxygenation conditions worsened despite treatment with favipiravir and methylprednisolone as well as oxygen therapy. After his transfer to our center, tracheal intubation and steroid pulse therapy were initiated. Seven days after admission, VV-ECMO was performed. TEIC was administered for secondary bacterial infection. The serum TEIC concentration remained within the therapeutic range, indicating that VV-ECMO did not significantly affect TEIC pharmacokinetics. VV-ECMO was discontinued 17 days after admission. However, he developed multi-organ disorder and died 42 days after admission. Conclusion: As TEIC prevents viral invasion, it may be used with ECMO in patients with COVID-19 requiring ventilation; however, the altered pharmacokinetics of TEIC, such as increased Vd, should be considered. Therefore, TEIC pharmacokinetics in VV-ECMO should be assessed in future studies with an appropriate number of patients.

The Visceral-to-subcutaneous Adipose Tissue Area Ratio Is Associated with Retreatment in Chronic Pancreatitis Patients with Pancreatolithiasis after Extracorporeal Shock Wave Lithotripsy.

Objective Extracorporeal shock wave lithotripsy (ESWL) has been used to treat pancreatolithiasis in patients with chronic pancreatitis (CP), but the high recurrence rate remains challenging. We therefore evaluated the association between body composition parameters and the prediction of retreatment after ESWL. Methods This study retrospectively evaluated 42 patients with CP who had been treated with ESWL between 2008 and 2019 in a single center. Body composition parameters were measured on pretreatment computed tomography images. Patients who underwent repeat ESWL were classified as the retreatment group. Results There were 13 (31.0%) and 29 (69.0%) patients in the retreatment and non-retreatment groups, respectively. The visceral-to-subcutaneous adipose tissue area ratio (VSR) of the retreatment group was significantly lower than that of the non-retreatment group (p=0.016). When divided by the median VSR, 10 of the 20 patients with a VSR of <0.85 underwent retreatment, whereas 3 of the 22 patients with a VSR of ≥0.85 underwent retreatment (p=0.019). According to a multivariate analysis, the VSR (p=0.010) and age (p=0.037) were independent factors associated with retreatment after ESWL. Conclusion This study showed that the VSR can predict the retreatment of patients with CP after ESWL.

Symbiotic polyamine metabolism regulates epithelial proliferation and macrophage differentiation in the colon.

Intestinal microbiota-derived metabolites have biological importance for the host. Polyamines, such as putrescine and spermidine, are produced by the intestinal microbiota and regulate multiple biological processes. Increased colonic luminal polyamines promote longevity in mice. However, no direct evidence has shown that microbial polyamines are incorporated into host cells to regulate cellular responses. Here, we show that microbial polyamines reinforce colonic epithelial proliferation and regulate macrophage differentiation. Colonisation by wild-type, but not polyamine biosynthesis-deficient, Escherichia coli in germ-free mice raises intracellular polyamine levels in colonocytes, accelerating epithelial renewal. Commensal bacterium-derived putrescine increases the abundance of anti-inflammatory macrophages in the colon. The bacterial polyamines ameliorate symptoms of dextran sulfate sodium-induced colitis in mice. These effects mainly result from enhanced hypusination of eukaryotic initiation translation factor. We conclude that bacterial putrescine functions as a substrate for symbiotic metabolism and is further absorbed and metabolised by the host, thus helping maintain mucosal homoeostasis in the intestine.

Polyamines polarized Th2/Th9 cell-fate decision by regulating GATA3 expression.

Polyamines produced by both prokaryotes and eukaryotes are bioactive substances with pleiotropic effects. Accumulating evidence has demonstrated that polyamines contribute to anti-inflammatory responses by suppressing the expression of proinflammatory cytokines in mononuclear cells and macrophages. However, the effects of polyamines on CD4+ T cell responses remain to be elucidated. Here, we investigated the effect of polyamines on cell fate decisions of naïve CD4+ T cells in vitro. We found that endogenously generated polyamines are essential for the development of T helper 2 (Th2) cells. Treatment with DL-2-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, diminished GATA3 expression in CD4+ T cells under Th2-skewed conditions. Supplementation of exogenous polyamines rescued GATA3 downregulation caused by DFMO treatment in CD4+ T cells. Transcriptome analysis revealed that deprivation of endogenous polyamines resulted in upregulated Th9-related genes, such as Il9, Irf4, and Batf3, even under the Th2-skewing conditions. Depletion of intracellular polyamines reduced GATA3 expression but increased IL-9-producing CD4+ T cells under both Th2 and Th9-skewing conditions. Furthermore, oral administration of DFMO increased IL-9-producing CD4+ T cells in small intestine in mice. Thus, our data indicate that polyamines play a critical role in the regulation of the Th2/Th9 balance.

Microbiota-derived butyrate limits the autoimmune response by promoting the differentiation of follicular regulatory T cells.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder with a high prevalence, especially in industrialized countries. Dysbiosis of the intestinal microbiota has been observed in RA patients. For instance, new-onset untreated RA (NORA) is associated with the underrepresentation of the Clostridium cluster XIVa, including Lachnospiraceae, which are major butyrate producers, although the pathological relevance has remained obscure. Follicular regulatory T (TFR) cells play critical regulatory roles in the pathogenesis of autoimmune diseases, including RA. Reduced number of circulating TFR cells has been associated with the elevation of autoantibodies and disease severity in RA. However, the contribution of commensal microbe-derived butyrate in controlling TFR cell differentiation remains unknown. METHODS: We examined the contribution of microbe-derived butyrate in controlling autoimmune arthritis using collagen-induced arthritis (CIA) and SKG arthritis models. We phenotyped autoimmune responses in the gut-associated lymphoid tissues (GALT) in the colon and joint-draining lymph nodes in the CIA model. We developed an in vitro CXCR5+Bcl-6+Foxp3+ TFR (iTFR) cell culture system and examined whether butyrate promotes the differentiation of iTFR cells. FINDINGS: Microbe-derived butyrate suppressed the development of autoimmune arthritis. The immunization of type II collagen (CII) caused hypertrophy of the GALT in the colon by amplifying the GC reaction prior to the onset of the CIA. Butyrate mitigated these pathological events by promoting TFR cell differentiation. Butyrate directly induced the differentiation of functional TFR cells in vitro by enhancing histone acetylation in TFR cell marker genes. This effect was attributed to histone deacetylase (HDAC) inhibition by butyrate, leading to histone hyperacetylation in the promoter region of the TFR-cell marker genes. The adoptive transfer of the butyrate-treated iTFR cells reduced CII-specific autoantibody production and thus ameliorated the symptoms of arthritis. INTERPRETATION: Accordingly, microbiota-derived butyrate serves as an environmental cue to enhance TFR cells, which suppress autoantibody production in the systemic lymphoid tissue, eventually ameliorating RA. Our findings provide mechanistic insights into the link between the gut environment and RA risk. FUNDING: This work was supported by AMED-Crest (16gm1010004h0101, 17gm1010004h0102, 18gm1010004h0103, and 19gm1010004s0104 to KH), the Japan Society for the Promotion of Science (JP17KT0055, JP16H01369, and JP18H04680 to KH; JP17K15734 to DT), Keio University Special Grant-in-Aid for Innovative Collaborative Research Projects (KH), Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research (DT), the SECOM Science and Technology Foundation (KH), the Cell Science Research Foundation (KH), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (DT), the Suzuken Memorial Foundation (KH and DT), the Takeda Science Foundation (KH and DT), The Science Research Promotion Fund, and The Promotion and Mutual Aid Corporation for Private Schools of Japan (KH).

Rare gastric outlet obstruction owing to ectopic pancreas: a case report and literature review.

The ectopic pancreas is often observed in the gastrointestinal tract, and is typically asymptomatic. A 28-year-old woman was referred to our hospital following repeated vomiting after every meal. Following gastroscopy, contrast-enhanced computed tomography (CE-CT), and endoscopic ultrasonography (EUS), she was diagnosed with gastric outlet obstruction, also known as pyloric obstruction, caused by a giant submucosal cystic tumor. The condition was successfully treated with EUS-guided cystic drainage, and she was diagnosed with a cystic tumor originating from the ectopic pancreas. The tumor shrank following EUS-guided cystic drainage, and her obstructive symptoms resolved. In cases with overgrowth of the ectopic pancreas, the differential diagnosis of malignancy is important but challenging. Herein, we report a unique final pathology of this rare case and discuss the findings with a literature review.

Early-stage T1b adenocarcinoma arising in the remnant cystic duct after laparoscopic cholecystectomy: a case report and literature review.

BACKGROUND: The cystic duct has been included in the staging classification scheme for gallbladder cancer since the 2010 publication of the AJCC Cancer Staging Manual (7th edition). To our knowledge, only seven other cases of adenocarcinoma arising in the remnant cystic duct following cholecystectomy have been reported in the English-language literature, and none has been reported as primary early-stage T1b remnant cystic duct cancer (CDC). We report, herein, a case of primary adenocarcinoma arising in the remnant cystic duct in a patient with history of laparoscopic cholecystectomy for gallstone disease. CASE PRESENTATION: An 81-year-old female presented with abdominal pain. Her medical history included a laparoscopic cholecystectomy for cholecystolithiasis two years prior. Jaundice was observed; imaging studies suggested that this was caused by choledocholithiasis. Blood chemistry findings showed severe liver dysfunction. Endoscopic retrograde cholangiography revealed haemobilia from the common bile duct with no evidence of choledocholithiasis. A bile sample showed Papanicolaou class IV cytology. As the extent of tumour spread was undetermined by abdominal ultrasonography and endoscopic ultrasonography, peroral cholangioscopy (POCS) was performed, which revealed tiny papillary lesions within the confluence of cystic duct, and fine granular lesions in the centre of bile ducts, signifying early-stage remnant CDC. Extrahepatic bile duct resection with regional lymphadenectomy was done. Histopathological findings revealed a 42-mm tubular adenocarcinoma originating from the remnant cystic duct with the considerable shallow spread across the extrahepatic bile ducts. It invaded the fibromuscular layer, with no lymphovascular or perineural invasion, no lymph node metastasis (13 nodes examined), and uninvolved surgical resection margin (R0 resection), and was staged as pT1bN0M0, Stage I. CONCLUSIONS: Primary early-stage T1b remnant CDC is an uncommon condition for which early diagnosis is challenging; if intraoperatively recognized, it can complicate surgery. Our experience of this case and an overview of the English literature suggest that POCS is an efficient tool to diagnosis this tumour and assess its spread along the extrahepatic bile ducts.

Influenza A with hemorrhagic shock and encephalopathy syndrome in an adult: A case report.

INTRODUCTION: Hemorrhagic shock and encephalopathy syndrome (HSES) is a type of acute encephalopathy mainly seen in infants. It is a syndrome encompassing an onset of high fever, disturbance of consciousness, convulsion, and shock that rapidly progresses to watery diarrhea and liver and renal dysfunctions. It is extremely rare in adults, and the number of reports is limited worldwide. We report the case of an adult patient with HSES, which occurred after influenza A infection. PATIENT CONCERNS: A 52-year-old man visited his family doctor 2 days after he noticed fever and was diagnosed with influenza A using an influenza rapid diagnosis kit; he underwent treatment on an outpatient basis. He was immediately hospitalized after developing fever, abdominal pain, malaise, and shock 16 hours after the commencement of the treatment. Abrupt acute brain swelling was noted 24 hours after hospitalization. DIAGNOSES: The antibody titer to influenza A (H3N2) was 1:40. Computed tomography obtained 24 hours after treatment initiation confirmed acute cerebral edema and cerebral herniation. Electroencephalogram at that time showed a flat line. INTERVENTIONS: For the treatment of influenza A, laninamivir 150 mg was started immediately after the diagnosis by the family doctor, and 600 mg dose was given daily after hospitalization (or since 24 hours after the treatment initiation). For the management of shock, dobutamine 3 µg/kg/min and noradrenaline up to 0.2 µg/kg/min were used together with bolus infusion. OUTCOMES: The patient was declared brain dead on his 6th hospital day and he died on his 27th hospital day. CONCLUSION: Drastic courses such as that in our case with HSES can follow influenza infections even in adults.

Intestinal luminal putrescine is produced by collective biosynthetic pathways of the commensal microbiome.

The intestinal microbiome produces various metabolites that may harm or benefit the host. However, the production pathways of these metabolites have not been well characterised. The polyamines putrescine and spermidine required for physiological process are also produced by intestinal microbiome. The production and release of these polyamines by microbiome are poorly understood, though we have confirmed that intestinal bacteria produced putrescine from arginine. In this study, we characterised polyamine synthesis by analysing the collective metabolic functions of the intestinal microbiome. In particular, we analysed polyamines and their intermediates in faecal cultures, as well as the colonic contents of rats injected with isotope-labelled arginine through a colon catheter, using mass spectrometry. Isotope-labelled putrescine was detected in faecal cultures and colonic contents of rats injected with isotope-labelled arginine. Putrescine is produced through multiple pathways, and its extracellular intermediates are exchanged between bacterial species. Additionally, we demonstrated that the collective metabolic pathway depends on a complex exchange of metabolites released into the colonic lumen. This study demonstrates the existence of putrescine biosynthetic pathways based on the collective metabolic functions of the intestinal microbial community. Our findings provide knowledge to manipulate the levels of intestinal microbial products, including polyamines, that may modulate host health.

Long-Term Outcomes of Pancreatic Function Following Pancreatic Trauma.

The objective of this study is to retrospectively assess long-term outcomes and late complications of pancreatic trauma. We studied 14 patients with pancreatic trauma who were treated at the Advanced Emergency Medical Service Center, Kurume University Hospital, between 1981 and 2012 and discharged alive. Relevant data were extracted from patient records and a retrospective patient questionnaire and blood test were completed to evaluate pancreatic function. The median patient age at the time of the survey was 49 years; the median post-injury period was 23 years and 5 months. The comorbidity rates for pancreatic endocrine and exocrine dysfunctions were 35.7% and 33.3%, respectively. No new-onset diabetes mellitus (DM) was seen within 3 years of trauma, except in 1 patient who underwent pancreaticoduodenectomy. DM developed >15 years after trauma in 2 patients each in the pancreatectomy and non-pancreatectomy groups. Diarrhea exacerbated by fat intake was seen in 3 and 1 patient in the pancreatectomy and non-pancreatectomy groups, respectively. Both complications were more common in the pancreatectomy group, but without statistical significance. Although post-surgical pancreatic dysfunction may be absent at discharge, treatment for pancreatic trauma should take into account the possibility that pancreatectomy may accelerate DM onset.

A Novel Putrescine Exporter SapBCDF of Escherichia coli.

Recent research has suggested that polyamines (putrescine, spermidine, and spermine) in the intestinal tract impact the health of animals either negatively or positively. The concentration of polyamines in the intestinal tract results from the balance of uptake and export of the intestinal bacteria. However, the mechanism of polyamine export from bacterial cells to the intestinal lumen is still unclear. In Escherichia coli, PotE was previously identified as a transporter responsible for putrescine excretion in an acidic growth environment. We observed putrescine concentration in the culture supernatant was increased from 0 to 50 µm during growth of E. coli under neutral conditions. Screening for the unidentified putrescine exporter was performed using a gene knock-out collection of E. coli, and deletion of sapBCDF significantly decreased putrescine levels in the culture supernatant. Complementation of the deletion mutant with the sapBCDF genes restored putrescine levels in the culture supernatant. Additionally, the ΔsapBCDF strain did not facilitate uptake of putrescine from the culture supernatant. Quantification of stable isotope-labeled putrescine derived from stable isotope-labeled arginine supplemented in the medium revealed that SapBCDF exported putrescine from E. coli cells to the culture supernatant. It was previously reported that SapABCDF of Salmonella enterica sv. typhimurium and Haemophilus influenzae conferred resistance toantimicrobial peptides; however, the E. coli ΔsapBCDF strain did not affect resistance to antimicrobial peptide LL-37. These results strongly suggest that the natural function of the SapBCDF proteins is the export of putrescine.

Development of a teicoplanin loading regimen that rapidly achieves target serum concentrations in critically ill patients with severe infections.

We performed high-dose loading (12 mg/kg every 12 h for 48 h; 4 doses total) of teicoplanin (TEIC) in patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infections, with the goal of achieving target serum concentration (TEICc) ≥ 15 mg/l within 48 h of starting administration. The safety and effectiveness of the fixed, early-stage administration method were evaluated across a range of kidney dysfunction severity levels. TEIC high-dose loading was administered to 106 patients with MRSA infection from February 2010 to February 2013. After high-dose loading, maintenance doses based on therapeutic drug monitoring (TDM) of TEICc were administered via 30-min intravenous drips, every 24 h. Subjects were divided into 4 groups based on kidney function and renal replacement therapy (RRT) status for safety and effectiveness evaluation: group 1 (G1) did not undergo RRT and exhibited creatinine clearance (Ccr; ml/min/m(2)) >50, group 2 (G2) exhibited Ccr ≤ 50, group 3 (G3) underwent continuous RRT (CRRT), and group 4 (G4) underwent intermittent RRT (IRRT). TEICc was measured after 24, 48, 72, and 144 h, immediately before TEIC administration. Target TEICc was reached in all groups, and bacteriological effectiveness and utility were high in G1, G2, and G3. The maximum TEICc (≥ 28.0 mg/l) and serum albumin (≤ 1.84 g/dl) were associated with organ toxicity. Fixed high-dose loading of TEIC achieved the target therapeutic range (≥ 15 mg/l) within 48 h of the start of administration regardless of kidney dysfunction, and exhibited sufficient utility.

Antipruritic effects of the probiotic strain LKM512 in adults with atopic dermatitis.

BACKGROUND: Evidence suggests that intestinal microbiota play an important role in the pathogenesis of atopic dermatitis (AD) through induction of immunosuppression and immune tolerance; however, the exact underlying mechanism is unclear. Few studies to date have examined the effects of probiotics on adult-type AD. OBJECTIVE: To examine the effects of the probiotic Bifidobacterium animalis subsp lactis LKM512 on adult-type AD and the expression of metabolites that are known to be influenced by gut microbiota in fecal samples. METHODS: Forty-four patients were randomly assigned to receive LKM512 or a placebo and underwent medical examinations. Fecal microbiota were analyzed with real-time polymerase chain reaction. Metabolomic analysis was conducted to search for antipruritic metabolites produced by intestinal bacteria using feces derived from 3 patients whose itch scores had improved using capillary electrophoresis with time-of-flight mass spectrometry. Antipruritic effects of kynurenic acid were observed using AD-induced NC/Nga mice. RESULTS: LKM512 administration alleviated itch in AD patients compared with controls and improved the dermatology-specific quality-of-life scores when compared with the controls. Administration of LKM512 also increased the expression of the antipruritic and antinociceptive metabolite kynurenic acid (KYNA) in patients whose itch score had improved after LKM512 treatment. In mouse experiments, scratching behavior counts tended to be decreased by KYNA injection when compared with no treatment. CONCLUSION: LKM512 administration may exert antipruritic effects by increasing KYNA production. LKM512 could therefore be a potentially effective therapeutic candidate for the reduction of pruritus. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000005695.

Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice.

Prevention of quality of life (QOL) deterioration is associated with the inhibition of geriatric diseases and the regulation of brain function. However, no substance is known that prevents the aging of both body and brain. It is known that polyamine concentrations in somatic tissues (including the brain) decrease with increasing age, and polyamine-rich foods enhance longevity in yeast, worms, flies, and mice, and protect flies from age-induced memory impairment. A main source of exogenous polyamines is the intestinal lumen, where they are produced by intestinal bacteria. We found that arginine intake increased the concentration of putrescine in the colon and increased levels of spermidine and spermine in the blood. Mice orally administered with arginine in combination with the probiotic bifidobacteria LKM512 long-term showed suppressed inflammation, improved longevity, and protection from age-induced memory impairment. This study shows that intake of arginine and LKM512 may prevent aging-dependent declines in QOL via the upregulation of polyamines.

Prediction of Helicobacter pylori status by conventional endoscopy, narrow-band imaging magnifying endoscopy in stomach after endoscopic resection of gastric cancer.

BACKGROUND: To reduce the incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer, Helicobacter pylori eradication therapy has been endorsed. It is not unusual for such patients to be H. pylori negative after eradication or for other reasons. If it were possible to predict H. pylori status using endoscopy alone, it would be very useful in clinical practice. To clarify the accuracy of endoscopic judgment of H. pylori status, we evaluated it in the stomach after endoscopic submucosal dissection (ESD) of gastric cancer. MATERIALS AND METHODS: Fifty-six patients treated by ESD were enrolled. The diagnostic criteria for H. pylori status by conventional endoscopy and narrow-band imaging (NBI)-magnifying endoscopy were decided, and H. pylori status was judged by two endoscopists. Based on the H. pylori stool antigen test as a diagnostic gold standard, conventional endoscopy and NBI-magnifying endoscopy were compared for their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Interobserver agreement was assessed in terms of κ value. RESULTS: Interobserver agreement was moderate (0.56) for conventional endoscopy and substantial (0.77) for NBI-magnifying endoscopy. The sensitivity, specificity, PPV, and NPV were 0.79, 0.52, 0.70, and 0.63 for conventional endoscopy and 0.91, 0.83, 0.88, and 0.86 for NBI-magnifying endoscopy, respectively. CONCLUSIONS: Prediction of H. pylori status using NBI-magnifying endoscopy is practical, and interobserver agreement is substantial.

Prediction of submucosal gastric cancer by narrow-band imaging magnifying endoscopy.

BACKGROUND: The features of gastric submucosal cancer revealed by magnifying endoscopy have not been reported. Aim of our study was to investigate whether magnifying endoscopy could contribute to the diagnosis of submucosal invasion. PATIENTS AND METHODS: In this prospective, cross-sectional study, 197 lesions of gastric differentiated adenocarcinoma, diagnosed as mucosal cancer by conventional endoscopy, were observed by magnifying endoscopy with narrow-band imaging, paying attention to the presence of a blurry mucosal pattern and an irregular mesh pattern. After endoscopic submucosal dissection, all lesions were examined histologically and the areas of two features were estimated. RESULTS: Among the lesions examined, 177 were diagnosed histologically as mucosal cancer and 20 as submucosal cancer. Multivariate logistic regression analysis confirmed that a blurry mucosal pattern (odds ratio 12.15, 95% confidence interval 3.45-42.76, p=0.000) and an irregular mesh pattern (22.55, 4.22-120.45, p=0.000) were independent predictors of submucosal invasion. CONCLUSIONS: Narrow band imaging magnifying endoscopic features are useful for predicting submucosal invasion in gastric cancer.

Diagnosis of Early Gastric Cancer by Magnifying Endoscopy with NBI from Viewpoint of Histological Imaging: Mucosal Patterning in terms of White Zone Visibility and Its Relationship to Histology.

THE DIAGNOSIS OF EARLY GASTRIC CANCER BY MAGNIFYING ENDOSCOPY WITH NBI IS BASED ON TWO COMPONENTS: microvascular pattern and mucosal pattern. Mucosal patterns are characterized by a whitish edge, which has been named the white zone. Some cancerous areas showing a distinct white zone form clear mucosal patterns, whereas others showing a nondistinct white zone do not form mucosal patterns. The aim of the present study was to clarify the histological differences between these two types of area. In transverse sections of gastric epithelium, the lengths of intervening parts in areas showing a distinct white zone, a nondistinct white zone, and an invisible white zone were measured, and the depths of the crypts in these three types of area were also measured. The intervening parts in areas with a nondistinct or invisible white zone were shorter than those in areas with a distinct white zone (P < 0.05), and the crypts in the former areas were shallower than those in the latter (P < 0.01). Areas in which the intervening part were long and the crypts deep tended to show a distinct white zone, whereas areas with short intervening parts or shallow crypts tended to show a nondistinct or non-visible white zone.