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Background The efficacy of endoscopic ultrasound (EUS) for determining the T category of gastric cancer is variable. The aim of this study was to evaluate the superiority of EUS by using the 6th edition American Joint Committee on Cancer (AJCC) staging system for stomach cancer compared to the new 7th/8th edition. Methods A retrospective analysis of clinical and EUS imaging features of 348 gastric carcinoma patients who underwent radical resection were retrospectively analyzed. Differences between the 6th and 7th/8th edition T staging systems for preoperative EUS evaluation were compared. Results The accuracy of EUS T staging was 72.4% for the 7th/8th edition and 78.4% for the 6th edition. T3 stage accuracy was significantly worse when the T3 group status was changed. The tumor location, echoendoscope type, and histological type were associated with inaccuracy. We further analyzed the EUS image features for each tumor T stage and found that an indistinctly visible muscularis propria (MP) or with obvious thickening was considered an indicator of lesions involved in the MP with a sensitivity of 81.3%; an MP completely disappeared and accompanied with a serosal layer intact may be a marker that the lesion invaded to the subserosa. We also found that irregularities in the outer edge of the gastric wall were markers of gastric serosal layer penetration with a positive predictive value of 92.2%. Conclusions The increased complexity of the 7th/8th edition T staging system is accompanied by worsening of the predictive accuracy for EUS as compared to the 6th edition. Furthermore, the tumor location, echoendoscope type, histological type, and EUS image features for each tumor T stage should warrant attention.

AIMS To investigate the relationship between lower urinary tract function and the accessory nerve (ACN) arising from the major pelvic ganglion (MPG). METHODS Ten-week-old male Wistar/ST rats were randomly divided into eight groups according to the type of treatment (sham or bilateral accessory nerve injury [BACNI]) and the duration of observation (3 days, 1 week, 2 weeks, or 4 weeks: Sham-3d, Sham-1w, Sham-2w, Sham-4w, BACNI-3d, BACNI-1w, BACNI-2ws, and BACNI-4w. BACNI was induced in the following manner: the ACN was crushed for 1 min (2 mm away from the MPG) using reverse-action tweezers. The same procedure was performed on both sides. On the last day of each observation period, the bladder function was measured by awake cystometry, and histological evaluation was performed. RESULTS All rats in the Sham groups micturated normally. In the BACNI-3d and BACNI-1w groups, all rats showed symptoms of overflow urinary incontinence (OUI). This OUI improved gradually over time. The bladder's size in the BACNI group was significantly larger than that in the Sham group (p

Despite significant advances in understanding the role of the immune response in Opisthorchis viverrini-associated carcinogenesis, little is known about how infection induces gall bladder disease. This study investigated whether mast cells are activated in cholecystitis associated with O. viverrini, gall bladder specimens from ninety-two patients who had undergone cholecystectomy at the Khon Kaen Regional Hospital, Khon Kaen, Thailand. Two representative sections from the body of fresh gall bladder tissue were fixed in Carnoy’s solution and embedded in paraffin wax. The paraffin sections were stained for mast cells and IgE plasma cells by the double histochemical and immunohistochemical method. The cells in the epithelium, lamina propria, muscular layer, and subserosa were counted and expressed as cells per square millimeter. The gall bladder bile was examined for the presence of O. viverrini eggs. Significantly higher mean mast cell numbers were found in the lamina propria (221.41 ± 16.01 vs 116.97 ± 14.61 cells per mm2; P < 0.005) of egg positive compared to egg negative groups, respectively. No comparable differences in mast cell number were observed in other layers. IgE plasma cells were rarely seen. The results suggest that mast cell hyperplasia occurs during cholecystitis in association with opisthorchiasis and may play a role in the pathogenesis of the disease.

Gastric cancer represents the fifth most common malignancy and the third leading cause of cancer mortality with widely varying incidence worldwide. Adequate tumor staging is essential to define the most appropriate therapeutic strategy and to provide accurate pre-treatment risk stratification. Gastric cancer can be divided into early- and advanced-stage. Endoscopic ultrasound (EUS) is the best-studied modality for the staging of early gastric cancer. It allows visualization of the five layers of the gastric wall, and evaluation of the degree of tumor invasion and the presence of suspicious malignant lymph nodes. It is not clearly indicated when there is evidence that the cancer is invasive. Early-stage gastric cancers are limited to the mucosa or submucosa, regardless of the presence of lymph node metastasis, whereas tumors that infiltrate into or beyond the subserosa to nearby organs or metastasize are advanced gastric cancer. Diagnosis of malignant lymph nodes can be confirmed with the use of fine-needle aspiration biopsy for cytological evaluation.

Solitary fibrous tumors are rare tumors of mesenchymal origin. Although most often observed in the lung pleura, they have been reported in varied extrapleural sites. A 70-year-old male with complicated Crohn’s disease presented with 3 days of nausea, emesis, constipation, and abdominal pain. Computed Tomography (CT) demonstrated mucosal thickening of the middescending colon, consistent with fibrosing stricture. Surgical excision revealed an unusual, 5 cm mass originating in the subserosa. Histopathology of the lesion was notable for a proliferation of cells with spindle and stellate-shaped nuclei and no appreciable mitotic figures, which extended into the muscularis and submucosa. Immunohistochemistry was STAT6 nuclear positive and cytoplasmic CD34 positive, diagnostic for solitary fibrous tumor (SFT). In this case, the SFT infiltrating into the muscularis propria and subserosa caused the stricture and bowel obstruction. This illustrates that while fibrosing strictures are usually the etiology of bowel obstruction in the setting of Crohn’s disease, other rare possible causes should be considered. Published version

Background Using indocyanine green (ICG) fluorescence imaging and tissue marking dyes (TMDs), perigastric lymphatic mapping and their pathological correlation were examined to see whether ICG staining covers all metastatic lymph nodes (LNs) in advanced gastric cancer (AGC). Methods Patients with AGC who underwent open distal or total gastrectomy were enrolled. ICG was serially injected intraoperatively into the subserosa along the greater and lesser curvatures. Stomach specimens were examined under a near-infrared camera. ICG-stained LNs were named, excised, and tattooed with different colored TMDs to retrace the exact location after pathological examinations. Results A total of 687 LNs and 69 LN stations were examined from 11 patients. The map of the perigastric lymphatic network showing the topography of ICG-stained and ICG-unstained LNs, including metastatic information, was successfully reconstructed. The average number of ICG-stained and ICG-unstained LNs were 23.6 ± 12.3 (37.8%) and 38.8 ± 17.1 (62.2%), respectively. LN metastases were present in 28 LN stations of 8 patients. Of 8 cases with LN metastases, 40% (11.1–75% per case) of metastatic LNs were stained by ICG. Of 28 metastatic LN stations, 21 (75.0%) were covered by ICG, and actual metastatic LNs were stained in 16 LN stations (57.1%). In 4/8 cases (50%), all metastatic LN stations showed ICG signals. Conclusions ICG fluorescence imaging and TMD are useful tools for visualizing the perigastric lymphatic network and retracing the exact location of ICG-stained LNs in AGC. However, ICG imaging is still not recommended for selective LN dissection in AGC because of the limited staining of perigastric LNs.

Background: Despite significant progress in the research of fibrosis in various organs, fibrosis remains a poorly understood complication of Crohn's disease (CD). We analyzed pathologic features of fibrosis and inflammation in CD and compared them with the normal bowel, aiming to clarify whether fibrosis in CD pathogenetically resembles fibrosis in other organs. Methods: Resection specimens from 30 patients with CD were included. Normal bowel from resection specimens of colorectal carcinoma was used for comparison. Trichrome Masson staining, immunohistochemistry for α-smooth muscle actin, fibroblast activation protein, CD34 and erg, in situ hybridization for TGF-β1 and analysis of selected fibrosis-related microRNAs were performed. Results: In normal bowel, CD34-positive fibroblasts/pericytes were detected in the submucosa and subserosa, particularly around blood vessels. In CD, fibrosis prevailed in the submucosa and subserosa, together with proliferation of myofibroblasts and disappearance of CD34-positive fibroblasts/pericytes. TGF-β1 was present in the lamina propria in normal bowel and CD, and in deeper parts of the bowel wall in CD. MicroRNAs miR-29c, miR-155 miR-150, and miR-155, which have been demonstrated to contribute to fibrosis in various organs, showed significant deregulation in CD. Conclusions: Distribution of fibroblasts/pericytes in the submucosa and subserosa of normal bowel, their disappearance in fibrosis in CD, together with the appearance of myofibroblasts, suggest that fibroblasts/pericytes are the most likely source of myofibroblasts in CD. Furthemore, fibrosis-related microRNAs showed deregulation in fibrotic areas. Pathogenesis of fibrosis in CD is thus comparable to fibrosis in other organs, in which myofibroblasts are the key effector cells, and pericytes have emerged as the main origin of myofibroblasts. Fibrosis in CD should be regarded as a result of (over)response of the bowel wall to the presence of inflammation in deep structures of the bowel wall, presenting another example of a common pathogenetic pathway of fibrosis development.

Pneumatosis intestinalis is a rare condition characterized by the presence of gas in the submucosa or subserosa of the intestinal wall. We report two cases associated with generalized abdominal pain and rebound tenderness. The computed tomography (CT) scans in both cases showed bowel distention, pneumatosis intestinalis and portal venous gas. Both patients underwent emergency surgery which demonstrated bowel necrosis with mesenteric ischemia, consistent with the CT images. Both patients died (one during surgery and the other in the immediate postoperative period).

A 7-month-old female mixed breed foal with a 2-day history of recumbency and inability to open its mouth convulsed acutely and died and was submitted for necropsy examination. The foal was thin and large patches of haemorrhage were present throughout the peritoneal wall, the diaphragmatic surfaces and the retroperitoneum. Numerous nematode larvae were visible on the serosal surfaces and penetrated and embedded into the subserosa associated with the haemorrhages. The dorsal portion of the abdominal diaphragm had a partial tear and large numbers of nematodes were within the muscle fibres. Histologically, the larvae had a smooth cuticle, polymyarian/coelomyarian musculature and multinucleated intestinal cells, and were typically surrounded by haemorrhage, neutrophils, dense fibrovascular connective tissue and rare multinucleated giant cells. Parasitological examination identified the larvae as Strongylus edentatus based on the morphology of the buccal capsule. Additionally, there was severe muscle necrosis of the tongue and liver tissue analysis detected selenium deficiency. S. edentatus infections are uncommon in California, USA, and are typically non-lethal. In this case, the selenium deficiency may have led to immunosuppression, resulting in the hyperinfection with S. edentatus, and to the muscle damage and tear of the diaphragm. Although ivermectin treatment was indicated in the history, inadequate deworming or anthelmintic resistance may have played a role in the severity of infection.

A 70-year old man had multiple lung nodules detected on a computed tomography (CT) performed as part of the work-up for an isolated episode of hematuria of several hours' duration. A CT-guided lung biopsy disclosed a morphologically undifferentiated neoplasm, that could not be further subclassified despite an extensive immunohistochemical panel.Four years previously the patient had undergone a left hemicolectomy in another institution to resect a 4.7 cm polypoid ulcerated area in the splenic flexure. The slides from that resection were retrieved for review at our institution. There was a variably cellular, diffuse spindle cell neoplastic proliferation involving the submucosa, muscularis propria and subserosa of the large bowel, composed of elongated spindle cells, with small, inconspicuous nucleoli, arranged in intersecting fascicles. Occasional areas of the tumor showed myxoid stroma. Mitotic activity was low.Immunohistochemistry showed strong and diffuse cytoplasmic staining for MUC4 in both the large bowel and lung tumors. Molecular profiling identified a FUS-CREB3L1 fusion gene.The constellation of morphological, immunohistochemical and molecular features are of low-grade fibromyxoid sarcoma (LGFMS) of the large bowel, with metastatic fibromyxoid sarcoma to the lung.LGFMS is a malignant, often late-metastasizing tumor, with a misleadingly bland histological appearance, that typically arises in the deep soft tissues of the proximal extremities or trunk of young adults. Accurate classification, requiring morphology and ancillary tests, is required for appropriate clinical follow-up and treatment of patients. Keywords: Colon, Low-grade fibromyxoid sarcoma, Metastasis, Lung

Background If the depth of gallbladder malignant tumor (GBMT) invasion is deeper than the subserosa (ss), cholecystectomy is insufficient. In past reports that used endoscopic ultrasonography (EUS) to diagnose the depth of tumor invasion, it was difficult to diagnose GMBT invasion in the ss without a narrow or disrupted lateral hyperechoic layer (LHEL). Therefore, we developed a simple preoperative method to diagnose GBMTs with ss invasion. Methods Forty-nine GBMT patients who underwent both EUS and surgery were enrolled: 15 patients whose tumors invaded the mucosa (m) or muscularis propria (mp) were classified as the “shallow group”, and 34 patients whose tumors invaded the ss were classified as the “deep group”. The EUS findings were compared between the two groups. Results An irregular (narrow or thickened) LHEL was significantly more frequently observed on EUS in the deep group than in the shallow group. The diagnosis of ss invasion based on an irregular LHEL had the highest sensitivity and accuracy among the EUS imaging parameters (sensitivity 97.1% (33/34), specificity 86.7% (13/15), accuracy 93.8% (46/49)). When the deep group was limited to patients with a tumor depth of ss, the results were similar. When an irregular LHEL was used, the diagnostic accuracy of GBMTs with ss invasion was not significantly different between EUS specialists and beginners. Conclusions The observation of an irregular (thickened or narrow) LHEL observed on EUS could be a reliable and simple method of diagnosing GBMTs with ss invasion and could contribute to choosing an appropriate surgical method.

Background Adenomatoid tumors (AT) are benign neoplasms of mesothelial origin that occur more frequently in the genital tracts. In uterus, AT are usually located in the subserosa of the cornual myometrium. Microscopically, it is characterized by interanastomosing pseudoglands or pseudovascular spaces and striking smooth-muscle hypertrophy is often present. In some cases, the prominence of smooth muscle component simulates a leiomyoma and the lesion is denoted as a leiomyoadenomatoid tumor. The microscopic appearance of the adenomatoid component (AC) may mimic a malignant tumor due to irregular pseudoinfiltration with tubular formations. Just 16 cases with this morphological presentation were found in the literature review. Case presentations The first case, a 38-year-old female, showed lower abdominal pain, menorrhagia, postcoital bleeding and previous history of uterin leiomyoma. The second case, a 26-year-old female, had clinical complaint of metrorrhagia and received diagnostic hypothesis of leiomyoma after ultrasound image. Both underwent myomectomy. Microscopically, the uterine masses showed intersecting smooth muscle bundles and gland like areas lined by cuboidal epithelioid cells that stained positive for WT1, D2–40 and calretinin in immunohistochemical analysis. Conclusions The cases were diagnosed as leiomyoadenomatoid tumor of the uterus. This is a benign and rare entity that may mimic malignant tumors due to the pseudo infiltrative appereance of the adenomatoid component, possibly leading to misdiagnosis.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the human gastrointestinal tract. They usually develop in the stomach and small intestine, but extremely rarely in the colon. Although most GISTs form a mass, some cases showing a flatly proliferating lesion called planar-type GIST have been reported in the sigmoid colon and small intestine. Those are often associated with diverticular lesion and/or perforation. We present here a case of planar-type GIST of the transverse colon with perforation. A 49-year-old Japanese woman abruptly complained of abdominal pain, and was clinically diagnosed as perforation of the transverse colon. Partial resection of the transverse colon including the perforated site was done, and no apparent mass lesion was present. Histology showed that spindle cells flatly proliferated around the perforated area and replaced the layers from submucosa to subserosa. Immunohistochemistry revealed that the spindle cells were KIT-, DOG1- and CD34-positive. Codons 557 and 558 of exon 11 of the c-kit gene were heterozygously deleted at the lesional tissue but not at the normal mucosal tissue. Planar-type GIST of the transverse colon has not been reported yet, and the literature search for the similar cases was done.

Pneumatosis intestinalis (PI) is a rare condition characterized by multiple air-filled cystic lesions in the submucosa or subserosa of the intestine. Despite a limited understanding of its pathogenesis, the causes of PI can be categorized into life-threatening or benign, which helps guide patient management. For benign etiologies, interventions should be minimized and endoscopic maneuvers should be avoided as most of these cases can be managed conservatively. We present a patient with asymptomatic, benign PI who subsequently developed symptoms following cyst biopsy during a screening colonoscopy.

Pancreatic heterotopia is defined as pancreatic tissue outside its normal location in the body and anatomically separated from the pancreas. In this work we have analyzed the stomach glandular epithelium of Gata4 flox/flox; Pdx1‐Cre mice (Gata4KO mice). We found that Gata4KO glandular epithelium displays an atypical morphology similar to the cornified squamous epithelium and exhibits upregulation of forestomach markers. The developing gastric units fail to form properly, and the glandular epithelial cells do not express markers of gastric gland in the absence of GATA4. Of interest, the developing glands of the Gata4KO stomach express pancreatic cell markers. Furthermore, a mass of pancreatic tissue located in the subserosa of the Gata4KO stomach is observed at adult stages. Heterotopic pancreas found in Gata4‐deficient mice contains all three pancreatic cell lineages: ductal, acinar, and endocrine. Moreover, Gata4 expression is downregulated in ectopic pancreatic tissue of some human biopsy samples., ER‐S. was supported by a ‘Juan de la Cierva’ postdoctoral fellowship from the Spanish Ministry of Economy and Competitiveness (IJCI‐2014‐19251). LV was supported by a contract from Spanish Ministry of Economy and Competitiveness (RYC‐2013‐14533). This work was supported by grants from the Spanish Ministry of Economy and Competitiveness BFU2017‐82497‐P to AR, ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación co‐funded with Fondos FEDER, PI16/00175 to DAC, the Andalusian Ministry of Science and Innovation CTS‐7478 to DAC, and grant SAF2015‐70553‐R to FXR. CNIO is supported by the “Ministerio de Ciencia, Innovación y Universidades” as a Centro de Excelencia Severo Ochoa (SEV‐2015‐0510).

A woman in her 70 s was diagnosed with a tumor in her duodenal wall during a routine visit for diabetes. She subsequently underwent subtotal stomach-preserving pancreatoduodenectomy. Histologically, the tumor was present mainly in the duodenal wall, and atypical cystic ducts were seen in the muscularis propria and subserosa. Invasive well-differentiated adenocarcinoma was seen in the duodenal submucosal and mucosal layers. Heterotopic pancreatic tissue was seen within the tumor, and atypical epithelium had proliferated and replaced the cystic ductal epithelium of the heterotopic pancreas. Therefore, adenocarcinoma with intraductal papillary mucinous neoplasm arising in duodenal heterotopic pancreas was the final histopathological diagnosis, which is considered rare.

We aimed to assess and compare ex vivo MRI of resected colorectal carcinoma before and after formalin fixation. We enrolled 45 consecutive patients (47 carcinomas) who underwent colorectal carcinoma surgery. Specimens underwent two MR scans at 1.5 T (after resection and 24 h after formalin fixation). Two radiologists evaluated all MR images independently regarding T-staging and the subserosal linear architecture. T-stage accuracy and frequency of linear architecture were calculated. A third radiologist measured vertical tumor distance and contrast-to-noise ratio (CNR) of the mucosa, submucosa, muscularis propria, subserosa, and tumor. T-stage accuracy compared to histopathology by the two readers was 91.5% and 87.2% before fixation and 91.5% and 85.1% after fixation, respectively. Linear architecture was observed in 11.1% of T2 tumors and 100% of T3 tumors by both readers. The vertical tumor distance between histopathological and MRI findings was well correlated before and after fixation. The measurement error of the vertical tumor distance between before and after fixation was within 3 mm. CNR of the tumor was significantly lower than those of the submucosa and subserosa before and after fixation (p

We report 2 unusual elastotic lesions of intestinal subserosal fat. The first arose in the small bowel subserosa of a 64-year-old woman with volvulus. It was undetected macroscopically and consisted of a relatively circumscribed focus of elastosis, with essentially no evidence of fibrosis or blood vessel walls within. The second arose in the subserosa of the sigmoid colon in a 46-year-old woman with recurrent diverticulitis. It was also undetected macroscopically and consisted of a well-circumscribed nodule of elastic fibers surrounding prominent veins and arteries. Both patients had unremarkable postoperative courses. These lesions likely represent localized response to injury and are probably underrecognized.

Prominent cyst formation is an unusual feature of liposarcoma. We report here a case of dedifferentiated liposarcoma with huge cystic change without preoperative chemo- or radiation therapy. The lesion arose in the retroperitoneum juxtaposed to the right kidney of a 67-year-old woman. She underwent a surgical removal of the retroperitoneal cyst. The cystic tumor contained 1600 mL of old bloody fluid, and its wall was composed of edematous, inflamed or sclerosing fibrous tissue with fatty tissue containing abundant atypical stromal cells, which were immunohistochemically positive for MDM2 and CDK4, and demonstrated MDM2 gene amplification by fluorescence in situ hybridization. The wall was contiguous to an atypical lipomatous nodule located in the mesentery. The following surgical specimens of the right hemicolectomy and right nephrectomy revealed atypical cells infiltrating into the subserosa of the colon and the perirenal fat tissue or that in the renal sinus. This case indicates that well differentiated or dedifferentiated liposarcoma should be also considered as a differential diagnosis of perirenal cystic mass.

Introduction The aim of this study was to analyze the particularities of early gastric cancer (EGC) and their importance for staging, prognosis, and therapy. Material and methods A total of 338 GCs diagnosed and surgically removed in three medical institutes from Eastern Europe were retrospectively examined, and the EGCs were further examined. Besides the demographic factors and tumor characteristics, immunostains were performed with E-cadherin, HER-2, p53, Ki67, MLH-1, MSH-2, COX-2, VEGF-A, CD31, and CD105. Results From the 338 GCs, 29 were EGCs, the average being similar in Poland and Hungary (12.37% and 13.33% respectively) but lower in Romania (5.61%). The rate of lymph node metastases was 20.69% (n = 6). Two of the cases presented liver metastases, both of them having a multifocal aspect. In 1 of these cases, limited to the mucosa, intramural carcinomatosis of the lymph vessels was seen in submucosa, muscularis propria, and subserosa. COX-2 positivity was observed in 14 (48.72%) cases. COX-2 was directly correlated with microvessel density determined with CD31 (p < 0.001) and CD105 (p = 0.03). Same correlation with CD31 and CD105 was seen for HER-2 (p = 0.03 and p = 0.0007). The only negative independent prognostic factors for overall survival were tumor localization at the proximal stomach and male gender, regardless of age. Conclusions In EGCs, intramural carcinomatosis of the lymph vessels and multifocality should be separately described in every surgical pathology report, as indicators of aggressiveness. Microsatellite status, E-cadherin, HER-2, p53, and Ki67 do not have prognostic value in EGC, but the highly angiogenic pattern is a possible therapeutic target.

Pulse (hyaline ring) granuloma, a rare entity first described in lung and oral cavity, has been reported under various names before the identification of hyaline rings as fragments of pulses (the edible seeds of legumes). Similar lesions were thereafter described in extra-oral localizations, mainly the gastrointestinal tract, or localizations having potential communication with the gastrointestinal tract. Recently, 2 reports described “spiral bodies” surrounded by foreign body–type multinucleated giant cell reaction in pulse granulomas, corresponding to remnant plant vascular structures (helical xylem elements). In this article, we report a case of a 70-year-old male patient presenting to our hospital for an incisional hernia repair. He had a history of antrectomy 2 years previously for perforated duodenal ulcer complicated with fecal peritonitis. During the hernia repair procedure, multiple peritoneal whitish nodules and one subserosal appendiceal nodule were found. Appendectomy and biopsy of a peritoneal nodule were performed. Microscopic examination showed nodular lesions located in the subserosa to be pulse granulomas. Also surrounded by histiocytes, spiraled thin and rigid foreign bodies were identified. In this article, we report a case of pulse granuloma with spiral bodies complicating perforated duodenal ulcer and mimicking a peritoneal carcinomatosis. We also provide a discussion on the origin of spiral bodies in light of relevant literature.

The major role of conventional ultrasonography (US) can be divided into three processes: cancer screening, differential diagnosis, and assessment of the depth of tumor invasion. As US is a simple and minimally invasive modality, it is widely used for cancer screening and health checkups. Both gallbladder (GB) polyps and thickened wall of the GB are common US findings. On the contrary, US is prone to interference from gas echoes, and its diagnostic accuracy depends on both the US technology and the ability of sonographers. It is also important to be well acquainted with characteristic artifacts and how to manage their influence. Furthermore, magnified images acquired using high-resolution US (HRUS) are strongly helpful to pick up small lesions. As for differential diagnosis, classification of GB polypoid lesions (GPLs) into pedunculated or sessile (broad-based) types is very important. Cholesterol polyps in pedunculated lesions and localized adenomyomatosis (ADM) in sessile lesions are the most important targets to be differentiated. Furthermore, significant findings including number, size, growth rate, shape, internal echo, surface contour, and internal structure should be evaluated and judged as a whole. Usually, US delineates the GB wall as a two- or three-layer structure. However, as the inner hypoechoic layer includes not only the mucosa and muscularis propria but also the fibrous layer of subserosa, the differentiation between T1 (confined to the mucosa or muscularis propria) and T2 (invading the subserosa) based on the layer structure is difficult. Shape, size, and internal echo structure may be helpful for further assessment.

Background Ultrasound findings of shallow T2 gallbladder carcinoma (GBC) with a favorable prognosis are not known. Purpose To confirm the criteria for ultrasound diagnosis of shallow T2 GBC. Material and Methods A detailed analysis of ultrasound and pathological correlation was conducted in two patients with pT1 GBC and seven with shallow pT2 GBC (subserosal-invasion depth ≤ 2 mm) at our institution from January 1988 to December 2017. Results A polypoid gallbladder tumor with a deep hypoechoic area represented a papillary adenocarcinoma invading the subserosa accompanied by abundant fibrosis and lymphocytic infiltration. Two cases of pT1 GBC did not present a deep hypoechoic area, whereas all seven cases of shallow pT2 GBC did. One case of pT1b GBC and four cases of pT2 GBC showed conical thickening of the outermost hyperechoic layer, whereas one case of pT1a GBC and three cases of pT2 GBC presented no change of the layer thickness. All shallow T2 GBCs showing a conically thickened outermost hyperechoic layer provided good postoperative prognoses. Conclusion Ultrasound images of shallow T2 GBC show a deep hypoechoic area with conical thickening or unchanging of an outermost hyperechoic layer. The former demonstrates pulling up the top of the layer at first and then thinning later as carcinoma invades with enlargement of the hypoechoic area, whereas the latter thinning of the layer from the beginning. Polypoid gallbladder tumors with a deep hypoechoic area and a conically thickened outermost hyperechoic layer suggest shallow T2 GBC and may provide good postoperative prognoses.

EgeUn###, Primary intestinal lymphangiectasia is a rare disorder which characterized by unpaired small intestinal lymph drainage. There is loss of proteins from dilated lymphatic channels located in the mucosa, submucosa or subserosa which is results with loss of gammaglobulins and lymphocytes, leading to impaired humoral and cellular immunity. Herein, we present a 61-year-old patient with immunodeficiency secondary to Primary intestinal lymphangiectasia (PIL), in whom we could attain effective and stable IgG levels only by subcutaneous IgG replacement rather than intravenous IgG. Our experience suggests that Subcutaneous Immunoglobulin (SCIG) replacement resulted in more stable levels of IgG in the presented patient with PIL. We concluded that SCIG should be the preferred route of immunoglobulin replacement therapy in secondary hypogammaglobulinemia due to protein losing enteropathy, especially in PIL.

We experienced a rare case of gallbladder metastasis from renal cell carcinoma. A 68-year-old man was admitted for further evaluation of a gallbladder tumor, which had been identified on follow-up computed tomography after partial nephrectomy for renal cell carcinoma. Enhanced computed tomography and magnetic resonance imaging showed an enhancing polypoid mass in the gallbladder lumen. Endoscopic ultrasonography demonstrated a homogenous hypo-echoic polypoid lesion, and the outer hyper-echoic layer of the adjacent wall was intact. Blood flow signals in the wall side of the mass were observed on color Doppler endoscopic ultrasonography images. Laparoscopic cholecystectomy was performed and he was uneventfully discharged. Macroscopic examination of the specimen revealed a 12 × 7 × 5 mm pedunculated tumor attached by a thin pedicle to the fundus of the gallbladder. Histology confirmed a metastasis of the renal cell carcinoma that had infiltrated the shallow subserosa but had mainly grown into cavity of the gallbladder. These imaging findings are considered characteristic and may assist preoperative diagnosis in patients with a history of renal cell carcinoma.

Both the invasive growth types of colorectal cancer (CRC) and the number of myofibroblasts have been associated with histopathological factors such as lymph node and liver metastasis, and local recurrence. However, there are few studies, that have assessed the association between invasive growth type and myofibroblast distribution in CRC. We aimed to evaluate the relationship between the clinicopathological factors of CRC and two invasive growth types, the expanding and infiltrating types. We categorized 150 cases of pT3 CRC into the expanding and infiltrating types and measured the myofibroblast density of three histological layers: the submucosa (SM), the muscularis propria (MP) and the subserosa (SS). We compared these two invasive growth types and analyzed the relationship between clinicopathological factors and myofibroblast density. Myofibroblast density was significantly higher in the infiltrating type than that in the expanding type (P

Signet ring cell change of intestinal epithelial cells is a rare but well-known mimicker of signet ring cell carcinoma and is often associated with ischemic and/or pseudomembranous colitis. Instead, signet ring cell change involving nonepithelial cells in the subserosa of the intestine is an extremely rare finding with only a single case report in the literature to date. We report a new case of benign signet ring cell change localized in the subserosa of the large bowel incidentally identified in a resection specimen for Clostridium difficile colitis mimicking a metastatic signet ring cell carcinoma. Based on the morphologic features and immunohistochemical profile, we propose that these signet ring cells may possibly represent modified/degenerated fat cells. Furthermore, we discuss how to differentiate benign signet ring cells from a signet ring cell carcinoma.

Myofibroblasts of colorectal cancer (CRC) have been associated with histopathological factors such as lymph node metastasis, liver metastasis and local recurrence. However, few studies have assessed the association between these malignant potentials and the myofibroblast distribution in CRC. We aimed to evaluate the relationship between clinical factors and myofibroblast distribution around CRC invasive lesions. The study included 121 cases of pT3 CRC that were diagnosed at stage II or III. Myofibroblast density of the following three histological layers was measured: the submucosa (SM), muscularis propria (MP) and subserosa (SS). We analyzed the relationship between the clinicopathological factors and myofibroblast density by studying the histopathological features of the three layers. The myofibroblast density of the MP layer was significantly higher in the groups with high-frequency lymphatic and venous invasion than the groups with low-frequency lymphatic (P

A man in his early thirties presented to our clinic with right lower abdominal pain. Computed tomography (CT) and ultrasonography (US) revealed a swollen appendix and an appendicolith. Abscess formation was not observed but ongoing appendiceal rupture was not ruled out. Three months after successful conservative therapy, the lumen of the apical portion was kept dilated and laparoscopic interval appendectomy was performed. No tumorous findings were observed macroscopically. However, histology revealed many tiny nests infiltrating the submucosa, muscular layer, and subserosa at the root of the appendix. An appendiceal neuroendocrine tumor G1 (NET G1; carcinoid) was diagnosed immunohistologically. Neither CT nor US visualized the tumor because of its non-tumor-forming but infiltrative growth. In conclusion, after successful conservative treatment, interval appendectomy should be considered to uncover a possible appendiceal NET G1 (carcinoid), particularly when dilatation of the distal lumen is kept under observation.

Morphologically, an inflammatory fibroid polyp (IFP) is usually centred in the submucosa. Extension of an IFP to the subserosa with destruction of the muscularis propria is exceedingly rare. Herein, we describe a 70-year-old woman who presented with right lower abdominal pain but was finally diagnosed with an IFP. Contrast-enhanced computed tomography revealed a target-like structure with a hypovascular mass at the leading edge, which was consistent with intussusception due to a tumour. Following surgery, the resected specimen displayed a mass measuring 4 × 3 × 3 cm that was protruding into the lumen. Microscopically, the mass was centred in the submucosa, extending up to the mucosal surface and down to the subserosa and serosa. The muscularis mucosae and muscularis propria were destroyed focally. A PDGFRA gene mutation in exon 2 (1837_1851 del) that was found in this case, as well as a highly infiltrative growth pattern, strongly supported the neoplastic nature of IFP.

Squamous metaplasia of the appendix serosa is rare. We aimed to report the clinical and morphological features of 3 such cases. The patients presented with abdominal pain (n = 1 man, 2 women; age range, 29–35 years). The clinical diagnosis was appendicitis/periappendicitis (in the context of hydro/pyosalpinx). The surgical resected appendix showed several cystic and solid epithelial nests (1 mm and less) in the serosa/subserosa. Epithelial cells expressed p63, cytokeratin 5/6, as well as cytokeratins 7, 20, and CD10. Cystic and solid squamous and transitional epithelial nests of the appendix subserosa/serosa in adult patients may be revealed by acute appendicitis/ periappendicitis. The presence of such lesions, metaplastic or vestigial in nature, should be acknowledged since they can be misdiagnosed with metastatic epithelial tumor nests or they may undergo malignant change.

Locally advanced colorectal carcinomas are characterized by neoplastic cells that invade beyond the colon and directly into surrounding organs and structures that include the retroperitoneum and abdominopelvic sidewall. These aggressive tumors are prognostically adverse and are categorized with highest possible tumor stage in current cancer staging systems. Recognizing colorectal carcinoma with extensive locoregional invasion is typically straightforward, but some cases can be diagnostically challenging. These include tumors with limited invasion of extracolonic tissue such as the subserosa in which there are no cells or structures that are histologically or architecturally distinct from the colonic primary. Tumor-associated injury of the colonic peritoneum often precedes invasion by the neoplastic cells and can cause the peritoneal membrane of the colon to adhere and subsequently fuse to the peritoneal membrane of a neighboring organ or structure, thereby creating a trans-peritoneal bridge through which a tumor can directly invade the adherent extracolonic tissue. Hence, locally advanced colorectal carcinoma can be narrowly defined by neoplastic cells that completely invade through the fused peritoneal membrane and into the subserosa of the adherent extracolonic tissue. The evaluation of tumor invasion of the fused peritoneal membrane, which is enhanced by the combined use of an elastic stain and an immunostain for pan-keratin, is essential for the proper staging of locally advanced colorectal carcinoma and its clinical management.

Electric stimulation (ES) could induce contraction of intestinal smooth muscle. The aim of this study was to analyze the effects of ES on esophageal motility and the underlying mechanism in vivo. Twenty-eight rabbits were equipped with a pair of subserosa electrodes (connected to an electrical stimulator) in the lower segment of the esophagus. The ES signal consisted of bipolar rectangular pulse trains, lasting for 3 s, with different amplitudes (1 mA, 3 mA, 5 mA and 10 mA), and frequencies (10 Hz, 20 Hz and 50 Hz). The amplitude of the contraction was recognized by high-resolution manometry. The effect of ES was tested under anesthesia and following administration of atropine, phentolamine or L-NAME. ES induced esophageal contraction at the stimulated site. A statistically significant increase in esophageal pressure was observed when the stimulation amplitude was above 3 mA. The increase in esophageal pressure was associated with the amplitude of stimulus as well as the frequency. During stimulation, atropine, phentolamine and L-NAME had no effect on the increase of esophageal pressure induced by ES. These findings implied that ES induced esophageal contraction were not mediated via the NANC, adrenergic or cholinergic pathway. The amplitude of esophageal contraction was current and frequency dependent.

Pneumatosis intestinalis refers to lineal or cystic gas collections in the intestinal wall. Pneumatosis cystoides intestinalis (PCI) is a benign primary cause. This is a rare disease characterized by multiple gas cysts in the submucosa or subserosa, principally within the colon.

The digestive tract is a hollow tube consisting throughout of three coats or layers. The first layer, the mucosa, is made up of an epithelial lining which borders on the lumen of the bowel and rests upon a basement membrane, the lamina propria and the muscularis mucosae. The mucosa of the colon has a smooth surface and is composed of tubular parallel crypts embedded in a loosely arranged stroma. The mucosa of the ileum is composed of fingerlike villi and displays a number of specific features including the shorter villi and more epithelial goblet cells on the surface than the proximal small intestine and the presence of Peyer’s patches. The second coat is the submucosa. The muscularis propria, the third layer, is composed of two layers of smooth muscle separated by a thin layer of connective tissue in which the ganglionated myenteric plexus (Auerbach’s) can be observed. The subserosa is composed of loose areolar tissue covered by mesothelium where the tract borders on the body cavity (serosa). Endoscopic biopsies are limited to the mucosa and upper part of the submucosa. A good understanding of the normal histology of the mucosa and submucosa is essential for analysis of endoscopic biopsies of the ileum and the colon.

Summary An adult female California king snake (Lampropeltis getula californiae) housed in Taipei Zoo was presented with a 2-week history of anorexia, fatigue and abdominal swelling. Exploratory laparotomy revealed a gastric mass with two circular perforations and multiple mottled white to beige protuberances along the mucosal surface. Histologically, the gastric mass showed an invasive, transmural growth of epithelial cells arranged in nests, lobules, acini and sheets in the mucosa and submucosa that progressively transformed into signet ring cells in the muscularis externa and subserosa. All of the neoplastic cells expressed pan-cytokeratin immunohistochemically. Based on the World Health Organization histological criteria, a diagnosis of diffuse-type gastric mucinous and signet ring cell adenocarcinoma was made.

Lymph node (LN) metastasis of gastric cancer (GC) is the strongest prognostic indicator for this disease; however, the majority of the LN metastasis profiles of GC remain unknown, which notably hinders the therapeutic efficacy in clinic. In the present study, an orthotopic model of human GC was established for investigation of time-dependent LN metastasis patterns in mice. Luciferase-expressing NCI-N87 human GC cells were injected into the subserosa of the gastric body, resulting in a tumor formation rate of 100%. LN metastasis at four different anatomical positions in the abdomen were characterized until week 10 after tumor cell injection using sensitive bioluminescence imaging and histopathological analyses. Skip LN metastases were observed at later stages (weeks 8-10) of the experiment. Metastases in other major organs, including liver, spleen and lung, were also examined. Characterization of this orthotopic GC model and metastasis patterns in LNs and major organs should aid in the preclinical GC research regarding the metastatic mechanism and drug development.

Diffuse ganglioneuromatosis (DG) of the gastrointestinal tract is a rare condition that is closely associated with neurofibromatosis type 1 and multiple endocrine neoplasia type 2B. The occurrence of DG with multiple schwannomas, which, of the GI tract, usually affect the stomach, is considerably more rare. The present study describes the case of a 54-year-old male with indolent DG, principally involving the small intestine and colon, associated with multiple schwannomas in the subserosa. The patient was treated with surgery. A brief overview of intestinal ganglioneuromatous lesions and the associated conditions is additionally presented.

Background In animal studies, the inhibition of VEGF activity results in high mortality and impaired renal and glomerular development. Mechanical stimuli, like mechanical stretch in respiratory and circulatory systems, results in an elevated expression of VEGF. In animal models, the experimental urinary obstruction is associated with stretching of tubular cells and activations of the renin-angiotensin system. This results in the upregulation of vascular endothelial growth factor (VEGF) and TNF-alfa. Material/methods Tissue samples from urinary tract obstruction were collected and immunohistochemistry was performed in 14 patients (average age: 7.1±4.1 years). The control histology group consisted of ureteropelvic junction tissue from 10 fetuses after midtrimester artificial abortion. The fetuses did not have any failure at ultrasound screening and pathological examination. The mean gestational age was 20.6 weeks of gestation (±2.2SD). Expression of VEGF was detected with immunohistochemistry method. Results Expression of VEGF was found in varying intensity in the submucosa and subserosa layers, but only in the test tissue (placental tissue). The tissue of the patients with urinary obstruction and the tissue of the fetal ureteropelvic junction without urinary obstruction were negative for expression of VEGF. The repeated examination showed negative cells and no color staining. Conclusions The pressure due to congenital urogenital obstruction resulting in mechanical stress in cells did not increase the expression of VEGF in young children in our study. To find a correlation between urogenital tract obstruction and increased expression of VEGF, we need to perform more examinations because the connection may be of therapeutic significance.

The accessory liver lobe (ALL) of the gallbladder wall is rare, mentioned by Meckel since 1822. We present two cases of ALL occurring in two adult women. The ALLs were diagnosed at microscopic examination of cholecystectomy specimens for lithiasic cholecystitis and were located at the gallbladder body level. They measured 0.5 and 1.1 cm and were pediculated from the gallbladder serosa. Luschka duct complexes were seen in the adjacent subserosa in one of the cases. The main clinical relevance of ALL of the gallbladder resides in the differential diagnosis with a lymph node and in the risk of peroperative hemorragia or bile leakage by sectioning of the connecting blood vessels and/or bile duct. Intraparietal ALL may interfere with dysmotility, possibly resulting in bile stagnation and stone formation.

Background Primary colonic and dedifferentiated liposarcomas are both remarkably rare. This work describes a case of primary colonic well-differentiated/dedifferentiated liposarcoma and reviews the clinical characteristics and current therapies for liposarcoma tumors. Case presentation A 52-year-old woman was referred to our hospital with a submucosal tumor of the ascending colon. Clinical analysis by ultrasound colonoscopy and computed tomography revealed a partially ossified tumor with irregular edges continuous with the muscular layer. High F-18 deoxyglucose uptake was detected by positron emission tomography. Radical resection with lymph node dissection was performed, yielding a tumor specimen approximately 6.5 × 4.0 × 3.2 cm. Neoplastic spindle cell proliferation was found from submucosa to subserosa. Well-differentiated adipose tissue surrounded the tumor, but contained atypical nuclei with condensed chromosomes. Immunohistochemical staining was positive for p16, CDK4, and MDM2 expression. Based on these findings, a diagnosis of well-differentiated/dedifferentiated liposarcoma was given. Dedifferentiated liposarcomas are more aggressive than their well-differentiated, low-grade counterparts. While local recurrence can occur with both tumor types, dedifferentiated liposarcomas are more prone to developing distant metastases. The patient received no postoperative therapy, and no recurrences have been observed 12 months after surgery. Conclusions Here we report an extremely rare case of well-differentiated/dedifferentiated liposarcoma of the ascending colon. The dedifferentiated component was high-grade liposarcoma and well-differentiated liposarcoma was detected around the main tumor.

A granular cell tumor (GCT) is an uncommon mesenchymal lesion that rarely occurs in the colon and the rectum. We describe the case of 51-year-old man with a 2-cm-sized rectal GCT 10 cm above the anal verge that was incidentally detected after a screening colonoscopy. Preoperative radiologic studies demonstrated a suspicious submucosal rectal mass with mesorectal fat infiltration, but without circumferential resection margin threatening, extramural vessel invasion, and regional lymph-node enlargement. The tumor was resected by using a transanal endoscopic operation (TEO) without immediate postoperative complications. The final pathology revealed that the tumor consisted of a GCT that had invaded the subserosa with clear margins. It had no other risk factors for malignancy according to Fanburg-Smith criteria. We systematically reviewed the English literature by using PubMed and Google Scholar. This report may be the first documented case in the literature to describe a TEO for a GCT that had invaded the subserosa in the rectum.

The presence of well developed appendices in some animals when compared to humans has led to speculation that appendix is a vestigial organ. Increasing number of studies have revealed that the appendix serves as an important organ in humans. The function of animal appendix, and the differences between species remain poorly understood. In this study we examined human myenteric plexus and compared them with animal studies. Appendices were obtained from five young adults in which the appendix was found to be normal after removal. Fixed appendix cryosections were examined by immunofluorescence methods using neuronal marker antibodies to neurofilaments and beta III tubulin. Both antibodies stained myenteric ganglia which were arranged in an apparently irregular pattern in human appendix wall. We observed unexpected localization of myenteric ganglia in the subserosa often accompanied by rarely occurring ganglia in the longitudinal muscle layer. These ganglia were of different sizes and shapes and unequally distributed under a thin layer of serosa. Our findings raise many questions about the possible role of irregular and atypical myenteric ganglia localization in relation to altered motility and subsequent pathogenesis of the appendix in inflammatory disease in humans. On the other hand, studies of the literature have revealed simplicity in the organization of myenteric plexus, e.g., in well-developed rabbit appendix. In addition, appendicitis in animals is restricted to in apes with similarly shaped appendix to humans.

Objective: Colonic carcinomas spread to regional lymph nodes and liver. There are cancer-associated lymphatic and venous vessels at the margin of colonic carcinomas, which facilitate spreading carcinoma through lymphatic and venous vessels. This study aimed to examine cancer-associated lymphatic and venous vessels in TNM T1 to T3 carcinomas using lymphatic vessel hyaluronan receptor for lymphatic vessels and von Willebrand factor for venous vessels by immunocytochemical staining. Materials and Methods: A total of 40 cases of moderately differentiated colonic carcinoma were studied using routinely formalin-fixed and paraffin-embedded sections. The cases consisted of 10 cases of TNM T1, 15 cases each of T2 and T3 cases. Immunocytochemical staining was performed using goat antihuman LYVE-1for lymphatic vessels and rabbit antihuman von Willebrand factor for venous vessels. Results: In TNM T1 carcinoma, increased, irregular and narrow lymphatic and venous vessels were present in the adjacent normal mucosa to the carcinoma, some of which penetrated cancerous lesion. There were no tumor emboli in lymphatic and venous vessels. In TNM T2 carcinoma, there were few lymphatic and venous vessels in midst of the carcinoma whereas numerous small lymphatic and venous vessels were present within muscle layers adjacent to the invading carcinoma. Extramural tumor embolus was present in submucosa in one case. In TNM T3 carcinoma, cancer has invaded through the muscle layers where dilated lymphatic and venous vessels were present adjacent to cancerous nests. Tumor emboli were identified in two cases by immunocytochemical staining. Conclusion: The current study showed cancer-associated lymphatic and venous vessels at the interface in TNM T1 carcinoma to dilated intramuscular lymphatic and venous vessels adjacent to invading cancerous nests in TNM T3 carcinoma, and supports cancerous cells spread via lymphatic and venous vessels through muscle layers to subserosa as supported by tumor emboli in the lymphovascular system.