Lamina Muscularis Mucosae Research Articles

The association between variant histology and prognostic, histomorphological and clinical aspects of bladder urothelial carcinoma

This study underscores the imperative consideration of histological subtypes and divergent differentiation in accurately estimating bladder urothelial carcinoma prognosis and guiding treatment decisions. A comparative analysis was conducted, examining clinical, histological, and prognostic factors between conventional urothelial carcinoma and urothelial carcinoma with variant histology in a clinical sample. A retrospective analysis of slides and other clinicopathologic data was conducted these cases, with an emphasis on key diagnostic elements. We examined 829 cases of urothelial carcinoma of the bladder, comprising of 744 transurethral resection (TUR) and 85 radical cystectomy (RS) specimens, an analysis that showed that 80.5 % (667 cases) were conventional urothelial carcinoma (CUC) and that 19.5 % (162 cases) exhibited variant histology (hereafter “urothelial carcinoma with subtype histology” [UCSH]). TNM classifications for the RS cases were as follows: 2 cases were stage group 0a, 11 stage group 1, 16 stage group 2, 45 stage group 3a, 2 stage group 3b, 1 stage group 4a, and 8 stage group 4b. Only 2 of the RS cases were found to be non-invasive. Among 744 TUR specimens, 387 were found to have a non-invasive tumor whereas 357 had invasive tumors. The most prevalent subtype in the UCSH group was urothelial carcinoma with squamous differentiation, accounting for 54.3 % (88 cases). Notably, 8.02 % (13 cases) exhibited more than one histological subtype. Papillary configuration, histological grade, lamina propria, muscularis mucosa and serosa invasion, lymphovascular invasion, presence of urothelial carcinoma in situ, and overall survival significantly differed between the UCSH and CUC groups (p < 0.05). However, mean age, gender, tumor size, lymphocytic response, disease-free survival, and survival status did not differ significantly (p > 0.05). Among the UCSH group, lower levels of papillary configuration, higher histological grade, higher degree of lamina propria, muscularis mucosa and serosa invasion, and the presence of carcinoma in situ corresponded to higher percentage of histological subtype morphology (p < 0.05). No significant difference in survival status was observed between the groups with and without subtype histology (p = 0.083). This study found that clinical and histopathological prognostic factors associated with a more aggressive disease were linked to the presence and percentage of histological subtypes. Recognizing histological subtype is crucial for treatment decisions and prognosis prediction in urothelial carcinoma cases with these subtypes.

The Japanese Esophageal Society classification for prediction of superficial esophageal squamous cell neoplasia invasion depth: Validation in a Western population.

The Japan Esophageal Society proposed the JES microvessel classification to assess eligibility of early esophageal squamous cell neoplasia (ESCN) for endoscopic resection based on intrapapillary capillary loop assessment. We aimed to assess its diagnostic reproducibility and accuracy in Western ESCN patients. Intrapapillary capillary loops on endoscopic images of Western ESCN lesions (n=113) collected between 2010 and 2022 were assessed by nine endoscopists, including three Japanese expert endoscopists, three Western expert endoscopists, and three residents-in-training, and graded according to the JES microvessel classification where microvessel type A corresponds with normality or low-grade intraepithelial neoplasia, and microvessel types B1, B2, and B3 correspond with high-grade intraepithelial neoplasia or invasion into the lamina propria, muscularis mucosae or superficial submucosa, and deep submucosa, respectively. Outcomes included overall accuracy in predicting ESCN invasion depth and interobserver agreement. Good interobserver agreement was observed among expert endoscopists (Krippendorf's alpha 0.64, 95% CI 0.57-0.70), while agreement was moderate among residents-in-training (Krippendorf's alpha 0.58, 95% CI 0.52-0.72). Overall accuracy of the JES microvessel classification was 53% (95% CI 42-63), 52% (95% CI 41-62), and 44% (95% CI 34-55) for Japanese endoscopists, Western endoscopists, and residents-in-training, respectively. Sensitivity and specificity for vessel type A, B1, B2, and B3 across assessors were 0%-50% and 89%-100%, 55%-64% and 66%-77%, 42%-71% and 60%-76%, and 10%-24% and 92%-97%, respectively. Negative predictive value ranged between 80% and 85% for B3 vessels. Overall accuracy of the JES microvessel classification in Western ESCN patients is low, though absence of B3 vessels as assessed by experienced endoscopists may predict superficial ESCN amenable to endoscopic resection. www.trialregister.nl; NL8897 (6-9-2020).

Characterization of early-stage lesions and investigation on the role of mucosal trauma in hemorrhagic bowel syndrome in cattle

Hemorrhagic bowel syndrome (HBS) is characterized by a dissecting intramucosal hematoma at the small bowel, causing obstruction and severe hemorrhage in dairy cattle. Recent investigation revealed the presence of early-stage lesions in cows affected by HBS. These are presumed to be the initial stage of the hematoma, as both share unique dissection of the lamina muscularis mucosae (LMM) as histological hallmark. Early-stage lesions of HBS have not been characterized in greater detail, and neither has the hypothesis of mucosal abrasion as etiology been explored. Therefore, the first objective of the present study was to characterize the morphology of early-stage lesions, by gross examination, histochemistry, immunohistochemistry and transmission electron microscopy. The second objective was to determine the effect of mucosal abrasion to the small intestine in an ex vivo model. A total of 86 early-stage lesions from 10 cows with HBS were characterized. No underlying alterations at the LMM were evident which could explain their occurrence. However, degeneration at the ultrastructural level of the LMM smooth muscle cells was present in 3 of 4 lesions, it is however unclear whether this is primary or secondary. Bacteriological examination did not reveal any association with a specific bacterium. Experimental-induced and early-stage lesions were gross and histologically evaluated and scored in three cows with HBS and seven controls. Experimentally induced lesions in both affected cows and controls, were histologically very similar to the naturally occurring early-stage lesions. Altogether, the results are suggestive for mucosal trauma to play a role in the pathogenesis of HBS.

Leiomyosarcoma of the esophagus, arising from lamina muscularis mucosae, in a combination with microinvasive squamous cell carcinoma-A case report.

Leiomyosarcoma of the esophagus is a very rare disease, accounting for less than 0.5% of malignant esophageal tumors. Esophageal leiomyosarcoma combined with squamous cell carcinoma is even rarer than solitary leiomyosarcoma. To our knowledge, there are less than ten cases of simultaneously diagnosed leiomyosarcoma and squamous cell carcinoma of the esophagus. A 66-year-old male was admitted to our hospital suffering from epigastric pain, asthenia, weight loss, and difficulties when feeding with solid food which had been present for 2 weeks. A computed tomography scan showed a large tumor tissue mass in the mid-to-distal part of the esophagus. The patient underwent robot-assisted surgery-an esophagectomy with esophagogastrostomy. Histologically, the tumor consisted of highly pleomorphic spindle cells with multiple atypical mitosis and necrotic areas. An immunohistochemical examination was performed to distinguish leiomyosarcoma from spindle cell squamous carcinoma or malignant GIST. Tumor cells stained diffusely positive for smooth muscle actin, but negative for p63, CD117, and CKAE1/AE3. Tumor invasion involved mucosa and submucosa, without tunica muscularis propria. Microinvasive well-differentiated squamous cell carcinoma was also noted in the mucosa at the borders between the tumor and the healthy part of the esophagus. The aim of the manuscript is to present an extremely rare case of combined polypoid leiomyosarcoma and microinvasive squamous cell carcinoma of the esophagus, cured by robot-assisted surgical intervention and to emphasize that such cases should be examined carefully, including additional diagnostic tests such as Immunohistochemistry (IHC) in order to define the correct diagnosis.

Kajian Histokimia Sebaran Karbohidrat Netral Pada Usus Halus Ayam Hutan Hijau (Gallus Varius) Asal Pulau Alor

Green jungle fowl (Gallus varius) is a type of local chicken in Indonesia. Green jungle fowl are only found in Indonesia, which are spread from Java, Madura, Bali, Lombok, Sumba, Sumbawa, Flores and Alor. The small intestine consists of the duodenum, jejunum and ileum which function in the absorption of nutrients. Periodic Acid Schiff (PAS) is a special staining method that aims to see the characteristics of neutral carbohydrates in cells or body tissues. A positive PAS staining reaction is indicated by the presence of a magenta-red color in the examined tissue. This study aims to determine the distribution of neutral carbohydrates in the small intestine of the green jungle fowl (Gallus varius) from Alor Island. Small intestine samples were taken from 3 green jungle fowl collected in Alor District. Microscopic observation of small intestine tissue that has been stained with PAS stain. The results showed that the small intestine of the green jungle fowl consists of the duodenum, jejunum and ileum. Neutral carbohydrates are distributed throughout the tunica duodenum, jejunum and ileum with varying intensity. Moderate intensity (++) was seen in goblet cells and liberkuhn's crypts. Weak intensity (+) is seen on the surface of the epithelium, lamina propria, lamina muscularis mucosa, tunica submucosa, tunica muscularis, and tunica serosa.

A152 THE RISK OF UNFAVORABLE HISTOLOGIC FEATURES, LYMPH NODE METASTASIS AND METACHRONOUS ADVANCED NEOPLASIA IN PATIENTS WITH COLORECTAL INTRAMUCOSAL CARCINOMA

Abstract Background Very few studies have described the risk of unfavorable histologic features (UHFs), lymph node involvement (LNI), distant metastasis (DM) and metachronous advanced neoplasia (MAN) after the detection of colorectal intramucosal carcinoma (IMC). Aims This study aimed to determine the risk of UHFs, LNI, DM and MAN in patients with IMC, compared to high-grade dysplasia (HGD) or T1 colorectal cancer (CRC). Methods A retrospective cohort study was conducted. Through a pathology database search, we identified all consecutive patients with HGD (epithelial) (n=908) or either IMC (lamina propria or muscularis mucosa) or T1 CRC (submucosa) (n=496) diagnosed between 2010 and 2019 at the University of Montreal Hospital Center. We excluded patients with age ampersand:003C40 or ampersand:003E90, IBD, hereditary CRC or post-neoadjuvant therapy. Primary outcome was the risk of UHF, LNI and DM in IMC vs T1. Secondary outcome was the risk of MAN (metachronous advanced adenoma or advanced serrated lesion or CRC) in the IMC group, compared to HGD and T1. Files were reviewed for demographics and index and follow-up findings. The metachronous analysis excluded follow-ups ampersand:003C6 months, no follow-up or previous CRC. Follow-up continued until MAN or last colonoscopy within 10 y. Variables were compared between groups using ANOVA, chi-squared tests or Kruskal-Wallis tests, followed by post-hoc tests. We performed multivariate Cox regressions, adjusting for age, sex, family history of CRC, main lesion location, villous histology, adenomas ≥10 mm, and number of adenomas. Results The primary cohort included 90 patients with IMC (mean age 69.4 y., 44.4% female) and 207 with T1 CRC (mean age 69.8 y., 43.5% female), as well as 797 with HGD. The rates of lymphatic invasion, vascular invasion, intermediate differentiation/grade and mucinous histology were 2/90, 1/90, 7/90 and 4/90 in the IMC group compared to respectively 30/207 (2.2% vs 14.5%, pampersand:003C0.01), 15/207 (1.1% vs 7.2%, p=0.06), 68/207 (7.7% vs 32.9%, pampersand:003C0.01) and 15/207 in the T1 group (4.4% vs 7.2%, p=0.52). No other UHFs were present. No patients with IMC had LNI or DM. In the metachronous outcomes analysis, 464 patients were eligible (mean age 67.1 y., 42.2% female, median follow-up 3.0 y.): 274 with HGD, 58 with IMC and 132 with T1 CRC. Compared to HGD, patients with IMC had a lower likelihood of MAN (HR 0.46, 0.22-0.96), and T1 CRC had a similar likelihood of MAN (HR 0.65, 0.41-1.02). Compared to IMC, T1 CRC had a similar likelihood of MAN (HR 1.39, 0.63-3.09). Conclusions Patients with colorectal IMC have a small risk of UHFs, but LNI and DM were not identified in this cohort study and have not been reported. Patients with IMC and T1 CRC do not have an increased risk of MAN compared to patients with HGD. Funding Agencies None

Modeling of culture conditions by culture system, glucose and propionic acid and their impact on metabolic profile in IPEC-J2.

The microbiological environment and their corresponding secreted metabolite spectrum are an essential modulator of the enterocyte function, effecting the whole organism. Intestinal porcine jejunal epithelial cell line (IPEC-J2) is an established in vitro model for differentiation of enterocytes in different cell culture models. An improved oxygen supply seems to be the main reason for differentiation in an air-liquid-interface culture, but this has not yet been conclusively clarified. In this context, the nutrition of the cell and its influence on the metabolism is also of crucial importance. The interest in short-chain fatty acids (SCFAs) has grown steadily in recent years due to their clinical relevance in certain diseases such as multiple sclerosis and other inflammatory diseases, but not much is known of FFAR2 and FFAR3 (free fatty acid receptor 2 and 3) in pigs. We want to address the questions: 1. about the distribution of FFAR2 and FFAR3 in vivo and in vitro in sus scrofa 2. whether there is an influence of propionic acid, glucose content and cultivation on metabolism of enterocytes? The morphological analysis of FFAR2 and FFAR3 in vivo was investigated through immunostaining of frozen sections of the porcine gut segments jejunum, ileum and colon. Both receptors are expressed along the gut and were found in the smooth muscle cells of the tunica muscularis and lamina muscularis mucosae. Furthermore, a high expression of FFAR2 and a low expression of FFAR3 in the enteric nerve system was also observed in jejunum, ileum and colon of sus scrofa. In addition, FFAR2 and FFAR3 within the vessels was investigated. FFAR3 showed a strong expression on endothelial cells of veins and lymphatic vessels but was not detectable on arteries. Furthermore, we demonstrate for the first time, FFAR2 and FFAR3 in IPEC-J2 cells on RNA- and protein level, as well as with confocal microscopy. In addition, ENO1 and NDUFA4 were investigated on RNA-level in IPEC-J2 cells as 2 important genes, which play an essential role in metabolism. Here, NDUFA4 is detected in the model animal sus scrofa as well as in the porcine cell line IPEC-J2. A potential impact of propionic acid and/or glucose and/or cultivation method on the metabolism of the cells was tested with the Seahorse analyzer. Here, a significant higher ECAR was observed in the SMC than in the OCR. In summary, we were able to show that the cultivation system appears to have a greater influence than the medium composition or nutrition of the cells. However, this can be modulated by incubation time or combination of different SCFAs.

Quantitative Analysis of NKX2-3 Expression in Human Colon: An Immunohistochemical Study.

In mice, Nkx2-3 homeodomain transcription factor defines the vascular specification of secondary and tertiary lymphoid tissues of the intestines. In human studies, polymorphisms in NKX2-3 have been identified as a susceptibility factor in inflammatory bowel diseases, whereas in mice, its absence is associated with protection against experimental colitis and enhanced intestinal epithelial proliferation. Here, we investigated the expression of NKX2-3 in normal, polyp, and adenocarcinoma human colon samples using immunohistochemistry and quantitative morphometry, correlating its expression with endothelial and mesenchymal stromal markers. Our results revealed that the expression of NKX2-3 is regionally confined to the lamina propria and lamina muscularis mucosae, and its production is restricted mostly to endothelial cells and smooth muscle cells with variable co-expression of CD34, alpha smooth muscle antigen (αSMA), and vascular adhesion protein-1 (VAP-1). The frequency of NKX2-3-positive cells and intensity of expression correlated inversely with aging. Furthermore, in most colorectal carcinoma samples, we observed a significant reduction of NKX2-3 expression. These findings indicate that the NKX2-3 transcription factor is produced by both endothelial and non-endothelial tissue constituents in the colon, and its expression changes during aging and in colorectal malignancies. (J Histochem Cytochem XX: XXX-XXX, XXXX).

Morphological studies on the prehatching development of the glandular stomach of Japanese quails using light, electron, and fluorescent microscopy

The development of the glandular stomach was studied using light, electron, and fluorescent microscopy. The research used 130 Japanese quail eggs from the second to the seventeenth days of incubation.The proventriculus could be distinguished on the3rd day. Its wall consisted of four tunics: tunica mucosa, very thin tunica submucosa, tunica muscularis, and outermost tunica serosa. Mucosal folds appeared on the 8th day. The luminal epithelium was pseudostratified columnar in type and transformed into simple columnar by the 10th day. The mucosal papillae emerged on the 11th day, spiraled on the 15th day, and had a distinct whorled look by the 17th day. Two types of proventricular glands were recognized: compound tubuloalveolar and simple tubular glands. Both types were situated within the tunica mucosa. On the 4th day, the compound glands emerged as evaginations of the lining epithelium. It began to branch on the 8th day and became well established by the 11th day. The simple glands appeared on the 11th day as localized down-growths of the luminal epithelium forming solid cords. On the 15th day, many of them showed complete canalization. On the 8th day, the muscular coat was differentiated into the lamina muscularis mucosae and tunica muscularis.

Copy-number-gain of telomerase reverse transcriptase (hTERT) is associated with an unfavorable prognosis in esophageal adenocarcinoma

Esophageal adenocarcinoma exhibits one of the highest mortality rates among all cancer entities. Multimodal therapy strategies have improved patients’ survival significantly. However, patients in early stages are currently limited to receiving only local therapies, even though some patients within this group showcase short survival periods. Until now, there has been no widely established clinically used biomarker to detect these high-risk patients. Telomerase reverse transcriptase (TERT), a gene encoding a crucial subunit of the telomerase enzyme, plays a significant role in establishing cancer cell immortality and is under suspicion for its potential contribution to tumor progression. Therefore, we aimed to evaluate the clinical relevance of the TERT amplification status. We included 643 patients with esophageal adenocarcinoma, who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. The TERT amplification status was characterized using fluorescence in situ hybridization. Clinicopathological values and patients’ overall survival were compared between patients with and without TERT amplification. Further sub-cohort analyses were conducted for patients with pT1N0-3 tumor stage. Eighty-One patients (12.6%) exhibited TERT amplification. Patients with amplified TERT showed significantly worse overall survival (median OS: 22.6 vs. 36.8 months, p = 0.009). Interestingly, TERT amplification could be characterized as an independent risk factor for worse overall survival in multivariate analysis in patients with pT1N0-3 tumor stage (HR = 2.440, 95% CI 1.095–5.440, p = 0.029). In this study, we describe the TERT amplification status as an independent risk factor for worse survival in patients diagnosed with esophageal adenocarcinoma at pT1N0-3 tumor stage, encompassing cases involving tumor infiltration of the lamina propria, muscularis mucosae, and/or submucosa. Based on our findings, we put forth the proposition that evaluating the TERT amplification status may serve as a valuable tool in identifying a specific subgroup of patients, namely those with TERT amplification and pT1N0-3 tumor-stage esophageal adenocarcinoma. The patients of this subgroup could potentially benefit from enhanced follow-up protocols, more aggressive treatment approaches, or possible targeted TERT inhibition therapies, all aimed at improving their overall clinical outcomes.

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.

An Unexpected Esophageal Lesion in a Patient With Muir-Torre Syndrome

Question: In a 52-year-old female patient with a history of sebaceous gland neoplasms of the skin (carcinoma resected in 2017 and several subsequent adenomas) and positive family history for early-onset colorectal cancer (father at the age of 39 years), Muir-Torre syndrome was suspected. This is a rare variant of Lynch syndrome (LS; approximately 10% of individuals with LS) clinically defined by the typical LS tumor spectrum (colorectal cancer as well as extracolonic tumors, eg, endomtetrial/ovarian cancer, urinary tract cancer) and additional increased risk for characteristic skin neoplasms (especially sebaceous gland neoplasms and keratoacanthoma). DNA mismatch-repair (MMR) deficiency resulting in an accumulation of somatic mutations throughout the genome, also affecting genes involved in carcinogenesis, causes LS. Genetic testing identified a pathogenic germline mutation in MSH2 (mutS homolog 2) on chromosome 2p21 and confirmed the diagnosis in 2018. Compliant with current international guidelines, the patient was included in a specific tumor-screening program. In dermatologic follow-up examinations, basal cell carcinoma and squamous cell carcinoma of the skin were detected. By annual surveillance colonoscopies up to the present, 4 colorectal adenomas with sizes from 2 to 15 mm were resected. On an individual basis, and not covered by guidelines, we performed yearly surveillance esophagogastroduodenoscopy (EGD). Interestingly, at the age of 57 years, a small irregular and slightly elevated lesion (8 mm) with small central erosion (Figure A, arrow) was observed (Paris 0-IIa) in the mid-esophagus (25 cm from incisors). The central part of the lesion stained negative during chromoendoscopy with Lugol’s iodine (1%) (Figure B, arrow) and showed an irregular surface pattern with virtual chromoendoscopy (NBI mode; narrow band imaging) (Figure C). Therefore, malignancy was suspected, and the lesion was removed en bloc by means of rubber-band ligation assisted endoscopic mucosal resection (Figures D and E). Of note, the patient was never a smoker and only occasionally consumed alcohol. Endoscopies were performed with Olympus GIF-H190 endoscopes (Olympus, Hamburg, Germany). Which diagnosis do you suspect and is this lesion LS associated? Look on page 189 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Histopathologic and immunohistochemical examination of the resected tumor revealed poorly differentiated invasive squamous cell carcinoma (pT1a, Pn0, V0, R0, G3) (Figure F, hematoxylin and eosin [HE] stain, ×40) with focal invasion of the lamina muscularis mucosae (Figure G, HE, ×200, arrow). Molecular microsatellite instability testing discovered instability in 4/5 markers (BAT-26, NR-21, BAT-25, and NR-24; NR-27 was stable). When an LS-associated tumor was suspected, MMR protein immunohistochemistry showed a loss of MSH2 expression within the neoplastic cells (Figure H, ×200, red arrow) while surrounding tissue stained positive for MSH2 (Figure H, black arrow) and MLH1 expression was unaffected in neoplastic (Figure I, ×200, red arrow) and nonneoplastic (Figure I, black arrow) cells. Computed tomography and endoscopic ultrasound did not find any distant or lymph-node metastases, and there was no residual tumor in a follow-up endoscopy. Because of poor tumor differentiation and invasion of the lamina muscularis mucosae (m3), additive radiotherapy (50.4 Gy/59.92 Gy boost in 28 fractions) was recommended after discussion by the tumor board. This is the first description of an LS/Muir-Torre syndrome–associated squamous cell carcinoma of the esophagus in a patient without typical risk factors for this tumor entity. Moreover, we show in-depth molecular characterization to prove LS association. Only rarely have adenocarcinomas of the esophagus been reported1Sweetser S. Chandan V.S. Baron T.H. Dysphagia in Lynch syndrome.Gastroenterology. 2013; 145: 1167-1168Abstract Full Text Full Text PDF Scopus (6) Google Scholar in LS. Until recently, squamous cell carcinoma of the skin was not counted as typical skin manifestation of Muir-Torre syndrome, but an association has been demonstrated.2Ykema B.L.M. Adan F. Crijns M.B. et al.Cutaneous squamous cell carcinoma is associated with Lynch syndrome: widening the spectrum of Lynch syndrome-associated tumours.Br J Dermatol. 2021; 185: 462-463Crossref PubMed Scopus (7) Google Scholar Of note, our patient also suffered from squamous cell carcinoma of the skin. In conclusion, clinicians should carefully consider esophageal neoplasms as a rare manifestation of LS. Despite limited data supporting EGD surveillance in LS and in contrast to current guidelines, upper endoscopy could be easily performed along with routine colonoscopy in an effort to prevent morbidity and mortality from upper GI manifestations of LS (early-stage cancer observed in about 1.5% of asymptomatic patients3Farha N. Hrabe J. Sleiman J. Beard J. et al.Clinically actionable findings on surveillance EGD in asymptomatic patients with Lynch syndrome.Gastrointest Endosc. 2022; 95: 105-114Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar).

Histoarchitecture of Large Intestine and Lympho Glandular Complex of Pig

Background: To have a better understanding of the lympho glandular complexes (LGC) along with the histoarchitecture of large intestine and associated M cells, the proposed study have been undertaken. Methods: Present study was conducted on 12 (twelve) numbers of apparently healthy weaned crossbred piglets of 3 to 4 months irrespective of sex. After humane sacrifice of the animals with the approval of institutional animal ethics committee, the representative tissue samples were collected preserved, processed and stained as per standard methods of Luna (1968). Result: Columnar cells predominated the follicle associated epithelium (FAE) and the crypts. M cells were recorded in the follicle associated epithelium as well as in lower crypt epithelium in toluidine blue stained ultra thin sections. M cells were observed with intraepithelial lymphocyte and basally placed euchromatic nucleus. In the colon and rectum of crossbred pigs the lympho glandular complex (LGC) typically consisted of a pore like depression on surface epithelium from which extensions of mucosal glands passed through the circular gap into lamina muscularis mucosae. The lymphatic aggregation of LGC in the lamina propria and tunica submucosa showed three distinct zone viz. follicle, interfollicular area and dome area and distinct FAE could be appreciated. The epithelium lining the solitary lymphatic nodule (SLN) showed (Periodic acid-Schiff) PAS positive reaction. The mucous substance showed strong reaction in the gland in LGC and the FAE epithelium the number of goblet was less. The LGC was formed by aggregation of lymphoid follicles with invagination of crypt gland inside the follicle in the tunica sub mucosa. The follicle associated epithelium devoid of goblet cells were observed on the LGC with interspersed of diffuse migrating lymphocytes in the lamina propria. In the LGC, secondary follicle with interfollicular area was appreciated. In mesenteric lymph node the secondary follicles with inner germinal centre and outer corona could be seen in cortico medullary area. Meshwork of reticular fibers was abundantly present around the crypts in the lamina propria and in the pore like depression of LGC and around the secondary follicle. Collagen fibers could be seen surrounding the LGC and glands. Scanty collagen fibres were observed in the inter-follicular glands. Innervations of nerve fibre was observed around the lymphoid follicle and penetrating the LGC. The mucosal glands were PAS positive.

HISTOLOGIC AND MICROMETRIC STUDY OF THE PROVENTRICULUS AND GIZZARD OF THE WILD BRONZE TURKEY (MELEAGRIS GALLOPAVO)

The purpose of the present study was to investigate the histologic and micrometric study of the proventriculus and gizzard of the wild bronze turkey (Meleagris gallopavo). Thirty clinically healthy Bronze turkeys (15 females and 15 males) were used for the study. Twelve tissue samples (six from the proventriculus and six from gizzard) from the corresponding age group were used to prepare histological slides. The preparations were stained with hematoxylin (Erlich) - eosin and Masson’s trichrome. The wall of the proventriculus was composed of four layers. They were tunica mucosa, tunica submucosa, tunica muscularis and tunica serosa. Mucosa had many grooves and plicae with simple columnar epithelium. The proventricular submucosa had compound tubuloalveolar glands which took the greatest part of the wall. The gizzard had tunica mucosa, tunica muscularis and tunica serosa. Compound tubular glands were found in the mucosa. On the mucosal surface was observed a thick keratinized layer, which was produced by the glands. In lamina propria mucosae were found compound tubular glands which opened on the mucosal surface by a short neck. The glands in the grooves were more branched, compared to those localized in the folds. Lamina muscularis mucosae was not found.

Histological and histometric study of the small intestine in Stara Zagora white turkey in age aspect

Thirty clinically healthy Stara Zagora white turkeys (15 females and 15 males) were used for the study. Eighteen tissue samples (six from the middle of each segment of the small intestine) of the appropriate age group were used to prepare permanent histological specimens. The histological sections were stained by Masson - Goldner method. The small intestine of the Stara Zagora white turkey was composed of four tissue layers: tunica mucosa, tunica submucosa, tunica muscularis and tunica serosa. Tunica mucosa had lamina epithelialis, lamina propria and lamina muscularis mucosae. The layers of the mucosa formed well-defined intestinal villi - villi intestinales. Lamina epithelialis was composed of highly differentiated simple columnar epithelium. Tunica mucosa in the three segments of the small intestine had clearly distinct tubular glands - gll. Intestinales. The histometric results showed that the growth of the mucosal structures and the mucosa was more intense in the first twenty-eight days, compared to the growth of the other layers of the intestinal wall. The most intense was the increase in the height and area of the intestinal villi. The height of the intestinal villi varied most markedly during the first twenty-eight days of the duodenal examination, while the area of the villi increased most in the jejunum, followed by the ileum and duodenum. The height of the intestinal epithelium increased most intensively 2.3 times in the jejunum mucosa. The thickness of the jejunal mucosa increased the most during this period, compared to the mucosa of the duodenum ileum.

S3131 An Unusual Case of Postprandial Diarrhea: Gastrocolic Fistula from Gastric Band Erosion

Introduction: Bariatric surgery is increasingly performed nowadays. Gastroenterologists may encounter patients with its complications. Known complication of laparoscopic adjustable gastric banding (LAGB) include reflux, band slippage, erosion, pouch enlargement, and port breakage. We report a case with an unusual complication of LAGB. Case Description/Methods: A 45-year-old male with LAGB and atrial fibrillation presented with chronic diarrhea. Symptoms onset was 3 years ago after his partial small bowel resection when he presented with peritonitis. The patient reported loose stool within 15 minutes after each meal, abdominal pain, and 13-lbs weight loss. Physical exam was unremarkable. Laboratory data were within normal limits except mild anemia (Hgb of 12.9 g/dL) and mild renal impairment (Cr of 1.55 mg/dL). Upper GI study with small bowel follow through showed two separate channels arising from the proximal stomach with one connecting to the mid-transverse colon, suggesting a gastrocolic fistula (GCF) (figure 1A). CT scan of chest/abdomen/pelvis that was performed prior to barium studies was reviewed and demonstrated gastric erosion of the LAGB, with tethering of gastric cardia to the transverse colon with prolapse of the tubing into the distal transverse colon (figure 1B). Subsequent upper endoscopy showed an eroded gastric band in the gastric cardia and appeared to be extending through the gastric wall (figure 1C). Colonoscopy noted gastric band was entering transverse colon and extended distally (figure 1D). Surgical specimen of previous small bowel resection was reviewed and didn't show small bowel ischemia nor small bowel Crohn’s disease. The patient is currently evaluated by a bariatric surgeon for the definite treatment. Discussion: GCF is an uncommon manifestation of certain malignancies, pancreatitis, Crohn’s disease, peptic ulcer disease, and few cases related to other bariatric surgeries, usually with sleeve gastrectomy. LAGB related erosions of stomach, colon, and small bowel have been reported. To best of our knowledge, there are only 3 other cases of GCF related to LAGB. We report a rare complication of LAGB. Mechanism of GCF from LAGB is not fully understood, and is likely related to erosion of gastric wall from band pressure or foreign body reaction. Symptoms includes abdominal pain, weight loss, diarrhea, and sepsis. Diagnosis is made with upper GI series, contrast enhanced CT and endoscopic visualization. Surgery is the mainstay of treatment with removal of band and closure of fistula.Figure 1.: Endoscopic image of gastric ulcer in first case (A). Microscopic image H&E stained 400x of lymphoepithelial lesion with surrounding lymphocyte mucosal invasion (B). Endoscopic image of polypoid lesion in second case (C). Microscopic image H&E stained 200x of diffuse lymphocyte invasion into the lamina propria and muscularis mucosa (D).

S3169 An Unusual Cause for Persistent Anemia: Gastric Amyloidosis

Introduction: This case highlights an unusual presentation of amyloidosis and multiple myeloma which was discovered during endoscopic and histological evaluation of the gastrointestinal tract for persistent anemia. Thus, it is important to consider these underlying malignancies during work up of anemia with proper biopsies and staining. Case Description/Methods: 67 year old woman with Zenker’s diverticulum and chronic gastrointestinal symptoms attributed to IBS presented for persistent iron deficiency anemia of Hgb 10 and rectal bleeding. A 2 cm sigmoid colon Hamartomatous polyp and a 4 mm cecal tubular adenoma were resected during colonoscopy with normal terminal ileum. While rectal bleeding resolved, surveillance colonoscopy in 6 months showed no residual polyp. Due to persistent anemia despite iron replacement, she underwent an EGD which showed a grossly normal stomach and mild duodenitis. Random biopsies of antrum and duodenum showed acellular pink/amorphic matrix in lamina propria and muscularis mucosa with green birefringence on congo red staining, consistent with amyloid. The patient was referred to hematology/oncology for further work up of amyloidosis. SPEP and immunofixation showed IgA monoclonal gammopathy and free light chain assay revealed 2401.9 mg/L kappa light chains, with a kappa/lamda ratio of 343.13. UPEP showed M spike with positive Bence Jones protein, kappa type. Bone marrow biopsy revealed 13% plasma cells. Patient was diagnosed with amyloid light chain amyloidosis and multiple myeloma and began treatment with systemic chemotherapy. Later in the course, patient had recurrence of rectal bleeding. Repeat colonoscopy was normal, but EGD showed multiple small gastric ulcers which was felt to be the sequelae of gastric amyloidosis. Discussion: Gastric amyloidosis as the presenting pathology of multiple myeloma is rare. Symptoms include abdominal pain, bleeding, motility issues, and malabsorption. Endoscopic findings most commonly show ulcerations, mucosal erosions, and submucosal hematomas. Because these findings are nonspecific, it can be difficult to diagnose unless the clinician has high suspicion for the disease. In our patient’s case, the initial investigation was prompted due to persistent anemia. Unlike the typical mucosal abnormalities seen in gastric amyloidosis, our patient had grossly normal mucosa. Only after biopsies of the stomach and duodenum to rule out H. pylori and celiac disease were performed did we discover the patient had amyloidosis and ultimately multiple myeloma.

Acquired Esophageal Strictures in Children: Morphometric and Immunohistochemical Analyses.

Esophageal strictures (ES) in children are not well characterized pathologically. We report unique histopathologic analyses of resected acquired ES and control esophagi (CE). Muscle layer thicknesses were measured in intact well-oriented areas; inflammatory cells were counted in the most inflamed high power field (hpf). Sections were stained with relevant antibodies. Results were expressed as median, lower and upper quartiles. Wilcoxon Rank Sums non-parametric test was used to compare groups; P ≤ 0.05 was considered significant. All ES (N = 10) showed focal replacement of lamina propria, muscularis mucosa and submucosa by actin+ fibers emanating from muscularis propria. Compared to CE (N = 8), ES displayed significantly thickened muscularis mucosa and propria, and increased mast cells (tryptase- and chymase-positive), and eosinophils in muscle layers (all P ≤ 0.01). Matrix proteins periostin and fibronectin were identified in the muscle layers of CE, and in the extracellular matrix in areas of disrupted architecture in ES. Compared to CE, acquired ES in children show significant structural alterations, including obliterative muscularization, inflammatory cell mural infiltrates, and extracellular matrix protein deposits. Therapies targeting connective tissue expansion, mast cells, eosinophils and inflammation may be beneficial to treat ES.

Primary Intestinal Lymphangiectasia in a Middle-Aged Female.

Primary intestinal lymphangiectasia (PIL) is a rare disorder caused by impaired intestinal lymphatic drainage due to congenital lymphatic hypoplasia. It was first described by Waldman et al. in 1961,[1] about 205 cases have been reported.[2] The disease usually manifests before 3 years of age, and only occasionally diagnosed in adulthood. Here, we report a case of a middle-aged female who presented with chronic diarrhea and was finally diagnosed as a case of PIL. A 49-year-old female presented to the Outpatient Department of our hospital with complaints of diarrhea for 2 years. The patient reported an occurrence of diarrhea four to five times daily, which was semisolid to watery in consistency with absence of blood, mucus, or oil. The diarrhea was also not associated with tenesmus, urgency, or pain in the abdomen. On examination, her body mass index was 18 kg/m2 and there was presence of bilateral pitting edema in the lower limbs. Routine laboratory investigation revealed hemoglobin of 9 gm/dl, total leukocyte count of 4100/mm3 with 14% of lymphocytes, platelet count of 1.6 lakh/mm3 and hypoproteinemia (serum protein, 3.90 gm/dl; serum albumin, 2.10 gm/dl; serum globulin, 1.8 gm/dl). She was non-reactive for HIV and hepatitis B. Stool routine and microscopic examination was negative on three occasions and culture was negative. Upper gastrointestinal endoscopy revealed multiple scattered whitish spots in the second part of the duodenum [Figure 1]. Multiple biopsies from it revealed dilated lymphatic channels in lamina propria, muscularis mucosae and submucosa [Figure 2]. Therefore, a diagnosis of intestinal lymphangiectasia (IL) was made and further work up was done to rule out secondary causes. Her colonoscopy with terminal ileoscopy, contrast-enhanced computed tomography of chest and abdomen, echocardiography, autoimmune profile, immunoglobulin levels and hormonal profile were all normal except for reduced immunoglobulin levels. Accordingly, a final diagnosis of PIL was made and the patient was started on a low-fat, high-protein diet with medium-chain triglyceride (MCT) supplementation. Subsequently, her condition improved, and the diarrhea stopped after 1 month. The upper gastrointestinal endoscopy was repeated after 6 months, and the findings were normal with no whitish spots in the duodenum [Figure 3].Figure 1: Upper gastrointestinal endoscopy showing whitish spots in the second part of duodenumFigure 2: Duodenal biopsy showing dilated lacteals in mucosa and submucosaFigure 3: Normal upper gastrointestinal endoscopy after 6 months of dietary modificationPIL is a congenital malformation that presents with chronic diarrhea and malabsorption and is diagnosed after ruling out secondary causes. Its late onset can be explained by the patchy involvement of the small bowel. Secondary intestinal lymphangiectasia can occur due to various causes such as constrictive pericarditis, intestinal lymphoma, intestinal tuberculosis, sarcoidosis, scleroderma, Whipple's disease, Crohn's disease, autoimmune polyglandular syndrome and radiation or chemotherapy induced retroperitoneal fibrosis.[3] Intestinal lymphangiectasia in adults has few or no features of malabsorption, as in our case. Its diagnosis is done by specific endoscopic features and corresponding histopathological findings. Endoscopic features of intestinal lymphangiectasia are scattered white punctate snowflake lesions in small intestine due to dilated lacteals that cannot be washed away. Upper gastrointestinal endoscopy can diagnose 86% of intestinal lymphangiectasia cases.[4] Histopathology of small bowel will show characteristic dilated lacteals in the mucosa and submucosa. The cornerstone of its treatment is diet modification. Diet should be low in fat with substitution of long chain fatty acid with MCT, as it directly enters the portal venous system bypassing the intestinal lacteal system, thereby preventing lacteal engorgement and rupture.[5] Most of the patient respond with this treatment in few weeks with reversal of clinical and biochemical signs. In conclusion, PIL is a rare cause of chronic diarrhea, especially in adulthood, that requires meticulous examination of duodenum, as early diagnosis and treatment can reduce the morbidity and mortality. Declaration of patient consent The authors certify that they have obtained all appropriate consent forms from the patient. The patient has given her consent for images and other clinical information to be reported in the Journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal the identity. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Differentiation of early gastric cancer infiltration depths using nonlinear optical microscopy

Gastric cancer, one of the most common malignant tumors that can affect the digestive system, poses a serious threat to human life. The survival rate of gastric cancer patients depends on early detection and treatment. The widespread adoption of endoscopy has improved the detection rate of early gastric cancer. Accurate preoperative diagnosis of early gastric cancer is key to developing individualized treatment strategies. Here, nonlinear optical microscopy (NLOM) is used to differentiate between normal gastric mucosae and those with early gastric cancer. Furthermore, the quantitative relationship between submucosal infiltration depth and collagen signals in early gastric cancer is explored. First, the two-dimensional collagen direction angle was measured as an indicator to identify cancerous tissue. The orientation indexes of collagen fibers in normal and cancerous tissues were found to be 0.8511 ± 0.0839 and 0.6466 ± 0.07429 (P < 0.0001), respectively, indicating a significant decrease for the cancerous site. The backscattered second harmonic generation (SHG) signal corresponding to the collagen content and the three-dimensional collagen fiber orientation were then studied for early gastric cancer at different infiltration depths. The backscattered collagen SHG signal (a.u.) in the infiltrated lamina propria, muscularis mucosa, and submucosa were found to be 0.1850 ± 0.0393, 0.0870 ± 0.0189, and 0.0435 ± 0.0163, respectively. The 3D directional variance of collagen corresponding to the three infiltration depth sites were 0.6108 ± 0.0707, 0.6794 ± 0.0610, and 0.8200 ± 0.0618 (P < 0.05), respectively. Significant differences between the early gastric cancer collagen signals at different infiltration depths were observed. Our results indicate that NLOM can differentiate cancerous tissue from normal tissue, and thus diagnose early gastric cancer based on infiltration depth. NLOM provides a new evaluation method for the real-time in situ diagnosis of early gastric cancer and has important clinical significance for preparing accurate individualized treatment guidance.