Biopsies Of Polyps Research Articles

Distal colonic polyps: immunohistochemical study of proliferation and apoptosis

Background. It’s well known that colonic polyps can be precursors of colorectal cancer. But exact immunohistochemical parameters, including proliferation and apoptosis levels of polyps’ cells, that may have prognostic value, still not known. Objective. To study the features of immunohistochemical expression of proliferation and apoptosis markers by distal colonic polyps’ cells. Methods. Pathomorphological and immunohistochemical studies of biopsies of distal colonic polyps from 30 patients (the age ranged from 41 to 83 years) were carried out. Results. Distal colonic polyps are characterized by the medium proliferation level of epithelial cells [Me=62.40% (48.65; 76.23) for adenomas, Me=26.23% (22.19; 48.88) for hyperplastic polyps], the low proliferation level of stromal cells [Me=2.94% (1.23; 4.35) for adenomas, Me=1.18% (1.10; 1.86) for hyperplastic polyps], the low p53 expression level of epithelial and stromal cells [Me=2.39% (1.58; 8.26) and Me=1.23% (0.72; 1.49) for adenomas’ cells, Me=0,00% (0,00; 1,47) and Me=0,00% (0,00; 0,05) for hyperplastic polyps’ cells], and also by the low apoptosis level of epithelial and stromal cells [Me=31.84CUOD (19.53; 42.34) and Me=43.87CUOD (25.47; 73.09) for adenomas, Me=16.99CUOD (11.86; 39.85) and Me=28.64CUOD (19.20; 30.71) for hyperplastic polyps]. There are direct correlations between the expression levels of proliferation and apoptosis markers and also the dysplasia grade of the distal colonic adenomas: between the Ki-67 expression levels of epithelial and stromal cells and also the dysplasia grade (γ=0.65 and γ=0.70, respectively), between the p53 expression level of epithelial cells and the dysplasia grade (γ=0.53), between the caspase-3 expression levels of epithelial and stromal cells and also the dysplasia grade (γ=0.80 and γ=0.63, respectively). Moreover, there are direct correlations between the expression levels of proliferation and apoptosis markers of distal colonic polyps’ epitheliocytes: between the Ki-67 and p53 expression levels (r=0.71 for adenomas, r=0.79 for hyperplastic polyps), between the Ki-67 and caspase-3 expression levels (r=0.61 for adenomas), between the p53 and caspase-3 expression levels (r=0.59 for adenomas, r=0.79 for hyperplastic polyps). Conclusion. These data indicate the close association between the processes of proliferation, accumulation of p53 protein, and apoptosis of the distal colonic polyps’ cells.

Clinical diagnosis and treatment of eosinophilic otitis media

Objective: Eosinophilic otitis media(EOM) is a rare,refractory otitis media.This article summarizes the clinical manifestations and diagnosis and treatment experience of EOM. Method: Retrospective analysis of 3 cases of EOM patients with medical history, clinical manifestations, and related auxiliary examinations.Discuss the EOM clinical features,diagnosis and treatment in conjunction with the literature. Result: The clinical features of 3 patients with EOM were summarized as: a large amount of yellowish white secretions or polyps formation, obvious itching symptoms; polyp biopsy showed a large amount of eosinophil infiltration;topical use of hormone-containing ear drops treatment is effective.Conclusion: EOM is a new type of chronic otitis media.It has characteristic clinical manifestations,a comprehensive treatment based on glucocorticoids should be given..

Juvenile polyposis syndrome: a case report with colorectal adenocarcinoma in a young patient

Juvenile polyposis syndrome (JPS) is an autosomal dominant condition associated with multiple hamartomatous polyps in the gastrointestinal tract. We report a case of a 34-year-old male with no prior medical history who presented to his general practitioner with back pain. Computed tomography scanning of the abdomen and pelvis identified a mass in the sigmoid colon. Endoscopic examination revealed multiple colorectal polyps as well as a sigmoid colon lesion. The histopathology of the polyp biopsies showed the typical characteristics of juvenile polyps. The sigmoid lesion was a poorly differentiated malignancy with morphology and an immunohistochemistry profile in keeping with a primary colonic adenocarcinoma. In summary, we describe the case of a young patient with histopathology consistent with JPS and colorectal cancer at a young age.

Akt and estrogen receptor expression in nasal polyps.

Nasal polyps (NP) is a common chronic inflammatory disease of the mucous membranes in the nose and paranasal sinuses. The underlying mechanisms of pathologic conditions to NP formation remains unclear. The aim of this study is to evaluate the expression of Akt and estrogen receptor (ER) in nasal polyps. We respectively obtained 20 nasal polyp tissue and 15 concha from patients undergoing endoscopic polyp biopsy and turbinate resection. All samples were fixed in 10% formalin for 24 h and embedding in paraffin was using routine protocol for histological prepation. Sections 5 μm thick were cut and stained H&E. Tissue samples were stained with anti-ER and anti-Akt primary antibody, ER and Akt were evaluated immunohistochemically. There is a relationship between the estrogen receptor and PI3K/Akt signaling pathway in malignansy. In this study, it showed the effect of estrogen on the activation of Akt signaling pathway in nasal polyps. Mann- Whitney-U test was applied to evaluate the statistical differences between nasal polyp and control group, (P < 0.05) was accepted as significant. In H&E stained sections we observed a lot of inflamatory cells and eosinophils in the mucosa, submucosal connective tissue and around the glandular epithelium in nasal polyps. The mucosa and submucosal connective tissue was seen normally in control group in H&E stained. We determined that ER and Akt were intensely expressed in nasal polyps. Expression is localized especially in epithelial and glandular epithelium cells and submucosal connective tissue. In contrast, expression of ER and Akt were mildly expressed in turbinate resection samples. The expression of ER and Akt might be important factors in nasal polyp pathogenesis and may shed new light on clinical approaches in nasal polyp treatment.

Peutz Jeghers syndrome presenting as intestinal obstruction with ileocolic intussusception: a rare presentation

Many cases of Peutz Jeghers Syndrome presenting as intestinal obstruction with intussusception at various levels were reported in literature. This is a case of a 35 years old male farmer who presented to our hospital with the chief complaints of brown coloured stools since one month, pain in lower abdomen and bleeding per rectum since one week. All the findings of the examination were suggestive of intestinal obstruction. Further confirmation was made by Abdominal sonography, Contrast Enhanced Computed Tomography of abdomen and Sigmoidoscopy with colonic polyp biopsy. After going through all the investigations, a clinical diagnosis of multiple intestinal polyposis with ileo-colic intussusception and small bowel obstruction was made. Right hemicolectomy with ileo-colic anastomosis was performed and the specimen was sent for histopathological examination. A final diagnosis of Peutz Jeghers Syndrome was made based on Histopathology. Post surgical prognosis was good and the patient was discharged after 13 days. A regular follow up was recommended.

Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size.

Chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilia is a disease of the upper respiratory tract for which few therapies are available. Because the oral investigational drug dexpramipexole serendipitously decreased blood eosinophils in amyotrophic lateral sclerosis studies, we assessed its safety, eosinophil-lowering activity, and preliminary clinical efficacy in patients with CRSwNP and eosinophilia. Sixteen subjects with CRSwNP, absolute eosinophil count (AEC) ≥ 0.300 × 109 /L, and polyp tissue eosinophils were evaluable for efficacy in a 6-month open-label, multi-center study of dexpramipexole 150 mg twice daily. The coprimary endpoints were change in AEC and change in total polyp score (TPS) from baseline to month 6, with additional clinical and histologic endpoints assessed. Thirteen of 16 subjects completed 6 months of dexpramipexole treatment. Geometric mean baseline AEC was 0.525 ± 0.465 eosinophils × 109 /L and decreased to 0.031 ± 0.019 after 6 months of dexpramipexole treatment, a 94% reduction (P < 0.001). Ten of 16 subjects had eosinophil counts reduced to ≤ 0.020 × 109 /L at month 6. In 12 subjects with nasal polyp biopsies at baseline and month 6, tissue eosinophils were reduced from a mean of 168 ± 134 to 5 ± 2 per high-power field (HPF) (P = 0.001), a 97% reduction from baseline. There was no significant reduction in TPS or improvement in other clinical endpoints. Dexpramipexole was well tolerated, with no drug-related serious adverse events. Dexpramipexole treatment produced profound eosinophil-lowering in peripheral blood and nasal polyp tissue. Despite the near-elimination of polyp eosinophils, decreased TPS and nasal symptom improvement were not observed. 2 Laryngoscope, 129:E61-E66, 2019.

A Case of Endoscopic Mucosal Resection of Gastric Metastasis From Renal Cell Carcinoma Without Recurrence

IntroductionRenal cell carcinoma (RCC) with gastric metastasis is extremely rare. The most common intervention is partial gastric resection; however, recently interventions including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) have been used. We present a case of gastric metastasis from RCC that was completely resected by EMR with pathology showing clear margins. Two year follow up showed no local recurrence or distal metastasis. Case Report A 86-year-old male with history of RCC PT2N0M0 diagnosed 8 years prior s/p partial right nephrectomy presented to the ED with exertional dyspnea. Patient had a hemoglobin of 7mg/dL. Emergent EGD revealed a single 25mm sessile polyp in the gastric fundus with stigmata of recent bleeding treated with epinephrine injection. Subsequently patient underwent repeat EGD and, in view of atypical nature, polyp biopsies were performed. Pathology showed inflammatory changes and no malignancy. Five days later, the patient underwent repeat EGD. The polyp was excised completely by standard EMR technique with methylene blue saline-lift. Pathology of the polyp showed metastatic clear cell renal carcinoma with clear cauterized margin. Follow-up EGDs performed at 10 days, 4, 9 and 22 months and EUS at 9 and 24 months post EMR showed no local recurrence. PET/CT at 15 and 24 months after EMR revealed no evidence of distal metastases. Discussion In a known RCC with gastric metastasis, EUS should be performed to evaluate the involvement of gastric layers. If the fourth layer (muscularis propria) is involved, partial gastrectomy is the preferred choice. Otherwise an ESD with en bloc excision is the best option. In our case, the initial biopsy report was negative for malignancy; therefore, an EMR was done. The polyp could be lifted well with injection of methylene blue saline (lift sign is the best marker that could be used for assessing excision of lesion by EMR) hence the polyp was resected completely with negative cauterized margins. Our close surveillance in the span of 2 years with no recurrence, makes our case of a gastric metastasis resected by EMR an effective endoscopic intervention.2127_A Figure 1. (A) A single 25 mm sessile polyp with stigmata of recent bleeding was found in the gastric fundus. (B) An EGD 5 days later showing 25 mm sessile polyp found on prior endoscopy (C) EGD s/p polypectomy via an EMR with complete resection and retrieval.2127_B Figure 2. (A) This is a H&E slide with 10x magnification. Superficial biopsy showing inflammatory changes, and granulation tissue. (B) H&E slide with 2X magnification showing metastatic RCC with well visualized cauterized resection with clear margins. Cauterized margin (blue arrows) is 1.5 mm away from closest metastatic RCC (asterisks). (C) H&E slide of the RCC with 10x magnification. (D) H&E slide with 40x magnification of RCC.2127_C Figure 3. Two year follow up EUS shows endoclip in the gastric fundus with intact fourth layer (muscularis propria) and no subepithelial lesion.

The gastric mucosal-associated microbiome in patients with gastric polyposis

The characteristics of the gastric microbiota in patients with gastric polyposis (GP) remain unclear. Given this we collected gastric antrum and gastric body biopsies from healthy controls (HC.A and HC.B group) and gastric antrum, gastric body and polyp biopsies from patients with multiple gastric polyps (GP.A, GP.B and GP.P group) for 16S rDNA sequencing. The results showed that the diversity of the gastric flora in the GP group was significantly lower than that of the HC group. The gastric flora composition of the GP group was significantly different from the HC group. However, flora diversity and compositions in different parts of the stomach (gastric antrum, gastric body or polyp tissue) were not significantly different. H. pylori abundance could influence the composition of gastric microbiota. Meanwhile, patients with fundic gland polyps (FGPs) and those with hyperplastic polyps (HPs) had considerably similar gastric bacterial compositions. We constructed a microbial dysbiosis index (MDI) based on the gastric microbiota at the genus level as a predictive model, and it was able to distinguish between individuals in the GP and HC groups. These findings showed that intragastric flora dysbiosis may be closely related to the occurrence and development of gastric polyps.

Expression of E-prostanoid receptors in nasal polyp tissues of smoking and nonsmoking patients with chronic rhinosinusitis.

BackgroundDifferent inflammatory reactions have been observed in the polyp tissues of nonsmokers and smokers with chronic rhinosinusitis (CRS). E-prostanoid (EP) receptors play a role in the inflammatory processes. Cigarette smoke (CS) exposure regulates EP-receptor expression levels promoting inflammatory mediator release from various inflammatory cells. In this study, we characterize the EP-receptor expression profiles in the polyps of nonsmoking and smoking CRS patients to explore the possible role of CS in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP).MethodsPolyp biopsies were obtained from 28 non-smoking and 21 smoking CRSwNP patients. Histopathological characteristics were observed under a light microscope. The prostaglandin E2 (PGE2), TNF-α, and IL-8 contents in polyp tissues were detected using enzyme-linked immunosorbent assay. Immunostaining was used to locate EP receptors in polyps. Messenger RNA and protein expression of EP receptors were examined using quantitative real-time polymerase chain reaction and Western blot, respectively.ResultsMore severe inflammatory reactions occurred in polyp tissues of smoking CRSwNP patients. The PGE2, TNF-α, and IL-8 in tissue homogenate levels were significantly higher in smoking CRSwNP patients than those in nonsmoking CRSwNP patients. Moreover, the distribution of each EP receptor subtype was similar in both groups. Compared with the EP-receptor expression in nonsmokers, messenger RNA and protein of EP2 and EP4 receptor were significantly down-expressed in smoking patients, but EP1 and EP3 receptors did not show significant differences.ConclusionCS exposure downregulates the expression levels of EP2 and EP4 receptors and stimulates the production of PGE2 and the proinflammatory cytokine IL-8 and TNF-α in polyp tissues of CRS patients. The down-expressed EP2 and EP4 receptors might be associated with severe inflammatory reactions in smoking CRSwNP patients.

Sustained secretion of immunoglobulin by long-lived plasma cells from human nasal biopsies

Abstract Background During secondary immune responses, plasma cell survival and antibody production is mediated by extrinsic factors provided by the local environment. It is unknown whether there are long-lived plasma cells (LLPCs) in the human nasal mucosa. Objective To identify LLPCs and characterize functionally specific survival niche in the human nasal mucosa. Methods Nasal polyp (NP) biopsies were used for ex vivo air-liquid interface culture. Protein levels of immunoglobulins in tissue homogenates were detected by Bio-Plex. The expression of LLPCs related markers including NGF, TrkA, P75, IL-6, APRIL, CD138, CD20, CD4, CD8, ECP, Bcl2, Ki-67, CD3 were detected by means of quantitative RT-PCR, immunohistochemistry (IHC) and ELISA. Results Using an ex vivo biopsies culture, we found sustained IgG, IgA, IgE, and IgM secretion &amp;gt;4 wk of culture. IL-6, APRIL NGF, TrkA, and P-75 were up-regulated in CRSwNP compared with controls by ELISA or IHC. We assessed TrkA+ cells, ECP+ eosinophils, and tryptase+ mast cells represent the major interstitial cell sources of NGF, while tryptase+ mast cells and CD138+ plasma cells represent the major sources for TrkA in CRSwNP by immunohistochemistry. We performed histological analysis of fresh nasal polyp tissues, and of tissue fragments harvested 10, 20, 32 days after cultured respectively and found that there’s a small portion of plasma cell in CRSwNP expressed Bcl2 pre- and post-culture. However, post-cultured plasma cells do not express Ki67. Conclusion This study demonstrates that the human nasal mucosa harbors a population of nonproliferating plasma cells that are instructed by the microenvironment for prolonged survival and Ab secretion.

Gastric Metastasis of an Ovarian Granulosa Cell Tumor Diagnosed in a Patient with Worsening Reflux

CASE REPORT A 60-year-old woman with a 2-year history of T1a NX M0 ovarian granulosa cell tumor (GCT) status post total abdominal hysterectomy with bilateral salpingo-oophorectomy presented with worsening reflux, abdominal pain, nausea, and loss of appetite. Esophagogastroduodenoscopy showed multiple gastric polyps with white tops and patches of necrotic appearing mucosa (Figure 1). Biopsy of the gastric polyps showed extensive surface ulceration and necrosis with associated atypical epithelioid and spindle cell proliferation (Figure 2). Although the immunohistochemical markers for sex cord-stromal tumors are negative, the histomorphology is similar to the patient's prior ovarian GCT (Figure 3). An extensive immunohistochemical marker panel performed to exclude the other common entities was negative. Thus, this most likely represents a metastasis from the ovarian GCT. Metastatic workup revealed bilateral metastatic pulmonary nodules, enlarged paraesophageal and paraaortic lymph nodes, and a brain metastasis. Patient was a poor surgical candidate and did not tolerate chemotherapy. Repeat imaging showed disease progression; she refused palliative chemoradiation and chose comfort measures.Figure 1.: Esophagogastroduodenoscopy shows multiple gastric polyps with white tops and patches of necrotic appearing mucosa.Figure 2.: Gastric polyp biopsy showing atypical epithelioid and spindle cell population.Figure 3.: Histomorphology of the gastric polyp showing (A) negative calretinin immunostain of prior tumor and (B) immunostain of present tumor.GCT is a rare sex cord-stromal tumor associated with low malignant potential.1 This tumor has a strong tendency for late recurrences, with an incidence of 25-30%, and is associated with a poor prognosis.1 Once the tumor recurs, it is fatal in 80% of cases. Most recurrences occur within 10 years after the initial diagnosis (median 4-5 years).1-4 Prognostic factors that affect the 5-year survival rate include tumor rupture, tumor stage, tumor mitotic rate, and residual disease. Common sites of metastasis are within the pelvis and the lower abdomen, with rare cases in the lung, liver, brain, bone, diaphragm, abdominal wall, and adrenal gland.1-3 Patients should be kept on a long-term follow-up protocol even if the primary tumor is occult.2 Patients with advanced metastatic GCTs are treated with aggressive surgical debulking and postoperative chemotherapy (platinum-based), especially in cases of widespread metastasis.4,5 DISCLOSURES Author contributions: J.S. Klair and K. Soota wrote the manuscript and reviewed the literature. A. Vidholia provided the pathology images and reviewed the literature. C.M. Berkowitz revised the manuscript. JS Klair is the article guarantor.

Gastric Metastasis of an Ovarian Granulosa Cell Tumor Diagnosed in a Patient with Worsening Reflux

CASE REPORT A 60-year-old woman with a 2-year history of T1a NX M0 ovarian granulosa cell tumor (GCT) status post total abdominal hysterectomy with bilateral salpingo-oophorectomy presented with worsening reflux, abdominal pain, nausea, and loss of appetite. Esophagogastroduodenoscopy showed multiple gastric polyps with white tops and patches of necrotic appearing mucosa (Figure 1). Biopsy of the gastric polyps showed extensive surface ulceration and necrosis with associated atypical epithelioid and spindle cell proliferation (Figure 2). Although the immunohistochemical markers for sex cord-stromal tumors are negative, the histomorphology is similar to the patient's prior ovarian GCT (Figure 3). An extensive immunohistochemical marker panel performed to exclude the other common entities was negative. Thus, this most likely represents a metastasis from the ovarian GCT. Metastatic workup revealed bilateral metastatic pulmonary nodules, enlarged paraesophageal and paraaortic lymph nodes, and a brain metastasis. Patient was a poor surgical candidate and did not tolerate chemotherapy. Repeat imaging showed disease progression; she refused palliative chemoradiation and chose comfort measures.Figure 1.: Esophagogastroduodenoscopy shows multiple gastric polyps with white tops and patches of necrotic appearing mucosa.Figure 2.: Gastric polyp biopsy showing atypical epithelioid and spindle cell population.Figure 3.: Histomorphology of the gastric polyp showing (A) negative calretinin immunostain of prior tumor and (B) immunostain of present tumor.GCT is a rare sex cord-stromal tumor associated with low malignant potential.1 This tumor has a strong tendency for late recurrences, with an incidence of 25-30%, and is associated with a poor prognosis.1 Once the tumor recurs, it is fatal in 80% of cases. Most recurrences occur within 10 years after the initial diagnosis (median 4-5 years).1-4 Prognostic factors that affect the 5-year survival rate include tumor rupture, tumor stage, tumor mitotic rate, and residual disease. Common sites of metastasis are within the pelvis and the lower abdomen, with rare cases in the lung, liver, brain, bone, diaphragm, abdominal wall, and adrenal gland.1-3 Patients should be kept on a long-term follow-up protocol even if the primary tumor is occult.2 Patients with advanced metastatic GCTs are treated with aggressive surgical debulking and postoperative chemotherapy (platinum-based), especially in cases of widespread metastasis.4,5 DISCLOSURES Author contributions: J.S. Klair and K. Soota wrote the manuscript and reviewed the literature. A. Vidholia provided the pathology images and reviewed the literature. C.M. Berkowitz revised the manuscript. JS Klair is the article guarantor.

Loss of epithelial markers is an early event in oral dysplasia and is observed within the safety margin of dysplastic and T1 OSCC biopsies.

Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer that is associated with poor 5-year patient survival. Disease treatment is further compounded by the difficulty in predicting pre-cancerous tissues that will progress to OSCC and the high recurrence rates following surgical resection. Here we have assessed expression of the oral epithelial markers E-cadherin, EMP1 and 5T4 and the pro-invasive N-cadherin proteins using fully characterised antibodies and quantitative immunofluorescence microscopy in normal tissue (NT), fibroepithelial polyp (FEP), low-grade dysplasia (LGD), high-grade dysplasia (HGD), T1 OSCC and T4 OSCC biopsies. Decreased E-cadherin expression was associated with FEP, LGD and HGD biopsies, demonstrating that loss of E-cadherin is an early event within abnormal epithelium and occurs in the absence of an E- to N-cadherin switch, the latter of which was only observed in T4 OSCC. Furthermore, loss of E-cadherin and EMP1 is an indicator of LGD (p = 0.0006) and loss of E-cadherin, EMP1 and 5T4 an indicator of HGD (p = 0.0006). Expression patterns of E-cadherin, EMP1 and N-cadherin could predict abnormal epithelium in LGD, HGD, T1 and T4 OSCC biopsies (z-value = 0 for all disease grades) and allowed classification of LGD (z = 1.47), HGD (z = 2.138), T1 (z = 1.05) and T4 OSCC (z = 1.49) biopsies. Therefore, these markers provide a useful means to predict abnormal epithelium in patient biopsies. Linear regression and coefficient of determination analysis revealed positive correlation with a NT>LGD>HGD disease transition but low correlation with a putative HGD>T1 OSCC>T4 OSCC disease transition. Furthermore, expression of E-cadherin, EMP1, 5T4 and N-cadherin in pathologically normal surgical safety margins of LGD, HGD and T1 OSCC patient biopsies revealed significant differences to NT and the use of safety margins or FEP as ‘normal tissue’ controls introduced Type II errors in all patient cohorts. This work forms the basis for further investigation of the role of E-cadherin loss in abnormal epithelium and in the development of automated analyses for use in cancer diagnostics.

Upregulation of Cystathionine-β-Synthase in Colonic Epithelia Reprograms Metabolism and Promotes Carcinogenesis.

The trans-sulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells. Differentially expressed metabolites (65 increased and 20 decreased) clustered into the glycolytic pathway, nucleotide sugars, intermediates of the pentose phosphate pathway, and lipogenesis, including primarily phospholipids, sphingolipids, and bile acids. CBS upregulation induced broad changes in the NCM356 cell transcriptome with over 350 differentially expressed genes. These genes overlapped significantly with gene sets related to glycolysis, hypoxia, and a colon cancer cell phenotype, including genes regulated by NF-κB, KRAS, p53, and Wnt signaling, genes downregulated after E-cadherin knockdown, and genes related to increased extracellular matrix, cell adhesion, and epithelial-to-mesenchymal transition. The CBS-induced switch to an anabolic metabolism was associated with increased NCM356 cell bioenergetics, proliferation, invasion through Matrigel, resistance to anoikis, and CBS-dependent tumorigenesis in immunocompromised mice. Genetic ablation of CBS in CBS heterozygous mice (CBS+/- ) reduced the number of mutagen-induced aberrant colonic crypt foci. Taken together, these results establish that activation of the CBS/H2S axis promotes colon carcinogenesis. Cancer Res; 77(21); 5741-54. ©2017 AACR.

A Rare Pancreatic Mass Diagnosed by Endoscopic Ultrasound-Guided Biopsy

Carcinosarcoma's are uncommon neoplasms primarily located in the uterus. Pancreatic carcinosarcoma is a more rare entity, generally identified in the middle aged or elderly. Histologically, pancreatic carcinosarcoma is characterized by carcinomatous and sarcomatous components. A small number of pancreatic carcinosarcoma has been reported in literature; for which the diagnosis was made via surgery. Prognosis of pancreatic carcinosarcoma is poor with average survival of 6 months. A 69-year-old female presented with cough and chest pain. She underwent CT chest, revealing pericardial effusion, pleural effusion, and pulmonary nodules. With concern for malignancy, patient underwent CT abdomen/pelvis, revealing heterogeneously enhancing mass in the genu of the pancreas. Laboratory studies were significant for CA 19-9 of 13.5 U/L, CEA of 0.7 ng/mL, aspartate aminotransferase of 16 U/L, alanine aminotransferase of 19 U/L, alkaline phosphatase of 119 U/L, and total bilirubin of 0.6 mg/dL. She underwent upper endoscopy and endoscopic ultrasound (EUS). Gastroscopy revealed ulcerated gastric polyps that were biopsied with cold forceps. EUS demonstrated a hypoechoic mass in the pancreatic genu measuring 3.1 x 2 cm with abutment of the portal vein. Fine needle biopsy was performed with a 22-gauge biopsy needle (Sharkcore, Medtronic, Minneapolis, MN) via a trangastric approach. An enlarged lymph node was also biopsied in the peripancreatic region. Pancreatic mass biopsy revealed carcinosarcoma, with gastric polyp and peripancreatic lymph node biopsies revealing identical morphology. Patient was offered chemotherapy for treatment, but given poor prognosis, opted for hospice. This case is unique in that only approximately 20 cases of pancreatic carcinosarcoma have been reported in literature and all were diagnosed following surgical resection. To our knowledge, this is the first case of pancreatic carcinosarcoma being diagnosed by EUS guided core biopsy. Previous studies have demonstrated over 90% sensitivity for diagnostic yield with either a 22 or 25-gauge EUS guided core biopsy. This case demonstrates the rapidly emerging role and diagnostic ability for initial EUS guided biopsy for solid neoplasms in lieu of fine needle aspiration. It also reaffirms the importance of obtaining a histologic diagnosis prior to surgical resection or chemotherapy.

Giant Fundic Gland Polyps in a Rare Disease

Our patient is a 39-yr-old previously healthy Hispanic female who complains of years of epigastric pain, acutely worsening over the past 2 weeks. She complained of 80lb weight loss, fatigue & intermittent diarrhea over the past 1.5 years. Otherwise review of systems was negative. Medications included omeprazole & ibuprofen prn. Family & social history were unrevealing. On physical examination, vitals were normal with palpable thyroid, mild tenderness over epigastrium with palpation. Lab tests revealed: Hemoglobin 2.1g/dL;hemocrit 8.7%. Multi-chemistry screen was remarkable for Ca 11mg/dL. EGD revealed multiple giant gastric polyps (15-40mm), thickened gastric folds without discrete mass or ulcerations (Figure 1&2). Histology of gastric polyp biopsies showed cystically dilated fundic glands lined by normal gastric epithelium, without evidence of dysplasia, consistent with fundic gland polyps. Colonoscopy was notable for a single diminutive tubular adenoma. Contrasted CT abdomen/pelvis was notable for a mass in the tail of pancreas measuring 1.6cm & portocaval mass measuring 7.8cm. Fasting serum gastrin level was >10000. EUS with FNA of pancreatic & portocaval mass/lymph node was performed with malignant cells of a well differentiated neuroendocrine tumor, low grade. Due to hyperparathyroidism, the patient underwent parathyroidectomy & partial thymectomy that revealed parathyroid adenoma. Our patient met criteria for multiple endocrine neoplasia type 1a with parathyroid tumor, metastatic pancreatic neuroendocrine neoplasm & Zollinger-Ellison syndrome. She was started on high-dose proton pump inhibitor & subcutaneous octreotide injections. Surgical oncology & tumor board consultation yielded decision to continue depot octreotide lifelong given metastatic disease. She underwent evaluation for pituitary tumors including prolactin & MRI of sella turcica, which were negative. Her epigastric pain & anemia improved on PPI and octreotide & will continue surveillance for pituitary tumors & GI tumor progression. Genetic testing revealed a pathogenic mutation in the MEN1 gene (c.1406_1413dupAGCCGTGG), confirming diagnosis of an index case of sporadic MEN1a. Detection of sporadic MEN1a requires a high degree of suspicion & should be considered in cases of epigastric pain, diarrhea with concomitant hyperparathyroidism. Previous association of giant fundic gland polyps & MEN1 has not been reported.Figure: Stomach.Figure: Giant fundic gland polyp.

Gastric Xanthoma (GX) as an Incidental Endoscopic Finding: A Report of 2 Cases

Gastric xanthomas (GXs) are yellow mucosal lesions characterized by the accumulation of lipid-laden histiocytes in the lamina propria. It is usually an incidental endoscopic finding of unclear clinical significance. It has a quite variable incidence that increases with age. GX was reported to be associated with chronic gastritis, hyperplastic polyps, gastric cancer and H.pylori infection. It has been hypothesized that GX could be related to gastric injury, which was supported by the higher prevalence of gastric atrophy among reported cases. Surprisingly, no correlation between GX and hyperlipidemia was found. Case 1: A 54 year-old Caucasian female with a history of primary pulmonary hypertension and ESRD post renal and bilateral lung transplant, admitted to the hospital with epigastric pain. Vital signs were normal, physical examination was significant for mild epigastric tenderness. Laboratory work and Imaging studies were inconclusive. EGD was remarkable for a single 5 mm sessile in the gastric fundus, complete resection was accomplished. (Figure 1) Pathology results revealed GX with focal active inflammation and erosion, No Helicobacter pylori organisms identified. There was no evidence of malignancy.FigureCase 2: This is an 82 year-old male with a significant history of DM II and renal cell carcinoma, who presented to our hospital with melena. On physical examination, he looked pale and tired. Vital signs were stable, his labs were remarkable only for normocytic anemia (HB: 7.9 g/dL, MCV: 92 fL). EGD was performed next day and it revealed a mass in the gastric body and a small gastric antral polyp (Figure 2), both biopsied. Subsequently, pathology results showed clear cell carcinoma consistent with metastatic renal cell carcinoma (the mass). Gastric antral polyp biopsy was suggestive of gastric xanthoma, confirmed by immunohistochemical staining for CD68. Eventually, laparoscopic partial gastrectomy was performed successfully. GX is a rare condition of unknown etiology, there is increasing evidence on the association between GX and gastric injury. GX should be considered as a warning sign, to look for other concomitant serious conditions, most importantly gastric cancer. In our reported cases, there was no evidence of H. pylori infection or primary gastric cancer, lipid profile was normal. However, the second patient endoscopy revealed a metastatic gastric mass. We think it is prudent to look for GX gastric partners and always send for histologic confirmation.Figure

Computed Tomography Score an Excellent Marker: Differentiates Eosinophilic and Non-eosinophilic Variants of Chronic Rhinosinusitis with Nasal Polyp.

Eosinophilic and non-eosinophilic subtypes of chronic rhinosinusitis with nasal polyp (CRSwNP) have different clinical profile and management. Currently the 2 subtypes are differentiated based on tissue eosinophilic infiltration, which is identified after surgery by histopathological examination. Hence this study was conducted to compare utility of computed tomography (CT) scans, serum IgE levels, absolute eosinophil count (AEC) and Sino-nasal Outcome Test (SNOT)-20 score for discriminating the 2 subtypes. In this prospective study of 1year duration, patients suspected of CRSwNP were recruited. Serum IgE levels and AEC estimation were performed by ELISA and standard numerical formula respectively, along with histopathological examination of nasal polyp biopsies. CT score and ratio of CT score for ethmoid sinus and maxillary sinus (E/M ratio) were calculated. Patients were asked to fill SNOT-20 questionnaire. Receiver-operating characteristic (ROC) curve analysis was performed. Out of 52 patients studied, 38 and 14 were no. of eosinophilic and non-eosinophilic CRSwNP cases respectively on the basis of histopathological examination. E/M ratio and overall CT score were found to be highly accurate with area under ROC curve of 0.990 and 0.964 respectively, while rest 3 parameters had low accuracy. Optimal cut-off of CT score and E/M ratio for eosinophilic CRSwNP were 6 and 2.065 respectively. This study demonstrated E/M ratio and total CT score as the most useful surrogate markers for preoperative differentiation of eosinophilic and non-eosinophilic CRSwNP, and hence can be used to predetermine postoperative management before surgery.

Polyp detection rate in transverse and sigmoid colon significantly increases with longer withdrawal time during screening colonoscopy.

BackgroundThe guidelines for colonoscopy present withdrawal time (WT) and adenoma detection rate (ADR) as the quality indicator. The purpose of this retrospective study is to analyze the predicting factors with polyp detection rate (PDR) as a surrogate for ADR by using comprehensive health checkup data, and assess the correlation between PDR per each colonic segment and WT, and factors influencing WT.MethodsOne thousand and thirty six consecutive health checkup cases from April 2015 to March 2016 were enrolled in this study, and 880 subjects who undertook colonoscopy without polyp removal or biopsy were divided into the two groups (polyp not detected group vs polyp detected group). The two groups were compared by subjects and clinical characteristics with univariate analysis followed by multivariate analysis. Colonoscopies with longer WT (≥ 6 min) and those with shorter WT (< 6 min) were compared by PDR per each colonic segment, and also by subjects and clinical characteristics.ResultsA total of 1009 subjects included two incomplete colonoscopies (CIR, 99.9%) and overall PDR was 35.8%. A multiple logistic regression model demonstrated that age, gender, and WT were significantly related factors for polyp detection (odds ratio, 1.036; 1.771; 1.217). PDR showed a linear increase as WT increased from 3 min to 9 min (r = 0.989, p = 0.000) and PDR with long WT group was higher than that with short WT group per each colonic segment, significantly in transverse (2.3 times, p = 0.004) and sigmoid colon (2.1 times, p = 0.001). Not only bowel preparation quality but also insertion difficulty evaluated by endoscopist were significant factors relating with WT (odds ratio, 3.811; 1.679).ConclusionThis study suggests that endoscopists should be recommended to take more time up to 9 min of WT to observe transverse and sigmoid colon, especially when they feel no difficulty during scope insertion.

Immunohistochemical Expression of the Tumor Suppressor Protein p16INK4a in Cervical Adenocarcinoma.

Objective To evaluate the diagnostic utility of the p16ink4a protein expression as a marker for adenocarcinoma of the cervix. Methods In a cross-sectional study, p16ink4a expression was evaluated in 30 cervical biopsies from patients diagnosed with invasive adenocarcinoma from 2 reference clinics in Brazil, and compared with 18 biopsies of endocervical polyps (control cases). The performance of the tests for p16ink4a was evaluated using a conventional contingency table, and the Kappa (κ) index was used to evaluate the agreement of the marker with the tissue diagnosis. Results In total, 66% of the invasive adenocarcinoma cases were positive for p16ink4a. All of the adenomatous polyps cases used as negative controls were shown to be negative for p16ink4a. The marker showed a high sensitivity and a high negative predictive value. The Kappa index was good for p16ink4a (κ = 0.6). Conclusion Considering the strong association between the p16ink4a marker and the cervical adenocarcinoma, its use represents an important tool for reducing incorrect diagnoses of adenocarcinoma and thereby avoiding overtreatment.