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Background: Hirschsprung’s Disease (HD) is characterized by intestinal sub-occlusion and the absence of enteric ganglion cells. A rectal biopsy examination is performed to confirm the diagnosis. In a recent study, we demonstrated that the analysis of 60 sections of rectal mucosa and submucosa stained by H&E may ensure a 90% diagnostic accuracy. Although the need to analyze so many sections makes the process of reading the slides more time-consuming, this encouraged us to study their distribution in the healthy rectal submucosa, to simplify the diagnosis. Objectives: To develop a method that facilitates HD diagnosis by studying the distribution of ganglion cells in the submucosal plexus. Methods: Using the calretinin technique, we studied the distribution of plexuses in 60 fragments of rectal submucosa from 19 cadavers. After the study, the reading method created was used for diagnosis in 47 cases of suspected HD, using H&E staining. The accuracy was verified by comparing the results obtained with H&E to those obtained with the acetylcholinesterase technique, the golden standard in our laboratory. Results: The study of submucosal plexus distribution showed that just by examining the submucosal region every 20 µm, approximately, it is possible to locate a ganglionic plexus, and we have already been able to diagnose HD with 93% accuracy. Conclusion: The study of ganglion cell distribution enabled the creation of a simplified method for reading the slides. The method applied achieved good accuracy and it can be used as an alternative method in HD diagnosis.

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes. Biomaterials such as submucosa of small intestine (SIS) have been widely used as patches for bladder repair, but the outcomes are not fully satisfactory. To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization. In this study, we have developed an anti-CD29 antibody-conjugated SIS scaffold (AC-SIS) which is capable of specifically capturing urine-derived stem cells (USCs) in situ for tissue repair and regeneration. The scaffold has exhibited effective capture capacity and sound biocompatibility. In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration. The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.

Idiopathic myointimal hyperplasia of the mesenteric veins is a segmental ischemia associated with noninflammatory hyperplasia of the intimal smooth muscle of the mesenteric veins. Owing to its rarity, timely diagnosis is often difficult.The goal of this study was to improve clinical practice in terms of the diagnosis of idiopathic myointimal hyperplasia of the mesenteric veins.This was a retrospective observational study.This study was conducted in a single institution with case collection from clinical archives.Data from 12 cases of idiopathic myointimal hyperplasia of the mesenteric veins were retrieved from 2006-2020. Most patients were elderly men, with a male-to-female ratio of 10:1.Clinical, endoscopic, radiologic, and pathologic characteristics of idiopathic myointimal hyperplasia of the mesenteric veins served as outcome measures.Radiologically, marked segmental mural thickening and poor enhancement involved the sigmoid colon and rectum in most cases, with extension to the descending colon in some cases. Typical cases showed obliteration of the inferior mesenteric veins and collateral vessels. Colonoscopic findings were reminiscent of ischemia or ulcerative colitis, but sharp demarcation from the uninvolved segment was the most distinguishing feature. Surgically resected specimens showed marked segmental mural thickening, edema, and mucosal discoloration grossly. Microscopically, thick-walled, tortuous veins were observed mainly in the submucosa and subserosa, and the submucosa was markedly thickened in all cases. The subserosal large veins showed myointimal hyperplasia, and pericolic fat necrosis was invariably observed. The most useful histologic finding in biopsy material was tortuous, arteriolized mucosal capillaries with occasional fibrinoid necrosis.This study was limited by its small number of cases and selection bias; there was also no prospective external validation.Radiologic and pathologic features of idiopathic myointimal hyperplasia of the mesenteric veins are distinct from those of ulcerative colitis or nonspecific ischemic colitis. Careful interpretation of endoscopic and radiologic images and generous biopsies with interpretation by experienced pathologists might lead to an early diagnosis and prevent unnecessary medical treatment. See Video Abstract at http://links.lww.com/DCR/B806.ANTECEDENTES:La hiperplasia miointimal idiopática de las venas mesentéricas es una isquemia segmentaria asociada con hiperplasia no inflamatoria del músculo liso de la íntima de las venas mesentéricas. Debido a su rareza, el diagnóstico oportuno suele ser difícil.OBJETIVO:Mejorar la práctica clínica con respecto al diagnóstico de hiperplasia miointimal idiopática de venas mesentéricas.DISEÑO:Estudio observacional retrospectivo.AJUSTES:Institución única, colección de casos de archivos clínicos.PACIENTES:Se recuperaron datos de 12 casos de hiperplasia miointimal idiopática de las venas mesentéricas durante el período 2006-2020. La mayoría de los pacientes eran hombres de edad avanzada, con una proporción de hombres a mujeres de 10:1.PRINCIPALES MEDIDAS DE RESULTADO:Características clínicas, endoscópicas, radiológicas y patológicas de la hiperplasia miointimal idiopática de las venas mesentéricas.RESULTADOS:Radiológicamente, se vio marcado engrosamiento mural afectando de manera segmentaria y escaso realce que comprometieron al colon sigmoides y al recto en la mayoría de los casos, con extensión al colon descendente en algunos casos. Los casos típicos mostraron obliteración de las venas mesentéricas inferiores y vasos colaterales. Los hallazgos colonoscópicos recordaban a la isquemia o la colitis ulcerosa, pero la demarcación nítida del segmento no afectado fue la característica más distintiva. Las piezas quirúrgicas mostraron un marcado engrosamiento mural de manera segmentaria, edema y decoloración de la mucosa de forma macroscópica. Microscópicamente, se observaron venas tortuosas de paredes engrosadas principalmente en la submucosa y subserosa y la submucosa se encontraba marcadamente engrosada en todos los casos. Las grandes venas subserosas mostraban hiperplasia de la mioíntima e invariablemente se observaba necrosis grasa pericólica. El hallazgo histológico más útil en el material de biopsia fueron los tortuosos capilares arteriolizados de la mucosa con necrosis fibrinoide ocasional.LIMITACIONES:Pequeño número de casos; sesgo de selección; sin validación externa prospectiva.CONCLUSIONES:Las características radiológicas y patológicas de la hiperplasia miointimal idiopática de las venas mesentéricas son distintas a las de la colitis ulcerosa o la colitis isquémica no específica. La interpretación cuidadosa de las imágenes endoscópicas y radiológicas y múltiples biopsias de manera generosa con la interpretación de patólogos experimentados pueden conducir a un diagnóstico temprano y prevenir tratamientos médicos innecesarios. Consulte Video Resumen en http://links.lww.com/DCR/B806. (Traducción-Dr Osvaldo Gauto).

Background Barrett's oesophagus (BO) is known precursor of oesophageal adenocarcinoma (EAC). Early EAC includes T1a (invasion into mucosa) and T1b (invasion into submucosa but not muscularis propria). Endoscopic mucosal resection (EMR) provides accurate histological staging and definitive treatment for early EAC. Post EMR, the remaining Barrett's is eradicated with radiofrequency ablation (RFA). However, there is a paucity of long-term Australian data. Aims To investigate the efficacy and long-term outcomes of EMR and RFA in management of early EAC. Methods Retrospective analysis of patients early EAC treated endoscopically at three Western Australian tertiary centres, with at least 12-months follow-up, over last 10-years. Results Sixty-seven patients with early EAC (61 T1a and 6 T1b) were treated with EMR. Complete Barrett's eradication was done by EMR in 31/67 patients whereas 36/67 patients underwent RFA for residual Barrett's. EMR changed pinch biopsy histology from HGD (n=33), HGD suspicious for IMC (n=5) and LGD (n=1) to early EAC in 58.2% (n=39) patients. During a mean follow-up of 37.2 months (IQR 20, 56), complete remission of dysplasia (CRD) and intestinal metaplasia (CRIM) was seen in 97% (n=65) and 89.5% (n=60) patients. One patient with T1b EAC underwent oesophagectomy. No cases developed metachronous EAC, progression to invasive adenocarcinoma or development of nodal/distant metastasis. Complications were endoscopically treated haematemesis (n=1) and strictures (n=16) requiring dilatations. 3 patients died due to causes unrelated to IMC. Conclusion EMR in conjunction with RFA is an effective and safe management for early EAC. EMR provides accurate staging and has low complication rates. This article is protected by copyright. All rights reserved.

The eighth edition of the American Joint Committee on Cancer classifies nonmetastatic, node-negative colorectal cancers invading the submucosa (T1) and muscularis propria (T2) as stage I tumors without additional subclassification.The aim of the study was to compare survival of T1N0M0 versus T2N0M0 colorectal cancers and to investigate factors associated with decreased survival.This was an analysis of 2 large population-based data sets.The study was conducted analyzing data from the Surveillance Epidemiology and End Result program and the National Cancer Database.Adult patients undergoing major resection without additional therapy for stage I colorectal cancer were included.Overall and disease-specific survival for T1 versus T2 cancers were measured. Subgroup analyses by tumor location (colon versus rectum) were performed.A total of 30,228 (36.4% T1 and 63.6% T2) and 41,670 (41.1% T1 and 58.9% T2) patients were identified in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5-year overall survival rates were 87.1% and 86.2% for patients with T1 versus 82.7% and 80.7% for patients with T2 (p0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 10-year overall survival rates were 71.3% and 66.3% for patients with T1 versus 62.2% and 57.2% for patients with T2 tumors (p0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5- and 10-year disease-specific survival for colorectal cancer in the Surveillance Epidemiology and End Result database was 97.0% (T1) versus 95.2% (T2) and 94.1% (T1) versus 90.3% (T2). Black race (HR = 1.26 and 1.65 for overall survival and disease-specific survival in the Surveillance Epidemiology and End Result database; HR = 1.20 for overall survival in the National Cancer Database) was associated with worse survival.The study was limited by intrinsic biases related to large administrative data sets.Within stage I colorectal cancer, T2 tumors have decreased overall survival and disease-specific survival as compared with T1 cancers. This survival difference may justify revising the American Joint Committee on Cancer staging system to include the subclassification of stage Ia (T1N0M0) and stage Ib (T2N0M0). See Video Abstract at http://links.lww.com/DCR/B659.ANTECEDENTES:La octava edición del American Joint Committee on Cancer, clasifica los cánceres colorrectales no metastásicos con ganglios negativos, que invaden la submucosa (T1) y la muscularis propia (T2) como tumores en estadio I sin subclasificación adicional.OBJETIVO:El objetivo del estudio fue comparar la sobrevida de los cánceres colorrectales T1N0M0 versus T2N0M0 e investigar los factores asociados con la disminución de la sobrevida.DISEÑO:Análisis de dos grandes conjuntos de datos poblacionales.MARCO:El estudio se realizó analizando datos del Programa de Epidemiología de Vigilancia y Resultados Finales (SEER) y la Base de Datos Nacional del Cáncer.PACIENTES:Pacientes adultos en los cuales se realizó una resección mayor sin terapia adicional por cáncer colorrectal en estadio I.PRINCIPALES VARIABLES ANALIZADAS:Sobrevida global y específica de la enfermedad para los cánceres T1 versus T2. Se realizó un análisis de subgrupos según la ubicación del tumor (colon versus recto).RESULTADOS:Se incluyeron un total de 30.228 (36,4% T1 y 63,6% T2) y 41.670 (41,1% T1 y 58,9% T2) pacientes en las bases de datos SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 5 años fue del 87,1% y el 86,2% para los pacientes con T1 frente al 82,7% y el 80,7% de los pacientes con T2 (p0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 10 años fue del 71,3% y el 66,3% para los pacientes con T1 frente al 62,2% y el 57,2% de los pacientes con tumores T2 (p0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida específica de la enfermedad a 5 y 10 años para el cáncer colorrectal en el SEER fue del 97,0% (T1) frente al 95,2% (T2) y del 94,1% (T1) frente al 90,3% (T2), respectivamente. La grupo étnico afroamericano se asoció con una sobrevida menor (Hazard Ratio -HR 1,26 y 1,65 para la sobrevida general y sobrevida específica de la enfermedad-SEER; HR 1,20 para la sobrevida general-Base de de Datos Nacional del Cáncer).LIMITACIONES:Sesgos intrínsecos relacionados con el análisis de grandes conjuntos de datos.CONCLUSIONES:Dentro del cáncer colorrectal en estadio I, los tumores T2 han disminuido la sobrevida general y la sobrevida específica de la enfermedad, en comparación con los cánceres T1. Esta diferencia de sobrevida puede justificar la revisión del sistema de estadificación del American Joint Committee on Cancer para incluir la subclasificación del estadio Ia (T1N0M0) y el estadio Ib (T2N0M0). Consulte Video Resumen en http://links.lww.com/DCR/B659.

Enteritis cystica profunda (ECP), a rare and benign condition, is defined as the displacement of the glandular epithelium into the submucosa and more profound layers of the small intestinal wall leading to the formation of mucin-filled cystic spaces. ECP frequently occurs in the ileum or jejunum and is associated with diseases such as Crohn disease and Peutz-Jeghers syndrome. ECP also develops in the absence of known pathology. ECP in the duodenum is very rare and mostly occurs without associated conditions. In this report, we present a rare case of ECP without an associated disease, in the second portion of the duodenum distal to the ampulla of Vater and coexisting with lipoma within the polypoid lesion.

This case series presents three patients with Stage II and III rectal cancer treated with neoadjuvant (chemo)radiotherapy who, after achieving initial complete response, developed cancer regrowths. In over 90% of cases, rectal cancer regrows in the rectal lumen and is primarily detected by digital examination and rectoscopy. In the presented cases, regrowths were detected uniquely with Magnetic Resonance Imaging with the support of Diffusion Weighed Imagingthe rectal submucosa, where they were invisible to other assessment modalities. This article aims to create awareness towards this possible alternative location of rectal cancer regrowths and to the importance of good quality MRI and experienced radiologists in the non-operative management of rectal cancer patients.C

Highlights • PDAC cells in the duodenal epithelium mimic intestinal cells and co-opt the basement membrane. • Intramucosal PDAC location is strongly coupled to the classical phenotype and to intestinal traits. • Intratumoral heterogeneity is linked to specific tissue compartments, which shape phenotype plasticity of PDAC cells., Introduction Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes have been defined that differ in prognosis. Cells of both subtypes can coexist in individual tumors; however, the contribution of either clonal heterogeneity or microenvironmental cues to subtype heterogeneity is unclear. Here, we report the spatial tumor phenotype dynamics in a cohort of patients in whom PDAC infiltrated the duodenal wall, and identify the duodenal epithelium as a distinct PDAC microniche. Materials and methods We used serial multiplex quantitative immunohistochemistry (smq-IHC) for 24 proteins to phenotypically chart PDAC tumor cells in patients whose tumors infiltrated the duodenal epithelium. Additionally, we used a genetically engineered mouse model to study the PDAC cell phenotype in the small intestinal epithelium in a controlled genetic background. Result We show that pancreatic cancer cells revert to non-destructive growth upon integration into the duodenal epithelium, where they adopt traits of intestinal cell differentiation, associated with phenotypical stabilization of the classical subtype. The integrated tumor cells replace epithelial cells in an adenoma-like manner, as opposed to invasive growth in the submucosa. Finally, we show that this phenomenon is shared between species, by confirming duodenal integration and phenotypic switching in a genetic PDAC mouse model. Discussion Our results identify the duodenal epithelium as a distinct PDAC microniche and tightly link microenvironmental cue to cancer transcriptional subtypes. The phenomenon of “intestinal mimicry” provides a unique opportunity for the systematic investigation of microenvironmental influences on pancreatic cancer plasticity.

Geophagus brasiliensis, popularly known as acará, is a common fish in lentic freshwater environments in South America. This species has a detritivorous-iliophagous or omnivorous feeding habit, with high food plasticity; however, there are no studies describing its intestinal tract histologically. Therefore, the present study analysed through histological and histochemical techniques the intestines of the acará. Adult specimens were collected with gillnets, anaesthetized and euthanized. Then, the fish were submitted to biometry and dissection to remove fragments of intestines. The samples were fixed in Bouin liquid for 12 hours and subjected to histological and histochemical techniques. Histologically, all samples of intestines were organized into four layers: mucosa, submucosa, muscular and serosa. The small intestine (foregut and midgut) was characterized by the presence of intestinal villi covered by simple prismatic epithelium with a striated border and goblet cells supported by the connective lamina propria. In the large intestine (hindgut), there was an absence of villi and an abundance of goblet cells. Positive reaction to Periodic Acid-Schiff (PAS) and Alcian Blue (AB) pH 2.5 reactions were detected in goblet cells, indicating the presence of mucosubstances. No lipids were detected in the intestine cells due to the negative reaction to the Sudan Black B. The results of the present study provide subsidies for a better understanding of the intestinal morphology of teleosts and provide valuable information for phylogenetic studies.

Objective To present the pathologic analysis of female urethral strictures obtained during reconstructive urethroplasty. Methods Nine separate female urethral tissue specimens were obtained during dorsal vaginal graft urethroplasty by a single surgeon (S.P.P.). Samples were serially sectioned and fixed in 10% formalin 6 to 12 hours before routine processing in paraffin blocks. Serial 5-µm sections were subjected to H&E, Masson trichrome, and elastin staining. End point analysis included evaluation for epithelial hyperplasia and cell type, mucosal edema, degree of fibroblast/inflammatory cell infiltrate, and elastin fiber density and distribution. Results Nine specimens were examined. Six specimens had epithelial linings of stratified squamous epithelium overlying fibrosis (67%), 1 had mixed squamous and urothelial epithelium, and 2 had only urothelial epithelium. Two specimens (29%) showed acute injury with prominent squamous papillary hyperplasia, focal erosion, and patchy mucosal hemorrhage. Areas of urethral stricture were variably thickened, with increased, densely packed collagen fibers and associated mucosal lymphocytic inflammation ranging from mild and patchy to focally dense with lymphoid aggregates. The highest elastin fiber density appeared to be associated with vessels and overlying muscle bundles in the submucosa. Conclusions Further elucidation of histopathologic characteristics may illuminate more appropriate therapeutic pathways for female urethral stricture disease management.

OBJECTIVES Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited. METHODS Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months). RESULTS In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively. CONCLUSIONS Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated.

Background Appendiceal neurendocrine tumours (NETs) are rare neoplasms and diagnosis is commonly incidental following appendectomy. We aimed to review our experience with appendiceal NETs. Methods Records of children with appendiceal NETs were reviewed and data concerning demographic characteristics, clinical findings, surgical procedures, histopathological findings, management and outcomes were recorded. Results Between 1985 and 2021, 33 cases with appendiceal NETs (median age 11.8 years, range 7.8-16; male/female = 10/23) were identified. All but one patients presented with abdominal pain, six had vomiting, four had fever and they underwent appendectomies with presumed diagnosis of acute appendicitis. Abscess drainage and appendectomy was performed in a 16-year-old girl for suspected right ovarian mass, and tumour was positive in the omentum. Histopathological diagnosis was classical carcinoid tumour (NET) in all cases. Median tumour size was 0.9 cm (n = 26, range, 0.1-3.5 cm); tumours were ≤1 cm in 19 cases, 2 cm in one, 3.5 cm in another case. Tumours were located in the tip (n = 11), body (n = 6) and base of appendix (n = 1) (in others data unavailable). In 28 patients with data, tumour extended to submucosa in five, to tunica muscularis in seven, to subserosa in six, to serosa in six, to mesoappendix in three, to periappendiceal fat in one. Three cases were lost to follow-up, 31 cases were alive (median follow-up 53 months). Conclusions Paediatric appendiceal NETs do not behave aggressively and appendectomy alone is sufficient for tumours ≤2 cm regardless of local invasion. The need for further extensive surgery in tumours >2 cm also remains controversial.

BACKGROUND Accurate diagnosis of the depth of gastric cancer invasion is crucial in clinical practice. The diagnosis of gastric cancer depth is often made using endoscopic characteristics of the tumor and its margins; however, evaluating invasion depth based on endoscopic background gastritis remains unclear. AIM To investigate predicting submucosal invasion using the endoscopy-based Kyoto classification of gastritis. METHODS Patients with gastric cancer detected on esophagogastroduodenoscopy at Toyoshima Endoscopy Clinic were enrolled. We analyzed the effects of patient and tumor characteristics, including age, sex, body mass index, surveillance endoscopy within 2 years, current Helicobacter pylori infection, the Kyoto classification, and Lauren's tumor type, on submucosal tumor invasion and curative endoscopic resection. The Kyoto classification included atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. Atrophy was characterized by non-reddish and low mucosa. Intestinal metaplasia was detected as patchy whitish or grayish-white flat elevations, forming an irregular uneven surface. An enlarged fold referred to a fold width ≥ 5 mm in the greater curvature of the corpus. Nodularity was characterized by goosebump-like multiple nodules in the antrum. Diffuse redness was characterized by uniform reddish non-atrophic mucosa in the greater curvature of the corpus. RESULTS A total of 266 gastric cancer patients (mean age, 66.7 years; male sex, 58.6%; mean body mass index, 22.8 kg/m2) were enrolled. Ninety-three patients underwent esophagogastroduodenoscopy for surveillance within 2 years, and 140 had current Helicobacter pylori infection. The mean Kyoto score was 4.54. Fifty-eight cancers were diffuse-type, and 87 cancers had invaded the submucosa. Multivariate analysis revealed that low body mass index (odds ratio 0.88, P = 0.02), no surveillance esophagogastroduodenoscopy within 2 years (odds ratio 0.15, P < 0.001), endoscopic enlarged folds of gastritis (odds ratio 3.39, P = 0.001), and Lauren's diffuse-type (odds ratio 5.09, P < 0.001) were independently associated with submucosal invasion. Similar results were obtained with curative endoscopic resection. Among cancer patients with enlarged folds, severely enlarged folds (width ≥ 10 mm) were more related to submucosal invasion than mildly enlarged folds (width 5-9 mm, P < 0.001). CONCLUSION Enlarged folds of gastritis were associated with submucosal invasion. Endoscopic observation of background gastritis as well as the lesion itself may help diagnose the depth of cancer invasion.

Secondary amyloidosis is a rare complication of chronic inflammatory diseases, such as collagen diseases, and is often difficult to treat. In addition, the gastrointestinal tract is frequently involved in amyloid deposition that often results in various disorders and symptoms. A 70-year-old woman was admitted to our hospital with refractory diarrhea and hypoalbuminemia. Abdominal computed tomography demonstrated extensive edematous wall thickening of the small intestine and colon. Video capsule endoscopy revealed multiple ulcerations with a white mossy appearance of the ileum. Double-balloon endoscopy showed severe circumferential ulcers in the entire ileum. Histological examination of ileum biopsy samples revealed severe amyloid deposition in the lamina propria and perivascular areas of the submucosa. The patient was diagnosed with gastrointestinal AA amyloidosis. The cause of AA amyloid deposition was presumed to be chronic pyelonephritis due to ureteral stones that had been left untreated for 35 years. After treatment with ureteral drainage and antibiotics, the patient's symptoms and serological abnormalities improved dramatically. Here, we describe a case of severe gastrointestinal AA amyloidosis secondary to chronic pyelonephritis. Clinicians should thoroughly investigate the entire gastrointestinal tract in patients with refractory diarrhea and severe hypoalbuminemia considering the possibility of gastrointestinal amyloidosis.

Background Pedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis. Case presentation A 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 μm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery. Conclusions Additional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.

This study investigated the histomorphological, ultrastructural and morphometrical postnatal developmental changes in the rabbit fundic region, especially during changing of the feeding intake. Seventy-two New Zealand rabbits (V-Line breed) at the ages of 1, 7, 15, 23, 30 and 60 days were obtained for light and electron microscopy and morphometric studies of the fundic region. The newborn rabbit's fundic wall was thin and organized into mucosa, submucosa, musclosa and serosa, with a significant increase in thickness with ageing. The fundic glands were few at the first week of life, then increased in length and diameter compared to the preceding age with prominent zonation at 23 days. The gastric pits appeared wide and deep at the first week of life then became typically narrow and shallow at the third week. The mucous cells were the main cell types lining the fundic glands in the first week of life. These cells showed remoulding with a marked increase in Periodic Acid-Schiff reactivity with age. Parietal cells were differentiated earlier (on the first day of life) than the chief cells and distributed at the neck and basal zones. Chief cells differentiated at 15 days old at the base of the glands, followed by an increase in the number and activity. Few active enteroendocrine cells were first seen at 15 days old and then widely distributed throughout the glands. Conclusion: Pronounced histomorphological changes in the fundic mucosal layer, especially the surface and glandular epithelium, correlate with the postnatal rabbit-feeding intake changes.

Endoscopic resection (ER) is performed for early esophageal squamous cell carcinoma (ESCC) cases. Additional esophagectomy or chemoradiotherapy is recommended for non-curative resection (NCR) even with pathologically negative vertical margins (pVM0); however, their clinical outcomes remain unknown. We examined the long-term clinical outcomes of NCR for ESCCs according to additional treatments.We retrospectively analyzed the data of patients who underwent ER for cT1N0M0 ESCC between 2009 and 2017 judged to have NCR, which defined when pathologically diagnosed as invading the submucosa (SM) or muscularis mucosae (MM) involving lymphovascular invasion (LVI), pVM0, and endoscopically judged as negative horizontal margin. Additional esophagectomy (involving three-field lymphadenectomy), chemoradiotherapy [mainly cisplatin and 5-fluorouracil with concurrent radiotherapy (41.4 Gy)], or observation was undertaken. Thereafter, computed tomography was performed every 6-12 months. The cumulative recurrence (CRR) and recurrence-free survival (RFS) rates were evaluated.Eighty-nine patients were included. Among them, 14 had pathologically diagnosed pMM with LVI; 9 and 6, and 32 and 28 patients had pSM1 and pSM2 without and with LVI. Twenty-one patients underwent observation, whereas 18 and 50 underwent esophagectomy and chemoradiotherapy. During the 60.6-month median follow-up period, nine patients had recurrence; among them, six patients had occurrence at 4 years after ER. The 5-year CRR/RFS rates were 35.7%/48.1%, 13.4%/80.4%, and 0.0%/98.0% in the observation, esophagectomy, and chemoradiotherapy groups, respectively (observation vs. chemoradiotherapy; P 0.001).Additional treatments showed better long-term outcomes than observation for patients with NCR. As recurrence may occur at 4 years after ER, careful long-term follow-up examinations are needed.

NUTM1 gene rearrangements were originally identified in NUT carcinoma. Recently, NUTM1 has been discovered to rearrange with a variety of gene partners in malignancies of diverse location and type. Only one NUTM1-rearranged tumor occurring in the colon has been reported. Herein we report five such tumors. The five tumors occurred in four females and one male, ranging from 38 to 67 years of age (median 51 years). The masses occurred in the colon (cecum, descending, sigmoid) and ileocecal valve region, measuring 2.5-20 cm in size (median 7 cm). Four patients had metastases at presentation (liver, n = 4; lymph nodes, n = 3). Histologically, the lesions arose in the submucosa, infiltrating into the mucosa and muscularis propria, and grew in fibrosarcoma-like fascicles and sheets of epithelioid or rhabdoid cells, with foci of hyalinized to vaguely osteoid-like matrix. The tumors were composed of relatively monomorphic, spindled to epithelioid cells with focal rhabdoid morphology, hyperchromatic nuclei, and small nucleoli. Mitotic activity was usually low (range 1-14/10 HPF; median 5/10 HPF); necrosis was present in two cases. Variable keratin expression and uniform nuclear NUT expression was present; KIT/DOG1 were negative and SMARCB1/SMARCA4 were retained. Next-generation sequencing identified MXD4-NUTM1 rearrangement in all cases (breakpoints: MXD4 exon 5, NUTM1 exons 2 or 3). Follow-up showed one of the four patients who presented with metastases to be dead of disease at 30 months; the other three patients were alive with metastatic disease. The final patient is disease-free, 5 months after diagnosis. NUTM1-rearranged colorectal sarcomas have characteristic morphologic, immunohistochemical, and molecular genetic features, suggesting that they represent a distinct entity within the family of NUTM1-rearranged neoplasia. A NUTM1-rearranged tumor should be considered for any difficult-to-classify submucosal spindle cell neoplasm of the gastrointestinal tract, in particular keratin-positive tumors showing an unusual combination of fibrosarcomatous, epithelioid to rhabdoid and hyalinized morphologies. Recognition of MXD4-NUTM1 rearranged sarcomas may be therapeutically important, even though best treatment is currently elusive/unknown.

Background Esophageal achalasia causes dysphagia following impaired relaxation of the lower esophageal sphincter due to the degeneration of Auerbach’s plexus in the esophageal smooth muscle. Recently, peroral endoscopic myotomy (POEM) has become one of the preferred treatment options for esophageal achalasia. However, pathomorphological changes after POEM have not been well examined. Case presentation A 65-year-old man with a history of POEM for esophageal achalasia was diagnosed with clinical stage II (cT2-N0-M0) thoracic esophageal squamous cell carcinoma and was consequently treated with neoadjuvant chemotherapy followed by thoracoscopic esophagectomy. Intraoperatively, the esophagus appeared dilated, reflecting esophageal achalasia; however, fairly slight fibrous adhesions were observed between the esophagus and the pericardial surface despite previously performed POEM via an anterior incision. Histopathological examination revealed esophageal wall thickening, edema, and fibrosis extending from the lamina propria to the submucosa. Besides, the majority of the inner layer and some proportion of the outer layer of the muscularis propria were found to be missing or atrophic at the esophagogastric junction (EGJ). No ganglion cells could be detected at the Auerbach’s plexus. Conclusions The previous history of POEM did not affect circumferential mediastinal periesophageal dissection during thoracoscopic esophagectomy. Nevertheless, a large proportion of the inner layer of the muscularis propria at the EGJ level seemed to have become lost or atrophic because of the POEM procedure.

The gene of A-kinase anchor protein 12 (AKAP12) regulates cell cycle progression, cell motility, and morphology through its multiple scaffolding domains. However, the role of AKAP12 expression in ulcerative colitis (UC) patients has not been yet described. The aim of the study was to describe the gene and protein of AKAP12 expression in patients with UC and its association regarding the disease severity. We included a total of 40 patients with confirmed diagnosis of UC and 25 controls without endoscopic evidence of colitis or neoplasia. The relative quantification of the gene expression was performed by real-time PCR for AKAP12. Kruskal–Wallis was used to test differences among groups, and Spearman correlation to assess the relationship between AKAP12 gene and clinical outcomes. The extent of disease was evaluated using total colonoscopy, and biopsies were taken from rectum segments. The AKAP12 gene expression was increased in colonic mucosa from patients with active UC when compared with UC remission and control group. The overexpression of AKAP12 in patients with UC was associated with the presence of extensive colitis (p = 0.04, RM = 12, IC = 1.29–186.37). AKAP12/CD16 double positive cells were higher in submucosa (p = 0.04), muscular (p