Additional chemoradiotherapy for superficial esophageal squamous cell carcinoma after near-circumferential or full-circumferential noncurative endoscopic submucosal dissection: a retrospective study.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a potentially efficient therapeutic intervention for superficial esophageal cancer. Additional treatment such as chemoradiotherapy (CRT) or esophagectomy is recommended in cases of muscularis mucosa invasion with positive resection margins or lymphovascular invasion or submucosal layer invasion, which are considered noncurative ESD, due to an increased risk of lymph node metastasis. However, the adequacy of additional CRT after near-circumferential or full-circumferential noncurative ESD has not been fully discussed. In this study, we retrospectively evaluated the efficacy and toxicity of additional CRT for superficial esophageal squamous cell carcinoma (SCC) after near-circumferential or full-circumferential noncurative ESD, which was defined as a mucosal defect measuring ≥ 3/4 of the esophageal circumference. METHODS: We retrospectively evaluated 24 patients who received additional CRT for superficial esophageal SCC after near-circumferential or full-circumferential noncurative ESD between 2012 and 2018. Elective nodal irradiation (ENI) was performed in all patients and boost irradiation (BI) was performed after ENI in 4 patients with positive resection margins. The prescription doses of ENI and BI were 41.4 Gy in 23 fractions and 9 Gy in 5 fractions, respectively. Concurrent chemotherapy (a combination of cisplatin or nedaplatin and 5-fluorouracil) was administered to all patients. RESULTS: The 3-year and 5-year overall survival rates were 92% and 78%, respectively, while the 3-year and 5-year progression-free survival rates were 83% and 70%, respectively. Grade 2 esophageal stenosis occurred in 8 (33%) patients. There was no case of Grade 3 or worse esophageal stenosis. Among them, 4 (17%) patients developed stenosis before additional CRT, which persisted after the completion of additional CRT. The remaining 4 (17%) patients developed de novo stenosis within 5 months following the completion of additional CRT. One patient (4%) still requires regular bougie dilation. Grade 3 and Grade 4 acute toxicity, including anemia, neutropenia, thrombocytopenia, and esophagitis occurred in 1 (4%) and 0 (0%), 6 (25%) and 1 (4%), 1 (4%) and 0 (0%), and 1 (4%) and 0 (0%) patients, respectively. One (4%) patient who underwent salvage CRT for the out-of-field lymph node recurrence died with acute myeloid leukemia. CONCLUSIONS: Additional CRT is a viable treatment option even in patients who have undergone near-circumferential or full-circumferential noncurative ESD. Esophageal stenosis after additional CRT following near-circumferential or full-circumferential noncurative ESD is manageable and acceptable.

Platelet-activating factor contracts guinea pig esophageal muscularis mucosae by stimulating extracellular Ca2+ influx through diltiazem-insensitive Ca2+ channels.

Platelet-activating factor (PAF) is expected to increase esophageal motility. However, to the best of our knowledge, this has not been examined. Thus, we investigated the contractile effects of PAF on guinea pig (GP) esophageal muscularis mucosae (EMM) and the extracellular Ca2+ influx pathways responsible. PAF (10-9-10-6 M) contracted EMM in a concentration-dependent manner. PAF (10-6 M)-induced contractions were almost completely suppressed by apafant (a PAF receptor antagonist, 3 × 10-5 M). In EMM strips, PAF receptor and PAF-synthesizing/degrading enzyme mRNAs were detected. PAF (10-6 M)-induced contractions were abolished by extracellular Ca2+ removal but were not affected by diltiazem [a voltage-dependent Ca2+ channel (VDCC) inhibitor, 10-5 M]. PAF (10-6 M)-induced contractions in the presence of diltiazem were significantly suppressed by LOE-908 [a receptor-operated Ca2+ channel (ROCC) inhibitor, 3 × 10-5 M], SKF-96365 [an ROCC and store-operated Ca2+ channel (SOCC) inhibitor, 3 × 10-5 M], and LOE-908 plus SKF-96365. Among the tested ROCC/SOCC-related mRNAs, Trpc3, Trpc6, and Trpv4/Orai1, Orai3, and Stim2 were abundantly expressed in EMM strips. These results indicate that PAF potently induces GP EMM contractions that are dependent on extracellular Ca2+ influx through ROCCs/SOCCs, and VDCCs are unlikely to be involved.

How does the lower urinary tract contribute to bladder sensation? ICI-RS 2023.

AIM: Bladder sensation is critical for coordinating voluntary micturition to maintain healthy bladder function. Sensations are initiated by the activation of sensory afferents that innervate throughout the bladder wall. However, the physiological complexity that underlies the initiation of bladder sensory signaling in health and disease remains poorly understood. This review summarises the latest knowledge of the mechanisms underlying the generation of bladder sensation and identifies key areas for future research. METHODS: Experts in bladder sensory signaling reviewed the literature on how the lower urinary tract contributes to bladder sensation and identified key research areas for discussion at the 10th International Consultation on Incontinence-Research Society. RESULTS: The importance of bladder sensory signals in maintaining healthy bladder function is well established. However, better therapeutic management of bladder disorders with exaggerated bladder sensation, including overactive bladder syndrome (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS) is limited by a lack of knowledge in a number of key research areas including; the contribution of different nerves (pudendal, pelvic, hypogastric) to filling sensations in health and disease; the relative contribution of stretch sensitive (muscular) and stretch-insensitive (mucosal) afferents to bladder sensation in health and disease; the direct and indirect contributions of the muscularis mucosae to bladder contraction and sensation; and the impact of manipulating urothelial release factors on bladder sensation. CONCLUSION: Disturbances in bladder sensory signaling can have severe consequences for bladder sensation and function including the development of OAB and IC/BPS. Advancing therapeutic treatments for OAB and IC/BPS requires a deeper understanding of the mechanisms underlying the generation of bladder sensation, and key areas for future research have been identified.

Hemorrhagic bowel syndrome in dairy cattle: Gross, histological, and microbiological characterization.

Hemorrhagic bowel syndrome (HBS) is a sporadic and fatal disease of predominantly lactating dairy cattle, characterized by segmental hemorrhage and luminal clot formation in the small intestine. Although, Clostridium perfringens and Aspergillus fumigatus have been associated with HBS, the pathogenesis and cause are currently unknown. In this study, 18 naturally occurring cases of HBS (7 necropsied immediately following euthanasia, 11 with 12-48 hour postmortem intervals) were investigated to characterize the pathology and the intestinal microbiome. Hemorrhagic bowel syndrome was characterized by a single small-intestinal, intramucosal hematoma with dissection of the lamina muscularis mucosae. In most cases necropsied immediately after euthanasia (4/7), the intestinal mucosa proximal to the hematoma contained 9 to 14, dispersed, solitary or clustered, erosions or lacerations measuring 4 to 45 mm. In 77% (37/48) of these mucosal lesions, microscopic splitting of the lamina muscularis mucosae comparable to the hematoma was present. These findings suggest the intramucosal hematoma to originate from small mucosal erosions through dissecting hemorrhage within the lamina muscularis mucosae. No invasive fungal growth was observed in any tissue. Bacteriological cultivation and nanopore sequencing showed a polymicrobial population at the hematoma and unaffected intestine, with mostly mild presence of C perfringens at selective culture. Gross and microscopic lesions, as well as the culture and sequencing results, were not in support of involvement of C perfringens or A fumigatus in the pathogenesis of HBS.

Functional nitrergic innervation of smooth muscle structures in the mucosa of pig lower urinary tract.

Neurally released nitric oxide (NO) functions as an inhibitory neurotransmitter of urethral but not detrusor smooth muscles while relaxing bladder vasculature and muscularis mucosae (MM). Here, the distribution of nitrergic nerves was examined in the mucosa of pig lower urinary tract using immunohistochemistry, and their vasodilatory functions were studied by measuring arteriolar diameter changes. Properties of smooth muscle cells in the lamina propria (SMC-LP) of urethra and trigone were also investigated using florescence Ca2+ imaging. In the bladder mucosa, neuronal nitric oxide synthase (nNOS)-immunoreactive nitrergic fibres projected to suburothelial arterioles and venules. Perivascular nitrergic nerves were intermingled with but distinct from tyrosine hydroxylase (TH)-immunoreactive sympathetic or calcitonin gene-related peptide (CGRP)-immunoreactive afferent nerves. MM receive a nitrergic but not sympathetic or afferent innervation. In the mucosa of urethra and trigone, nitrergic nerves were in close apposition with sympathetic or afferent nerves around suburothelial vasculature but did not project to SMC-LP. In suburothelial arterioles of bladder and urethra, N ω-nitro-L-arginine (L-NA, 100 µM), an NOS inhibitor, enhanced electrical field stimulation (EFS)-induced sympathetic vasoconstrictions, while tadalafil (10 nM), a phosphodiesterase type 5 (PDE5) inhibitor, suppressed the vasoconstrictions. SMC-LP developed asynchronous spontaneous Ca2+ transients without responding to EFS. The spontaneous Ca2+ transients were enhanced by acetylcholine (1 µM) and diminished by noradrenaline (1 µM) but not SIN-1 (10 µM), an NO donor. In the lower urinary tract mucosa, perivascular nitrergic nerves appear to counteract the sympathetic vasoconstriction to maintain the mucosal circulation. Bladder MM but not SMC-LP receive an inhibitory nitrergic innervation.

Comparative effects of angiotensin II on the contractility of muscularis mucosae and detrusor in the pig urinary bladder.

To explore contractile actions of angiotensin II (ATII) on the muscularis mucosae (MM) of the bladder, ATII-induced contractions were compared between MM and the detrusor smooth muscle (DSM) of the pig bladder by isometric tension recordings. Effects of ATII on spontaneous Ca2+ transients in MM were visualized using Cal-520 fluorescence. ATII receptor type 1 (ATR1) expression in MM and DSM was also examined by immunohistochemistry. ATII (1 nM-1 µM) caused phasic contractions of MM in a concentration-dependent manner, while ATII (10 nM-10 µM) had no or marginal effects on DSM contractility. ATII (100 nM)-induced MM contractions had an amplitude of approximately 70% of carbachol (1 µM)-induced or 90% of U46619 (100 nM)-induced contractions. Candesartan (10 nM), an ATR1 blocker, prevented the contractile effects of ATII (1 nM) in MM, while ATR1 immunofluorescence was greater in MM than DSM. ATII (10-100 pM) increased the frequency but not the amplitude of spontaneous Ca2+ transients in MM. Both urothelium-intact and -denuded MM strips developed comparable spontaneous phasic contractions, but ATII, carbachol and U46619-induced contractions were significantly larger in urothelium-denuded than urothelium-intact MM strips. In conclusion, the MM appears to have a much greater sensitivity to ATII compared with DSM that could well sense circulating ATII, suggesting that MM may be the predominant target of contractile actions induced by ATII in the bladder while the urothelium appears to inhibit MM contractility.

Contractile elements and their sympathetic regulations in the pig urinary bladder: a species and regional comparative study.

Contractile behaviour of the urinary bladder and its sympathetic inhibition during storage phases are not well understood. Here, we explore muscularis mucosae (MM) as a predominant mucosal contractile element and the capability of sympathetic nerves to relax detrusor smooth muscle (DSM) or MM. Distribution of α-smooth muscle actin (α-SMA)-immunoreactive cells was compared in pig, human, guinea pig, rat and mouse bladders by immunohistochemistry, while contractility of the bladder mucosa was compared in these species by isometric tension recordings. In pig, human and guinea pig bladders, DSM and MM located in the lamina propria expressed α-SMA immunoreactivity, while both rat and mouse bladders lacked a MM. Consistent with this presence or absence of MM, bladder mucosa of pig, human and guinea pig but not rat and mouse developed spontaneous phasic contractions (SPCs). Distribution of tyrosine hydroxylase (TH)-immunoreactive sympathetic nerve fibres was compared in pig DSM, MM, trigone and urethra, as were their sympathetic nerve-evoked contractile/relaxing responses examined. In pig DSM or MM, where TH-immunoreactive sympathetic fibres exclusively projected to the vasculature, sympathetic relaxations were difficult to demonstrate. In contrast, sympathetic contractions were invariably evoked in pig trigone and urethra where the smooth muscle cells receive TH-immunoreactive sympathetic innervations. Thus, SPCs of bladder mucosa appear to predominantly arise from the MM displaying species differences. Despite the currently accepted concept of sympathetic nerve-mediated DSM relaxation during the storage phase, it is unlikely that neurally released noradrenaline acts on ß-adrenoceptors to relax either DSM or MM due to the anatomical lack of sympathetic innervation.

En bloc resection improves the identification of muscularis mucosae in non-muscle invasive bladder cancer.

PURPOSE: The T1 substage, according to the relationship between muscularis mucosae (MM) and tumors, is a promising prognostic factor for T1 bladder cancer. However, the identification rate of MM is low in specimens, and it is, therefore, not widely used in clinical practice. In this study, we investigated whether en bloc resection of non-muscle invasive bladder cancer (NMIBC) could improve the identification of muscularis mucosae (MM), which may further accurate identification of the T1 substage. PATIENTS AND METHODS: Specimens from 158 patients with primary NMIBC were retrospectively reviewed by two independent pathologists to assess the presence of MM and stratify the T1 substage. Of 158 specimens, 70 specimens were obtained via TURBt with a plasma kinetic loop and 88 were obtained via front-firing potassium-titanyl-phosphate (KTP) green-light laser en bloc resection. Univariable and multivariable logistic regression models were used to analyze the relationship between the clinical characteristics and the presence of MM. RESULTS: The mean age was 58.22 years (range 18-85 years). Multivariable logistic regression analysis showed that the KTP laser resection method was associated with the presence of MM in specimens (P = 0.008). In addition, tumors with smaller sizes, which could also be en bloc resected with TURBt (e.g., ≤1 cm), had a higher presence of MM (P = 0.047). CONCLUSIONS: En bloc resection improves the identification rate of MM, which may enhance the accurate identification of the T1 substage.

Management and risk factors for incomplete resection associated with jumbo forceps polypectomy for diminutive colorectal polyps: a single-institution retrospective study.

BACKGROUND: Cold forceps polypectomy is simple and widely used in clinical practice. However, there are concerns about the risk of incomplete resection using this technique. In recent years, it has been reported that polypectomy with jumbo forceps (JF) is an effective treatment modality for diminutive polyps (DPs) because JF are able to remove large tissue samples with the combined advantage of a higher complete histological resection rate for DPs than standard forceps. To our knowledge, no studies have evaluated the risk factors for incomplete resection when polypectomy with JF is performed for DPs. METHODS: From among 1129 DPs resected using JF at Hiroshima City Asa Citizens Hospital between November 2015 and December 2016, we retrospectively evaluated the clinical outcomes of 999 tumors with known histopathology and investigated the relationship between incomplete resection and clinicopathological factors. RESULTS: Most lesions [985 (87%)] were low-grade dysplasia and 14 (1%) were high-grade dysplasia. The en bloc resection rate was 92% (918/999) and the histological en bloc resection rate was 78% (777/999). Multivariate analysis showed that the significant independent predictors of incomplete resection were tumor size ≥ 4 mm [odds ratio (OR) 3.8; 95% confidence interval (CI) 2.65-5.37; p < 0.01], non-tangential direction of forceps in relation to the tumor (OR 1.73; 95% CI 1.21-2.45; p < 0.01), and lack of muscularis mucosae in the pathological specimen (OR 15.7; 95% CI 9.16-27.7; p < 0.01). CONCLUSIONS: This study identified significant independent predictors of incomplete resection of DPs which may be helpful when planning polypectomy with JF.

Observation of the cytoarchitecture of the human esophageal mucosa with special attention to the lamina muscularis mucosae and the distribution of lymphatic vessels.

The cytoarchitecture of the esophageal mucosa was examined by using light microscopy, transmission electron microscopy, and scanning electron microscopy. The cytoarchitecture of the muscularis mucosae varied greatly among the cervical, thoracic, and abdominal esophagus, especially in the cervical esophagus, the muscularis mucosae suffered a loss and the distribution of lymphatic vessels also varied according to the site. It was suggested that these morphological differences would have a strong influence on the infiltration of esophageal cancer and the mode of lymph node metastasis.

Telocytes role during the postnatal development of the Mongolian gerbil jejunum.

Telocytes are recently categorised CD34-positive interstitial cells that comprise the cells which were previously called interstitial Cajal-like cells (ICLCs). These were detected in the stroma of various organs such as the prostate, lungs, mammary glands, liver, gallbladder, and jejunum, among others. Several functions have been proposed for telocytes, such as a supportive role in smooth muscle contraction and immune function in adult organs, and tissue organisation and paracrine signalling during development, as well as others. In the jejunum, little is known about the function of telocytes in the adult organ, or is there any information about when these cells develop or if they could have an auxiliary role in the development of the jejunum. The present study employed histological, immunohistochemical and immunofluorescence techniques on histological sections of the jejunum of Mongolian gerbil pups on two different days of postnatal development of the jejunum, covering the maturation period of the organ. By immunolabelling for CD34, it was observed that telocytes are already present in the jejunum during the first week of postnatal life and exist in close association with the developing muscularis mucosae, which are therefore TGFß1-positive. The telocytes are still present at the end of the first month of life, and a portion of them present co-localisation with c-Kit. Fibroblast-like cells, which are exclusively c-Kit-positive, are also observed, which may indicate the presence of interstitial Cajal cells (ICCs). Finally, it can be hypothesised that a portion of the telocytes may give rise to ICCs, which are c-Kit-positive but CD34 negative.

Some observations on Barrett esophagus and associated dysplasia.

Biopsy samples from esophageal columnar metaplasia and dysplasia are commonly encountered in Western pathology practice and knowing a few pitfalls can save both pathologists and patients a great deal of anxiety. Herein we discuss criteria for Barrett esophagus, evaluation of dysplasia, and some pitfalls in reviewing endoscopic mucosal resections. Also included is a summary of suggested follow-up for patients with Barrett esophagus.

Immunohistochemical differentiation between muscularis mucosae and muscularis propria for improving the staging of bladder cancer in patients undergoing transurethral resection of bladder tumours.

Microscopic differentiation between muscularis mucosae (MM) and muscularis propria (MP) of the bladder in the material obtained during transurethral resection (TUR) remains difficult. The study was aimed at determination of the usefulness of immunohistochemical staining in this context. Forty-seven TUR specimens were stained with 5 mouse anti-human antibodies: anti-desmin, anti-filamin, anti-type IV collagen, anti-smoothelin, and anti-vimentin. Slides were assessed under light microscopy and the intensity of the immune reaction within MM and MP was evaluated on a four-level visual scale as follows: negative (0) and weakly (1), moderately (2), or strongly (3) positive. MM was identified in 27 patients (57.4%). The modal values of reaction intensity in MM and MP was 0 and 2 for desmin (p > 0.05), 2 and 2 for filamin (p = 0.01), 2 and 2 for type IV collagen (p > 0.05), 1 and 2 for smoothelin (p = 0.03), and 2 and 0 for vimentin (p = 0.02), respectively. Identical intensity within MM and MP was observed in 7.1%, 28.6%, 20%, 30.1%, 5.6%, respectively. Immunohistochemistry can help differentiate between MM and MP in TUR specimens. As of yet, no single marker can reliably differentiate between MM and MP; however, a combination of anti-filamin, anti-smoothelin, and anti-vimentin antibodies may be reasonable for diagnostic purposes.

Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder.

We investigated the role of TRPV4 channels (TRPV4) in regulating the contractility of detrusor smooth muscle (DSM) and muscularis mucosae (MM) of the urinary bladder. Distribution of TRPV4 in DSM and MM of guinea-pig bladders was examined by fluorescence immunohistochemistry. Changes in the contractility of DSM and MM bundles were measured using isometric tension recording. Intracellular Ca(2+) dynamics were visualized by Cal-520 fluorescent Ca(2+) imaging, while membrane potential changes were recorded using intracellular microelectrode technique. DSM and MM expressed TRPV4 immunoreactivity. GSK1016790A (GSK, 1 nM), a TRPV4 agonist, evoked a sustained contraction in both DSM and MM associated with a cessation of spontaneous phasic contractions in a manner sensitive to HC-067047 (10 µM), a TRPV4 antagonist. Iberiotoxin (100 nM) and paxilline (1 µM), large conductance Ca(2+)-activated K(+) (BK) channel blockers restored the spontaneous contractions in GSK. The sustained contractions in DSM and MM were reduced by nifedipine (10 µM), a blocker of L-type voltage-dependent Ca(2+) channels (LVDCCs) by about 40 % and by nominally Ca(2+)-free solution by some 90 %. GSK (1 nM) abolished spontaneous Ca(2+) transients, increased basal Ca(2+) levels and also prevented spontaneous action potential discharge associated with DSM membrane hyperpolarization. In conclusion, Ca(2+) influx through TRPV4 appears to activate BK channels to suppress spontaneous contractions and thus a functional coupling of TRPV4 with BK channels may act as a self-limiting mechanism for bladder contractility during its storage phase. Despite the membrane hyperpolarization in GSK, Ca(2+) entry mainly through TRPV4 develops the tonic contraction.

Lymph node metastasis risk according to the depth of invasion in early gastric cancers confined to the mucosal layer.

BACKGROUND: Early gastric cancers (EGCs) within the mucosal layer of the gastric wall have a small risk of lymph node (LN) metastasis. METHODS: We reviewed clinicopathology data for patients who underwent surgery for EGC between 2001 and 2013 at the National Cancer Center, Korea. Poisson regression analyses were performed to compare the risk of LN metastasis according to the depth of tumor invasion in patients with mucosal EGCs. RESULTS: Among the 1776 EGC patients included, 580 (32.7 %) had tumors confined to the lamina propria (LP; LP group) and 1196 (67.3 %) had tumors invading the muscularis mucosae (MM; MM group). Seventy-one patients (4.0 %) had LN metastasis, and the MM group had a significantly higher rate of LN metastasis (59 patients, 4.9 %) than the LP group (12 patients, 2.1 %; P = 0.004). A multivariate analysis showed that tumors invading the MM (adjusted risk ratio 1.95; P = 0.045) were significantly associated with LN metastasis in addition to well-known risk factors, including tumor size greater than 3 cm, presence of ulceration, undifferentiated histologic type, and lymphovascular invasion. The incidence of LN metastasis was 1.87 % (95 % confidence interval 0.23-6.59 %) within tumors invading the MM that met the expanded criterion for endoscopic resection of differentiated histologic type of size 3 cm or smaller with ulceration. LN metastasis was not found in tumors meeting the absolute criteria for endoscopic resection. CONCLUSIONS: EGCs invading the MM had a higher rate of lymph node metastasis than those confined to the LP. Further study is needed to evaluate whether different curative treatment criteria are needed for LP-confined and MM-invading EGCs.

Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis.

BACKGROUND AND AIM: Recent advances in endoscopic technology have allowed many T1 colorectal carcinomas to be resected endoscopically with negative margins. However, the criteria for curative endoscopic resection remain unclear. We aimed to identify risk factors for nodal metastasis in T1 carcinoma patients and hence establish the indication for additional surgery with lymph node dissection. METHODS: Initial or additional surgery with nodal dissection was performed in 653 T1 carcinoma cases. Clinicopathological factors were retrospectively analyzed with respect to nodal metastasis. The status of the muscularis mucosae (MM grade) was defined as grade 1 (maintenance) or grade 2 (fragmentation or disappearance). The lesions were then stratified based on the risk of nodal metastasis. RESULTS: Muscularis mucosae grade was associated with nodal metastasis (P = 0.026), and no patients with MM grade 1 lesions had nodal metastasis. Significant risk factors for nodal metastasis in patients with MM grade 2 lesions were attribution of women (P = 0.006), lymphovascular infiltration (P < 0.001), tumor budding (P = 0.045), and poorly differentiated adenocarcinoma or mucinous carcinoma (P = 0.007). Nodal metastasis occurred in 1.06% of lesions without any of these pathological factors, but in 10.3% and 20.1% of lesions with at least one factor in male and female patients, respectively. There was good inter-observer agreement for MM grade evaluation, with a kappa value of 0.67. CONCLUSIONS: Stratification using MM grade, pathological factors, and patient sex provided more appropriate indication for additional surgery with lymph node dissection after endoscopic treatment for T1 colorectal carcinomas.

[Barrett's esophagus and carcinoma: Recommendations of the S2k guideline 2014 and the S3 guideline 2015]. / Barrett-Ösophagus und Barrett-Karzinom: Empfehlungen gemäß S2k­Leitlinie von 2014 und S3­Leitlinie von 2015.

In the current S2k guideline for gastroesophageal reflux disease and the new S3 guideline for esophageal cancer, histopathological evaluation of Barrett's esophagus has been revised and supplemented. The histological diagnosis of Barrett's esophagus still requires the proof of a specialized intestinal metaplastic epithelium (columnar epithelium with goblet cells). Barrett mucosa must be classified as negative, unclear/doubtful, and positive concerning the intraepithelial neoplasia (IEN)/dysplasia according to the current WHO guideline. Each IEN should be confirmed by an external second opinion due to poor interobserver variability. The pathological classification is of decisive importance here, since the recommended monitoring intervals are based solely on the ground of proved IEN. Risk factors in endoscopic resection specimens such as depth of infiltration (m1-m4; sm1-sm3; distance in µm); angioinvasion (L, V); grading and lateral/basal resection margin have to be reported. In surgical specimens, the reference of the tumor center to the gastroesophageal junction and in the neoadjuvant situation the tumor regression should be documented.

Morphological organisation of the digestive tract in the stream catfish Pseudecheneis sulcatus (McClelland).

We describe the histological organisation and mucin content in the digestive tract of the stream catfish Pseudecheneis sulcatus. The aim is to find the modifications of the digestive tract in relation to food resources of its habitat. The oesophageal mucosa consists of stratified squamous epithelium with many mucous-secreting cells. The thick muscularis contains an inner longitudinal and outer circular, striated muscle cells. The stomach is J-shaped and shows 6-7 thick mucosal folds that are separated from the submucosa by an organised muscularis mucosae. The mucosa consists of superficial cells with mucin granules, and deeper simple tubular gastric glands in cardia and fundus, but absent in pyloric region. The glandular epithelium shows oxynticopeptic cells containing zymogen granules and abundant tubulo-vesicular bodies. We provide evidence that the latter arise by budding from smooth endoplasmic reticulum and reach the apical cytoplasm. The anterior intestine shows longer mucosal folds with goblet cells (GC). GC are more in the posterior intestine and highest in the rectum. Myenteric neurons with myelinated and non-myelinated axons innervate the intrinsic musculature from stomach to rectum. Many stem cells are evident in the basal intestinal epithelium. They show darker nuclei and undifferentiated organelles. Mucin histochemistry reveals the predominance of neutral mucin (PAS+ positive) from oesophagus to rectum, and neutral and acidic mucin (alcian blue+, pH 2.5) in the posterior intestine to the rectum, with few GC colocalizing both. Ultrastructural features suggest that the species is adapted to omnivory and this is reflected in the predominance of neutral mucin in the digestive tract.

Double-endoscope endoscopic submucosal dissection for the treatment of early gastric cancer accompanied by an ulcer scar (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) for early gastric cancer accompanied by an ulcer scar remains challenging. Several counter-traction techniques have been attempted to facilitate ESD, but a standard procedure remains to be established. OBJECTIVE: To evaluate the efficacy and safety of double-endoscope ESD by using a single light source in patients with early gastric cancer accompanied by an ulcer scar. DESIGN: Single center, retrospective study. SETTING: Kitasato University East Hospital. PATIENTS: A total of 30 early gastric cancers with ulcer scars were treated by double-endoscope ESD in 30 patients from October 2008 through May 2012. INTERVENTION: Double-endoscope ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection rate, complete resection rate, treatment time, and adverse events. RESULTS: The use of two endoscopes for ESD provided a good field of vision and allowed counter-traction to be applied to the lesion, clearly facilitating submucosal dissection. Because only a single light source was used, the working space of the endoscope room was not compromised. Moreover, it was unnecessary to prepare another light source or to coordinate image filing. The en bloc resection rate and complete resection rate were 100% and 90%, respectively, and the median treatment time was 80 minutes. As compared with historical control data obtained before the introduction of double-endoscope ESD, the rate of cutting into the specimen was significantly lower (7% vs 35%; P = .01). No serious adverse events occurred during the procedure. Postoperatively, however, 3 patients (10%) had delayed hemorrhage, and 1 (3.3%) had a delayed perforation. LIMITATIONS: Single-center, nonrandomized study. CONCLUSION: Our experience indicates that our procedure for double-endoscope ESD is useful and feasible in patients with early gastric cancer accompanied by an ulcer scar.

A phase II study of endoscopic submucosal dissection for superficial esophageal neoplasms (KDOG 0901).

BACKGROUND: Most previous studies of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms were retrospective; prospective studies are scant. OBJECTIVE: To prospectively assess the efficacy and safety of ESD for superficial esophageal neoplasms. DESIGN: Phase II study. SETTING: University hospital. PATIENTS: Fifty-two patients (median age 68 years; 48 men) who had a histologic diagnosis of superficial esophageal cancer without metastasis on CT or high-grade intraepithelial neoplasia (HGIN) were enrolled from April 2009 through November 2011. INTERVENTION: ESD was used to treat 56 lesions. All procedures were done by 4 endoscopists who each had previously performed ESD in more than 100 patients with gastric tumors. MAIN OUTCOME MEASUREMENTS: The primary endpoint was the R0 resection rate, and secondary endpoints were the safety and the rate of accurately diagnosing tumor depth on endoscopic examination. RESULTS: The median treatment time was 69 minutes (24-168 minutes). The histopathologic diagnosis was squamous cell carcinoma in 49 lesions, HGIN in 5, and tubular adenocarcinoma in 2. The en bloc resection rate and R0 resection rate were 100% and 94.6%, respectively. The rates of adverse events during ESD and after ESD were 22.2% and 53.8%, respectively, but most events were mild. One patient (1.9%) had mediastinal emphysema without perforation. The rate of accurately diagnosing tumor depth on endoscopic examination was 76.8%. LIMITATIONS: Single-center, nonrandomized study. CONCLUSION: Our study showed that ESD was an effective and relatively safe treatment for superficial esophageal neoplasms. ESD may be a useful treatment option for superficial esophageal neoplasms in hospitals with endoscopists who are experts in performing ESD for gastric tumors. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000002047.).