Cancer gland rupture as a potential risk factor for lymph node metastasis in early colorectal adenocarcinoma with deep submucosal invasion.

AIMS: Lymph node metastasis (LNM) has not been found in more than 85% of patients with early invasive colorectal adenocarcinoma (T1-CRAC) who undergo surgery after therapeutic endoscopy due to the risk for LNM. Better histological risk assessment for LNM of endoscopically resected T1-CRAC is important to avoid unnecessary additional surgery. METHODS AND RESULTS: We evaluated cancer gland rupture (CGR), i.e. cancer glands with a discontinuous epithelial lining, at the invasive front, as a potential risk factor for LNM by histological examination of differentiated T1-CRAC from 217 patients who underwent surgery with or without therapeutic endoscopy. CGR was represented by C-shaped neoplastic glands with a variable inflammatory or stromal reaction, and was occasionally accompanied by mucus lake or abscess formation. CGR was observed in 168 (77%) cases, including all 20 cases with LNM, and the odds ratio of LNM was higher for CGR than for deep invasion (depth of submucosal invasion ≥1000 µm). All cases with LNM were found among 148 cases with deep invasion and positive CGR, whereas no LNM was detected in 29 cases with deep invasion and negative CGR, regardless of vascular invasion or tumour budding. In the 148 cases, LNM was detected in 18 (19%) of 93 cases with positive vascular invasion or high-grade tumour budding, and in two (4%) of 55 cases without either. CONCLUSIONS: Our findings suggest that CGR is an easily applied and objective histological finding for predicting LNM that could be useful for assessing the risk for LNM of endoscopically resected T1-CRAC with deep invasion.

A Novel CNN-Based Framework for Classification of Signal Quality and Sleep Position from a Capacitive ECG Measurement.

The further exploration of the capacitive ECG (cECG) is hindered by frequent fluctuations in signal quality from body movement and changes in sleep position. The processing framework must be fundamentally adapted to make full use of this signal. Therefore, we propose a new signal-processing framework that determines the signal quality for short signal segments (2 and 4 seconds) using a multi-class classification model (qua_model) based on a convolutional neural network (CNN). We built another independent deep CNN classifier (pos_model) to classify the sleep position. In the validation, 12 subjects were recruited for a 30-minute experiment, which required the subjects to lie on a bed in different sleeping positions. The short segments, classified as clear (C1 class) by the qua_model, were used to determine sleep positions with the pos_model. In 10-fold cross-validation, the qua_model for signals of 4-second length could recognize the signal of the C1 class at a 0.99 precision and a 0.99 recall; the pos_model could recognize the supine sleep position, the left, and right lateral sleep positions at a 0.99 averaged precision and a 0.99 averaged recall. Given the amount of data accumulated per night and the instability in the signal quality, this fully automatic processing framework is indispensable for a personal healthcare system. Therefore, this study could serve as an important step for cECG technique trying to explore the cECG for unconstrained heart monitoring.

Estimation of Gait Independence Using a Tri-Axial Accelerometer in Stroke Patients.

The purpose of this study was to clarify whether a gait analysis using an accelerometer could estimate gait independence. Eighty-six stroke patients and 21 healthy control subjects participated in this study. Stroke patients were identified as dependent or independent based on their gait ability. The acceleration of the trunk and bilateral thigh was measured using three wireless sensors during walking. The root mean square, gait regularity, and symmetry were calculated from the acceleration to estimate gait quality. ANCOVA showed that gait regularity of the trunk and bilateral thigh were significantly lowest in the dependent group, regardless of gait velocity. A logistic regression analysis showed that the regularity and root mean square of the anteroposterior acceleration of the unaffected thigh were the key factors for estimating gait independence. This study suggests that an acceleration-based gait analysis facilities gait independence estimation, and is a useful tool during the rehabilitation of stroke patients.

"Crawling-type" adenocarcinoma of the stomach: a distinct entity preceding poorly differentiated adenocarcinoma.

BACKGROUND: Gastric "crawling-type" adenocarcinoma (CTAC) is a neoplasm histologically comprising irregularly fused glands with low-grade cellular atypia that tends to spread laterally in the mucosa. It is necessary to elucidate the clinicopathological characteristics of CTAC. METHODS: We evaluated 25 CTACs-16 intramucosal (M-) and 9 submucosal invasive (SM-) cancers-clinicopathologically and immunohistochemically. RESULTS: CTAC was most frequently located in the lesser curvature of the middle-third of the stomach. Macroscopically, 21 lesions were superficial-depressed and 4 were superficial-flat type. Histologically, all CTACs had cystic dilated glands and 16 lesions had focal signet-ring cells. All invasive areas of the SM-CTACs were occupied by poorly differentiated adenocarcinoma with an infiltrative growth pattern and abundant stroma. Fifteen CTACs were surrounded by mucosa with partial or no intestinal metaplasia. In the intramucosal area, 24 lesions were mixed phenotype with mucin and brush border immunoexpression. SM-CTAC was frequent in lesions with an intramucosal poorly differentiated component (PDC) greater than 10 mm in size (P = 0.041), and lymph node metastasis (LNM) was frequent in lesions with a PDC greater than 20 mm (P = 0.039). The frequency of an expanded pattern (Ki-67-positive cells occupying > 50 % of the mucosa) was higher in SM-CTAC than in M-CTAC (P = 0.027). p53 overexpression was not detected in the intramucosal areas of any of the lesions. CONCLUSION: CTAC is a distinct subgroup of gastric adenocarcinoma in the early phase. A larger PDC and a Ki-67 expanded pattern were predictive of submucosal invasion or LNM.

A gait abnormality measure based on root mean square of trunk acceleration.

BACKGROUND: Root mean square (RMS) of trunk acceleration is seen frequently in gait analysis research. However, many studies have reported that the RMS value was related to walking speed. Therefore, the relationship between the RMS value and walking speed should be considered when the RMS value is used to assess gait abnormality. We hypothesized that the RMS values in three sensing axes exhibit common proportions for healthy people if they walk at their own preferred speed and that the RMS proportions in abnormal gait deviate from the common proportions. In this study, we proposed the RMS ratio (RMSR) as a gait abnormality measure and verified its ability to discriminate abnormal gait. METHODS: Forty-seven healthy male subjects (24-49 years) were recruited to examine the relationship between walking speed and the RMSR. To verify its ability to discriminate abnormal gait, twenty age-matched male hemiplegic patients (30-48 years) participated as typical subjects with gait abnormality. A tri-axial accelerometer was attached to their lower back, and they walked along a corridor at their own preferred speed. We defined the RMSR as the ratio between RMS in each direction and the RMS vector magnitude. RESULTS: In the healthy subjects, the RMS in all directions related to preferred walking speed. In contrast, RMSR in the mediolateral (ML) direction did not correlate with preferred walking speed (rs = -0.10, p = 0.54) and represented the similar value among the healthy subjects. Moreover, the RMSR in the ML direction for the hemiplegic patients was significantly higher than that for the healthy subjects (p < 0.01). CONCLUSIONS: These results suggest that the RMSR in the ML direction exhibits a common value when healthy subjects walk at their own preferred speed, even if their preferred walking speed were different. For subjects with gait abnormality, the RMSR in the ML direction deviates from the common value of healthy subjects. The RMSR in the ML direction may potentially be a quantitative measure of gait abnormality.

Synergistic tumour suppressor activity of E-cadherin and p53 in a conditional mouse model for metastatic diffuse-type gastric cancer.

BACKGROUND: Gastric cancer is the second most frequent cause of death from cancer in the world, diffuse-type gastric cancer (DGC) exhibiting a poor prognosis. Germline mutations of CDH1, encoding E-cadherin, have been reported in hereditary DGC, and genetic and/or epigenetic alterations of CDH1 are frequently detected in sporadic DGC. Genetic alterations of TP53 are also frequently found in DGC. To examine the synergistic effect of the loss of E-cadherin and p53 on gastric carcinogenesis, a mouse line was established in which E-cadherin and p53 are specifically inactivated in the stomach parietal cell lineage. METHODS: Atp4b-Cre mice were crossed with Cdh1(loxP/loxP) and Trp53(loxP/loxP) mice, and the gastric phenotype of Atp4b-Cre(+);Cdh1(loxP/loxP);Trp53(loxP/loxP) double conditional knockout (DCKO) mice was examined. RESULTS: Non-polarised E-cadherin-negative parietal cells and proton pump-negative atypical foci were observed in DCKO mice. Intramucosal cancers and invasive cancers composed of poorly differentiated carcinoma cells and signet ring cells, histologically very similar to those in humans, were found from 6 to 9 months, respectively. Fatal DGC developed at 100% penetrance within a year, frequently metastasised to lymph nodes, and had tumourigenic activity in immunodeficient mice. Gene expression profiles of DGC in DCKO mice also resembled those of human DGC, and mesenchymal markers and epithelial-mesenchymal transition-related genes were highly expressed in mouse DGC as in human DGC. CONCLUSION: This mouse line is the first genetically engineered mouse model of DGC and is very useful for clarifying the mechanism underlying gastric carcinogenesis, and provides a new approach to the treatment and prevention of DGC.

Selective Inhibition of L-type Amino Acid Transporter 1 Suppresses Cell Proliferation in Ovarian Clear Cell Carcinoma.

BACKGROUND/AIM: Ovarian clear cell carcinoma (OCCC) is a histological type of ovarian cancer that is refractory to chemotherapy and has poor prognosis, which necessitates the development of novel treatment therapies. In this study, we focused on L-type amino acid transporter 1 (LAT1), which is involved in cancer growth, and investigated the effect of its selective inhibition on cell proliferation in OCCC. MATERIALS AND METHODS: The inhibitory effect of nanvuranlat (JPH203), a LAT1 selective inhibitor, on the cellular uptake of [3H] leucine was evaluated using the OCCC cell line JHOC9, which expresses the LAT1 protein. In addition, the kinetics of cell proliferation and changes in phosphorylation of the mTOR pathway were analyzed. The correlation between LAT1 expression and progression-free survival (PFS) was evaluated using clinical specimens of OCCC. RESULTS: Nanvuranlat inhibited [3H] leucine intracellular uptake and cell proliferation in a dose-dependent manner in JHOC9 cells. In addition, it suppressed the activity of the mTOR signaling pathway, which is thought to inhibit cancer cell proliferation. LAT1 expression was most frequent in OCCC among clinical specimens of epithelial ovarian cancer. A correlation between LAT1 expression and PFS was observed in OCCC. CONCLUSION: LAT1 selective inhibition suppresses cell proliferation via the mTOR pathway by inhibiting leucine uptake in OCCC. This study illustrates the potential of using LAT1 selective inhibition as a treatment strategy for OCCC.

The role of cyclobutenes in gold(I)-catalysed skeletal rearrangement of 1,6-enynes.

1,6-Enynes with electron-donating substituents at the alkyne undergo gold(I)-catalysed single cleavage skeletal rearrangement, whereas substrates with electron-withdrawing substituents evolve selectively to double cleavage rearrangement. Theoretical calculations provide a qualitative rationale for these effects, and suggest that bicyclo[3.2.0]hept-5-enes are involved as intermediates. We provide the first X-ray structural evidence for the formation of a product of this class in a cycloisomerisation of a 1,6-enyne.

[Immunohistochemical detection of Helicobacter pylori with a novel monoclonal antibody: Its clinicopathological significance and validity in the routine pathological diagnosis].

The immunological mechanism of Helicobacter pylori-induced chronic gastritis is still unknown. In our previous study using a novel anti-H. pylori monoclonal antibody and surgically resected stomachs from gastric cancer patients, we succeeded to detect H. pylori captured by macrophages in gastric lamina propria and lymph nodes, and proved that the H. pylori-positive macrophages correlated with chronic gastritis. To elucidate this correlation in the cases without gastric cancer, we examined H. pylori in 519 gastric biopsy specimens of 242 cases using immunohistochemistry with the novel antibody. Also, we evaluated the validity of the novel antibody in the routine pathological diagnosis. In 402 specimens from the cases without gastric tumors, the bacteria were detected not only in the mucous layer of 148 specimens but also in the lamina propria of 144 specimens. The specimens only with the intramucosal bacteria showed high-grade chronic and low-grade acute inflammation, whereas the specimens only with the intra-mucous bacteria tended to show the low-grade chronic and high-grade acute inflammation. Statistically, H. pylori in the lamina propria correlated with chronic gastritis. When compared to commercially available anti-H. pylori antibody and Giemsa staining, the novel antibody showed the highest sensitivity to detect the bacteria in the lamina propria. These results suggest that H. pylori in the lamina propria is thought to be deeply related with the development of H. pylori-induced chronic gastritis also in the cases without gastric cancer. And, the novel antibody is proved to be very useful in the routine pathological assessment of H. pylori infection.

Radiomic Analysis for Pretreatment Prediction of Recurrence Post-Radiotherapy in Cervical Squamous Cell Carcinoma Cancer.

BACKGROUND: The current study aims to predict the recurrence of cervical cancer patients treated with radiotherapy from radiomics features on pretreatment T1- and T2-weighted MR images. METHODS: A total of 89 patients were split into model training (63 patients) and model testing (26 patients). The predictors of recurrence were selected using the least absolute shrinkage and selection operator (LASSO) regression. The machine learning used neural network classifiers. RESULTS: Using LASSO analysis of radiomics, we found 25 features from the T1-weighted and 4 features from T2-weighted MR images, respectively. The accuracy was highest with the combination of T1- and T2-weighted MR images. The model performances with T1- or T2-weighted MR images were 86.4% or 89.4% accuracy, 74.9% or 38.1% sensitivity, 81.8% or 72.2% specificity, and 0.89 or 0.69 of the area under the curve (AUC). The model performance with the combination of T1- and T2-weighted MR images was 93.1% accuracy, 81.6% sensitivity, 88.7% specificity, and 0.94 of AUC. CONCLUSIONS: The radiomics analysis with T1- and T2-weighted MR images could highly predict the recurrence of cervix cancer after radiotherapy. The variation of the distribution and the difference in the pixel number at the peripheral and the center were important predictors.

Immunohistochemical Differentiation between Western and East Asian Types of CagA-Positive Helicobacter pylori in Gastric Biopsy Samples.

Background: Cag A-positive Helicobacter pylori isolated from human gastric mucosa is categorized as a Western or East Asian allele-type based on whether the cagA gene encodes an EPIYA-C or EPIYA-D motif. We aimed to differentiate between the 2 types of H. pylori by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded (FFPE) gastric biopsy samples. Materials and Methods: We developed 2 monoclonal antibodies (mAbs) that detect either the EPIYA-C or EPIYA-D motif of the H. pylori CagA protein by IHC using FFPE tissues. FFPE tissue sections from 30 Japanese and 39 Brazilian gastric biopsy samples with H. pylori infection confirmed by Giemsa staining (moderate/severe in the Sydney classification system) were examined by IHC with the novel mAbs followed by polymerase chain reaction (PCR) for EPIYA-C or EPIYA-D using DNA extracted from adjacent tissue sections. Results: Differentiation among Western and East Asian types and CagA-negative H. pylori was successful in most (97%) samples by IHC with the novel mAbs and commercially available mAbs that react with a species-specific lipopolysaccharide or a common CagA motif of H. pylori. The detection status of EPIYA-C/D motifs by IHC with the novel mAbs was consistent with the PCR results in 61 (88%) of 69 samples: EPIYA-C(+)/D(-) in zero Japanese and 26 Brazilian samples, EPIYA-C(-)/D(+) in 26 Japanese and 1 Brazilian sample, and EPIYA-C(-)/D(-) in 1 Japanese and 7 Brazilian samples. The detection sensitivity and specificity of IHC with each novel mAb compared with the PCR results were, respectively, 84% and 97% for EPIYA-C, and 97% and 95% for EPIYA-D. Conclusions: The novel mAbs specific to each EPIYA-C or EPIYA-D motif differentiated between Western and East Asian types of CagA-positive H. pylori by IHC using FFPE tissues. Applying these novel mAbs to large numbers of archived pathology samples will contribute to elucidating the association of these allele types with gastric cancer.

Detection of anticipatory postural adjustments prior to gait initiation using inertial wearable sensors.

BACKGROUND: The present study was performed to evaluate and characterize the potential of accelerometers and angular velocity sensors to detect and assess anticipatory postural adjustments (APAs) generated by the first step at the beginning of the gait. This paper proposes an algorithm to automatically detect certain parameters of APAs using only inertial sensors. METHODS: Ten young healthy subjects participated in this study. The subjects wore an inertial unit containing a triaxial accelerometer and a triaxial angular velocity sensor attached to the lower back and one footswitch on the dominant leg to detect the beginning of the step. The subjects were standing upright on a stabilometer to detect the center of pressure displacement (CoP) generated by the anticipatory adjustments. The subjects were asked to take a step forward at their own speed and stride length. The duration and amplitude of the APAs detected by the accelerometer and angular velocity sensors were measured and compared with the results obtained from the stabilometer. The different phases of gait initiation were identified and compared using inertial sensors. RESULTS: The APAs were detected by all of the sensors. Angular velocity sensors proved to be adequate to detect the beginning of the step in a manner similar to the footswitch by using a simple algorithm, which is easy to implement in low computational power devices. The amplitude and duration of APAs detected using only inertial sensors were similar to those detected by the stabilometer. An automatic algorithm to detect APA duration using triaxial inertial sensors was proposed. CONCLUSIONS: These results suggest that the feasibility of accelerometers is improved through the use of angular velocity sensors, which can be used to automatically detect and evaluate APAs. The results presented can be used to develop portable sensors that may potentially be useful for monitoring patients in the home environment, thus encouraging the population to participate in more personalized healthcare.

Propionibacterium acnes-Derived Circulating Immune Complexes in Sarcoidosis Patients.

Propionibacterium acnes is a potential etiologic agent of sarcoidosis and a dysregulated immune response to the commensal bacterium is suspected to cause granuloma formation. P. acnes-derived insoluble immune complexes were recently demonstrated in sinus macrophages of sarcoidosis lymph nodes, suggesting local proliferation of the bacterium in affected organs. In the present study, we developed a method for detecting P. acnes-derived immune complexes in human blood by measuring the concentration of P. acnes-specific lipoteichoic acid (PLTA) detectable after an antigen retrieval pretreatment of plasma samples. Before pretreatment, anti-PLTA antibody was detected and PLTA could not be detected, in all plasma samples from 51 sarcoidosis patients and 35 healthy volunteers. After pretreatment, however, a significant level of PLTA (>105 ng/mL) was detected in 33 (65%) sarcoidosis patients and 5 (14%) control subjects, with 86% specificity and 65% sensitivity for sarcoidosis. In both groups, plasma anti-PLTA antibody titers did not differ between samples with and without detection of PLTA. PLTA levels were abnormally increased (>202 ng/mL) in 21 (41%) sarcoidosis patients. These findings suggest that P. acnes-derived circulating immune complexes present in human blood are abnormally increased in many sarcoidosis patients, presumably due to local proliferation of the bacterium in the affected organs.

Detection of biologically important anions in aqueous media by dicationic azaborines bearing ammonio or phosphonio groups.

New cationic triarylboranes bearing ammonio or phosphonio groups on the periphery were synthesized from a common intermediate, a dibromodibenzoazaborine. These cationic molecules are soluble in highly polar organic solvents as well as water, and they exhibit strong light absorption and photoluminescence emission in water. Complexation of the cationic azaborines with fluoride and cyanide ions in aqueous media proceeded and could be monitored by NMR, UV/Vis, and fluorescence spectroscopy.

Synthesis and reactivity of a bis(dimesitylboryl)azaborine and its fluoride sensing ability.

An azaborine bearing two dimesitylboryl groups on its periphery showed very strong light absorption and moderate photo-luminescence emission; the reaction of the title compound with fluoride ion resulted in multi-step fluoride ion complexation on the boron atoms of the dimesitylboryl groups, producing mono- and bisfluoroborates.

Relationship between mucin expression of gastric intramucosal signet ring cell carcinoma and its background mucosa.

The intramucosal lesion of gastric signet ring cell carcinoma (SIG) is known to form a layered structure (LS) that simulates mucin expression in ordinary gastric mucosa. In this study, we suspected the influence of background mucosa on the formation of LS and performed histopathological analysis. We examined 35 cases of intramucosal SIG with a maximum diameter of 30 mm or less. The LS patterns were classified into those with a layer of MUC6-positive cells (complete pattern, CP) and those lacking this layer (incomplete pattern, ICP). The relationship between LS patterns and the characteristics of the background mucosa, the expression of MUC2 (intestinal-type mucin antigen), MUC5AC (foveolar-type mucin antigen), and Ki-67 (the marker of cell proliferation activity) was examined by histochemistry and immunohistochemistry. Intestinal metaplasia in the background mucosa and MUC2 expression were frequently observed in cases with ICP. Ki-67-positive cells were much more and they were distributed more widely in the lesion of cases with ICP alone than in the other cases. Mucin expression and LS formation of gastric SIG are strongly influenced by its background mucosa. The cases completely lacking MUC6 expression may have higher malignant potential.

Regulation of REG4 Expression and Prediction of 5-Fluorouracil Sensitivity by CDX2 in Ovarian Mucinous Carcinoma.

BACKGROUND/AIM: The biological importance of the caudal-related homeobox transcription factor CDX2 in acquiring resistance to anticancer drugs has been studied in ovarian mucinous carcinoma. CDX2 promotes the expression of multidrug resistance 1 (MDR1) and confers resistance to paclitaxel. The regenerating islet-derived family member 4 (REG4) gene is a potential target gene of CDX2. In this study, we investigated the relationship between the expression of CDX2 and Reg IV and the regulation of Reg IV expression and examined novel chemotherapeutic regimens. MATERIALS AND METHODS: The regulation of Reg IV expression by CDX2 and sensitivity of 5-fluorouracil (5-FU) were evaluated using ovarian mucinous cancer cell lines. RESULTS: The correlation of CDX2 with Reg IV expression was demonstrated in ovarian mucinous carcinoma. Reg IV expression was enhanced by transfection of CDX2 and was suppressed by inhibition of CDX2 expression. OMC-3 cells with ectopically overexpressed CDX2 showed enhanced apoptosis and sensitivity to 5-FU. CONCLUSION: CDX2 promotes resistance to paclitaxel and sensitivity to 5-FU. Novel 5-FU-based chemotherapy based on CDX2 may be used in ovarian mucinous carcinoma.

The quantitative analysis of the human papillomavirus DNA load in submandibular gland lesions with droplet digital polymerase chain reaction.

BACKGROUND: The relationship between infection with human papillomavirus (HPV) and tumorigenesis of salivary gland remains controversial. OBJECTIVES: This study explored the relationship between HPV and salivary gland lesions as well as that of the HPV infection status and p16INK4A immunoreactivity. The HPV DNA loads were also quantitatively evaluated. MATERIALS AND METHODS: Tissue samples from 31 submandibular gland lesions were evaluated. p16INK4A immunohistochemical (IHC) staining, nested polymerase chain reaction (PCR), DNA sequencing, and droplet digital PCR (ddPCR) were performed. RESULTS: Non-neoplastic lesion, benign tumors, and malignant tumors were noted in 9, 16, 6 cases, respectively. p16INK4A immunoreactivity was higher in malignant tumors than in benign tumors (50.0% vs. 6.3%). Single PCR with MY09/11 found that all samples were negative. Nevertheless, nested PCR revealed a high HPV-DNA positivity rate of 96.8%. No relationship between the HPV status and p16INK4A immunoreactivity was shown. HPV-18 was the only subtype identified in this study. ddPCR showed significantly lower HPV-18 DNA loads in submandibular gland lesions than in oropharyngeal cancers. CONCLUSIONS: HPV-DNA positivity and p16INK4A-immunoreactivity were not correlated in submandibular gland lesions. The loads of HPV DNA detected in this study were small. HPV positivity therefore may not be associated with tumorigenesis of the submandibular gland.

Useful Application of Immunostaining to Malignant Pleural Effusion among Lao People in Vientiane Capital, Lao PDR

Background: Pathology and laboratory medicine (PALM) services are limited in low-resource countries, such as Lao PDR. Patients with malignant pleural effusion (MPE) are not properly diagnosed and treated in these situations. The purpose of this study is to confirm the usefulness of immunocytochemistry in MPE to identify the histological type and probable primary site of cancer of MPE and to discuss its usefulness in low-resource countries, such as Laos. Methods: We retrospectively reviewed glass slides of pleural effusion sent to the Department of Pathology at the University of Health Sciences from the central hospitals for cytological screening from January 2012 to December 2016. The cytological review, cell transfer and immunocytochemical staining were performed at Tokyo Medical and Dental University. Among 81 cases of MPE from Laos, 66 cases of malignant tumors that contained enough tumor cells were included in this study, and the slides were screened with 14 primary antibodies to classify the histological type and identify the probable primary site of carcinoma. Results: Among the 66 cases, 34 cases (52%) were of female patients, and 32 cases (48%) were of male patients. The patients' ages ranged from 28 to 88 years with an average of 58 years. The immunocytochemical study identified 32 cases (49%) of primary lung adenocarcinoma, two cases (3%) of malignant mesothelioma, one case (1.5%) of breast/gynecological carcinoma, one case (1.5%) of T cell lymphoma, and one case (1.5%) of B cell lymphoma. Twenty-nine cases (43.5%) were classified as carcinoma not otherwise specified. Pulmonary small cell carcinoma/squamous cell carcinoma and metastatic colon, prostate, and liver carcinoma were not identified among the cases. Conclusions: Immunocytochemistry is a useful ancillary method in MPE diagnostics. This method could be applied in the pathological laboratories in low- or middle-resource countries, such as Laos.

Helicobacter pylori invades the gastric mucosa and translocates to the gastric lymph nodes.

Helicobacter pylori has been considered to be non-invasive and to rarely infiltrate the gastric mucosa, even though there is an active Th1 immune response in the lamina propria of the H. pylori-infected stomach. To elucidate whether H. pylori invades the lamina propria and translocates to the gastric lymph nodes, we examined H. pylori in formalin-fixed and paraffin-embedded tissue sections of stomach and gastric lymph nodes obtained from 51 cancer patients using real-time PCR and immunohistochemistry (IHC) with a novel anti-H. pylori monoclonal antibody that recognizes lipopolysaccharides. Fresh gastric lymph nodes were used to culture for H. pylori. In 46 patients with H. pylori in the stomach, the bacterium was found in the lymph nodes from 21 patients by culture, 37 patients by PCR, and 29 patients by IHC. H. pylori captured by macrophages was found in the lamina propria of 39 patients. In the lymph nodes, the bacterium was found in many macrophages and a few interdigitating dendritic cells at the paracortical areas. H. pylori was also found in the intracellular canaliculi of parietal cells in 21 patients, but intracytoplasmic invasion into gastric epithelial cells was not identified. When compared to the commercially available anti-H. pylori antibodies, the novel antibody showed the highest sensitivity to detect H. pylori-positive macrophages, whereas no difference was found for H. pylori in the mucous layer. The H. pylori-positive macrophages in the lamina propria correlated with chronic gastritis as well as translocation of such cells to the lymph nodes. These results suggest that H. pylori-induced gastric epithelial damage allows the bacteria to invade the lamina propria and translocate to the gastric lymph nodes, which may chronically stimulate the immune system. The bacteria captured by macrophages, whether remaining alive or not, may contribute to the induction and development of H. pylori-induced chronic gastritis.