Prediction of celiac disease at endoscopy.

BACKGROUND AND STUDY AIMS: Celiac disease is increasingly recognized worldwide, but guidelines on how to detect the condition and diagnose patients are unclear. In this study the prevalence and predictors of celiac disease were prospectively determined in a cross-sectional sample of Lebanese patients undergoing esophagogastroduodenoscopy (EGD). PATIENTS AND METHODS: Consecutive consenting patients (n = 999) undergoing EGD answered a questionnaire and had blood taken for serologic testing. Endoscopic markers for celiac disease were documented and duodenal biopsies were obtained. The diagnosis of celiac disease was based on abnormal duodenal histology and positive serology. Risk factors were used to classify patients to either high or low risk for celiac disease. Independent predictors of celiac disease were derived via multivariate logistic regression. RESULTS: Villous atrophy (Marsh 3) and celiac disease were present in 1.8 % and 1.5 % of patients, respectively. Most were missed on clinical and endoscopic grounds. The sensitivity of tissue transglutaminase (tTG) testing for the diagnosis of villous atrophy and celiac disease was 72.2 % and 86.7 %, respectively. The positive predictive value of the deamidated gliadin peptide (DGP) test was 34.2 % and that of a strongly positive tTG was 80 %. While the strongest predictor of celiac disease was a positive tTG (odds ratio [OR] 131.7, 95 % confidence interval [CI] 29.0 - 598.6), endoscopic features of villous atrophy (OR 64.8, 95 %CI 10.7 - 391.3), history of eczema (OR 4.6, 95 %CI 0.8 - 28.8), anemia (OR 6.7, 95 %CI 1.2 - 38.4), and being Shiite (OR 5.4, 95 %CI 1.1 - 26.6) significantly predicted celiac disease. A strategy of biopsying the duodenum based on independent predictors had a sensitivity of 93 % - 100 % for the diagnosis of celiac disease, with an acceptable (22 % - 26 %) rate of performing unnecessary biopsies. A strategy that excluded pre-EGD serology produced a sensitivity of 93 % - 94 % and an unnecessary biopsy rate of 52 %. CONCLUSION: An approach based solely on standard clinical suspicion and endoscopic findings is associated with a significant miss rate for celiac disease. A strategy to biopsy based on the derived celiac disease prediction models using easily obtained information prior to or during endoscopy, maximized the diagnosis while minimizing unnecessary biopsies.

Transglottic basaloid squamous cell carcinoma of the larynx.

OBJECTIVE: To report a rare case of Transglottic Basaloid Squamous cell carcinoma of the larynx and review the pathologic features of these lesions. CASE REPORT: A 64 year old male, heavy smoker and alcohol abuser, presented with a 6 month history of hoarseness. Laryngoscopy revealed a right transglottic lesion involving the epiglottis, aryepiglottic fold, ventricle and true vocal fold. Microscopically, the tumor was characterized by infiltrating solid sheets of basaloid cells showing palisading pattern along the edges. In areas of solid growth, tumor cells displayed scant cytoplasm, and hyperchromatic nuclei. A portion of the tumor abutting the thyroid cartilage showed squamous differentiation. An island of tumor cells with comedonecrosis was also noted. Immunohistochemical staining for a number of markers was performed. CONCLUSION: Basaloid squamous cell carcinoma displays a biphasic histology. The stage of the disease at presentation is invariably advanced with metastatic lymphadenopathy in two thirds of the patients.

Biospecimen Repositories in Low- and Middle-Income Countries: Insights From an American University of Beirut and Memorial Sloan Kettering Collaboration.

PURPOSE: Biobanking helps source tissue and blood for studying cancer genomics. Access to biorepository resources in low- and middle-income countries is lacking. Memorial Sloan Kettering Cancer Center (MSK) and the American University of Beirut (AUB) established a joint tissue biorepository at AUB in Beirut, Lebanon. The undertaking encountered key challenges that were unanticipated. MATERIALS AND METHODS: Patients age 18 years or older were eligible for enrollment at AUB. After consent, biospecimens were obtained at the time of routine diagnostic and/or therapeutic interventions. Both normal and abnormal tissue and solid and/or liquid specimens were collected from varied body sites. Early on, declining consent was frequently observed, and this was highlighted for investigation to understand potential participants reasoning. RESULTS: Of 850 patients approached, 704 (70.8%) elected to consent and 293 (29.5%) declined participation. The number of declined consents led to an amendment permitting the documentation of reasons for same. Of 100 potential participants who declined to consent and to whom outreach was undertaken, 63% indicated lack of research awareness and 27% deferral to their primary physician or family member. A financial gain for AUB was cited as concern by 5%, cultural boundaries in 4%, and 1% expressed concern about confidentiality. Of the patients who elected to consent, 682 biospecimens were procured. CONCLUSION: The AUB-MSK biospecimen repository has provided a unique resource for interrogation. Patient participation rate was high, and analyses of those who elected not to consent (29%) provide important insights into educational need and the local and cultural awareness and norms.

Clinicopathologic and immunohistochemical characteristics of male breast cancer: a single center experience.

Male breast cancer (MaleBC) is a rare tumor that has been insufficiently described in the Middle East. The purpose of this study is to report the first MaleBC series in Lebanon, describing its clinicopathologic and immunohistochemical phenotype, and how it compares with MaleBC in the West and with female breast cancer in Lebanon and the Middle East. Forty-seven cases of MaleBC were reviewed. Results showed younger ages at presentation (62 years versus 67 years), higher incidence of lobular carcinoma (6% versus 1%), and more frequent p53 positivity and axillary node metastases in our series than in those reported about MaleBC. Other results such as higher estrogen receptor (ER) positivity and lower HER-2/neu over-expression were comparable to the literature. These findings suggest that MaleBC in our region may represent a biologically different tumor with potentially distinct prognostic and therapeutic implications.

Correlation of non-mass-like abnormal MR signal intensity with pathological findings surrounding pediatric osteosarcoma and Ewing's sarcoma.

OBJECTIVE: The aim of this work was to determine the role of MRI in interpreting abnormal signals within bones and soft tissues adjacent to tumor bulk of osteosarcoma and Ewing's sarcoma in a pediatric population by correlating MR findings with histopathology. MATERIALS AND METHODS: Thirty patients met the inclusion criteria, which included (1) osteosarcoma or Ewing's sarcoma, (2) MR studies no more than 2 months prior to surgery, (3) presence of abnormal MR signal surrounding the tumor bulk, (4) pathological material from resected tumor. The patients received standard neoadjuvant chemotherapy. Using grid maps on gross pathology specimens, the abnormal MR areas around the tumor were matched with the corresponding grid sections. Histopathology slides of these sections were then analyzed to determine the nature of the regions of interest. The MR/pathological correlation was evaluated using Mann-Whitney U test and Fisher's exact test. RESULTS: Twenty-seven patients had osteosarcoma and three patients had Ewing's sarcoma. Of the studied areas, 17.4% were positive for tumor (viable or necrotic). There was no statistically significant correlation between areas positive for tumor and age, gender, signal extent and intensity on MRI, or tissue type. There was, however, a statistically significant correlation between presence of tumor and the appearance of abnormal soft tissue signals. A feathery appearance correlated with tumor-negative areas whereas a bulky appearance correlated with tumor-positive regions. CONCLUSIONS: MR imaging is helpful in identifying the nature of abnormal signal areas surrounding bone sarcomas that are more likely to be tumor-free, particularly when the signal in the soft tissues surrounding the tumor is feathery and edema-like in appearance.

Role of Ultrastructural Study in the Diagnosis of Medical Renal Diseases: A Tertiary Medical Center Experience and Review of the Literature.

The 20th century unfolded many mysteries regarding renal pathology with the advent of ancillary techniques such as immunofluorescence (IF) and electron microscopy (EM) studies. EM plays a major role in confirming the routine and IF findings or may uncover new and unsuspected features. The aim of the study is to elucidate the role of ultrastructural findings in patients with medical kidney diseases on whom kidney biopsy was performed at the American University of Beirut Medical Center, between November 2018 and June 2019. A total of 188 renal biopsies were examined during the study period. EM confirmed the light microscopy diagnosis in 54% of the cases while completely changed the diagnosis in 23% of the cases. In 23% of the sample, EM provided additional features and a secondary diagnosis. Our study emphasizes the important diagnostic role of EM and its significance, particularly in minimal change disease, basement membrane abnormalities, and glomerulopathies.

CD147 Promotes Tumorigenesis via Exosome-Mediated Signaling in Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is an aggressive childhood soft-tissue tumor, with propensity for local invasion and distant metastasis. Exosomes are secreted vesicles that mediate paracrine signaling by delivering functional proteins and miRNA to recipient cells. The transmembrane protein CD147, also known as Basigin or EMMPRIN, is enriched in various tumor cells, as well as in tumor-derived exosomes, and has been correlated with poor prognosis in several types of cancer, but has not been previously investigated in RMS. We investigated the effects of CD147 on RMS cell biology and paracrine signaling, specifically its contribution to invasion and metastatic phenotype. CD147 downregulation diminishes RMS cell invasion and inhibits anchorage-independent growth in vitro. While treatment of normal fibroblasts with RMS-derived exosomes results in a significant increase in proliferation, migration, and invasion, these effects are reversed when using exosomes from CD147-downregulated RMS cells. In human RMS tissue, CD147 was expressed exclusively in metastatic tumors. Altogether, our results demonstrate that CD147 contributes to RMS tumor cell aggressiveness, and is involved in modulating the microenvironment through RMS-secreted exosomes. Targeted inhibition of CD147 reduces its expression levels within the isolated exosomes and reduces the capacity of these exosomes to enhance cellular invasive properties.

Thymoquinone Radiosensitizes Human Colorectal Cancer Cells in 2D and 3D Culture Models.

Resistance of cancer cells and normal tissue toxicity of ionizing radiation (IR) are known to limit the success of radiotherapy. There is growing interest in using IR with natural compounds to sensitize cancer cells and spare healthy tissues. Thymoquinone (TQ) was shown to radiosensitize several cancers, yet no studies have investigated its radiosensitizing effects on colorectal cancer (CRC). Here, we combined TQ with IR and determined its effects in two-dimensional (2D) and three-dimensional (3D) culture models derived from HCT116 and HT29 CRC cells, and in patient-derived organoids (PDOs). TQ sensitized CRC cells to IR and reduced cell viability and clonogenic survival and was non-toxic to non-tumorigenic intestinal cells. TQ sensitizing effects were associated with G2/M arrest and DNA damage as well as changes in key signaling molecules involved in this process. Combining a low dose of TQ (3 µM) with IR (2 Gy) inhibited sphere formation by 100% at generation 5 and this was associated with inhibition of stemness and DNA repair. These doses also led to ~1.4- to ~3.4-fold decrease in organoid forming ability of PDOs. Our findings show that combining TQ and IR could be a promising therapeutic strategy for eradicating CRC cells.

Establishment and characterization of prostate organoids from treatment-naïve patients with prostate cancer.

Three-dimensional (3D) organoid culture systems are emerging as potential reliable tools to investigate basic developmental processes of human disease, especially cancer. The present study used established and modified culture conditions to report successful generation and characterization of patient-derived organoids from fresh primary tissue specimens of patients with treatment-naïve prostate cancer (PCa). Fresh tissue specimens were collected, digested enzymatically and the resulting cell suspensions were plated in a 3D environment using Matrigel as an extracellular matrix. Previously established 12-factor medium for organoid culturing was modified to create a minimal 5-factor medium. Organoids and corresponding tissue specimens were characterized using transcriptomic analysis, immunofluorescent analysis, and immunohistochemistry. Furthermore, patient-derived organoids were used to assess the drug response. Treatment-naïve patient-derived PCa organoids were obtained from fresh radical prostatectomy specimens. These PCa organoids mimicked the heterogeneity of corresponding parental tumor tissue. Histopathological analysis demonstrated similar tissue architecture and cellular morphology, as well as consistent immunohistochemical marker expression. Also, the results confirmed the potential of organoids as an in vitro model to assess potential personalized treatment responses as there was a differential drug response between different patient samples. In conclusion, the present study investigated patient-derived organoids from a cohort of treatment-naïve patients. Derived organoids mimicked the histological features and prostate lineage profiles of their corresponding parental tissue and may present a potential model to predict patient-specific treatment response in a pre-clinical setting.

Novel therapeutic diiminoquinone exhibits anticancer effects on human colorectal cancer cells in two-dimensional and three-dimensional in vitro models.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Cancer stem cells (CSCs) in CRC, which are spared by many chemotherapeutics, have tumorigenic capacity and are believed to be the reason behind cancer relapse. So far, there have been no effective drugs to target colon CSCs. Diiminoquinone (DIQ) has shown promising effects on targeting colon cancer. However, there is limited research on the effects of DIQ on eradicating CSCs in CRC. AIM: To investigate the anticancer potential of DIQ on colon CSCs in two-dimensional (2D) and three-dimensional (3D) models using colonospheres and patient-derived organoids. METHODS: Various 2D methods have been used to assess the effect and the mechanism of DIQ on HCT116 and HT29 cell lines including cell proliferation and viability assays, migration and invasion assays, immunofluorescence staining, and flow cytometry. The potency of DIQ was also assessed in 3D culture using the sphere formation assay and colon cancer patient-derived organoid model. RESULTS: Our results showed that DIQ significantly inhibited cell proliferation, migration, and invasion in HCT116 and HT29 cell lines. DIQ treatment induced apoptosis along with an accumulation of HCT116 and HT29 cancer cells in the sub-G1 region and an increase in reactive oxygen species in both CRC cell lines. DIQ reduced sphere-forming and self-renewal ability of colon cancer HCT116 and HT29 stem/progenitor cells at sub-toxic doses of 1 µmol/L. Mechanistically, DIQ targets CSCs by downregulating the main components of stem cell-related -catenin, AKT, and ERK oncogenic signaling pathways. Potently, DIQ displayed a highly significant decrease in both the count and the size of the organoids derived from colon cancer patients as compared to control and 5-fluorouracil conditions. CONCLUSION: This study is the first documentation of the molecular mechanism of the novel anticancer therapeutic DIQ via targeting CSC, a promising compound that needs further investigation.

Intestinal polypoid arteriovenous malformation: unusual presentation in a child and review of the literature.

AIM: We report a jejuno-jejunal intussusception with a polypoid arteriovenous malformation as a lead point in a 12-year-old boy, presenting with lower abdominal pain and non-bloody non-projectile vomiting. METHODS: A computed tomography scan of the abdomen and pelvis showed proximal jejuno-jejunal intussusception in the right upper quadrant. Exploratory laparotomy revealed a 5.5 × 2.5 × 2 cm polypoid mass within the wall of the jejunum. Consequently, jejunal segment resection was performed with end to end jejunostomy. Our case is distinctive because it involves a rare vascular lesion at an atypical site, the jejunum, in a child with an unusual presentation of intussusception treated surgically. CONCLUSION: Many paediatric benign and surgical conditions present with similar clinical symptoms; the physician in the emergency department should try to narrow the differential diagnosis and recognize surgical emergencies to avoid any delay in intervention that could be life-threatening.

Prevalence and characteristics of post-gastroscopy gastric cancer: A retrospective study from an academic medical center.

BACKGROUND AND STUDY AIMS: Gastric cancer is diagnosed by endoscopy but false negative rates of up to 10% in the west and 40% in Asia have been reported. In Lebanon, little is known about the rates of post-gastroscopy gastric cancer (PGGC), defined as the proportion of patients diagnosed with gastric cancer with a negative previous examination within 2 years of diagnosis. We aimed to examine the rate of PGGC and its risk factors, clinico-pathologic and endoscopic characteristics at a University medical Center. PATIENTS AND METHODS: Retrospective analysis of patients with histologically proven gastric malignancy over the last 14 years. Patients with history of upper endoscopy preceding the index diagnostic endoscopy by 6 to 24 months were included. RESULTS: 18,976 patients underwent upper endoscopy and gastric cancer was diagnosed in 323 (1.7%). Of those, only 4 (1.2%) had a preceding endoscopy within 6 to 24 months of diagnosis: 3 adenocarcinoma and one MALT lymphoma. Upon review of the initial endoscopy, a mucosal abnormality had been noted in all 4 patients and biopsies taken in 3 were negative for cancer. The mean time to cancer diagnosis was 8 months (range 6-13 months). CONCLUSION: A small proportion of gastric carcinomas are missed on endoscopy in this study. Patients with endoscopic evidence of mucosal abnormalities and negative biopsies should undergo repeat examination with multiple biopsies. Proper endoscopic technique, lesion recognition and adoption of performance improvement measures are important to optimize endoscopic practice.

An Unusual Gastric Polyp: Brunneroma.

Brunneromas or polypoid hamartomas are benign lesions arising from Brunner glands. They are usually benign lesions with low potential for malignancy. They are usually located in the duodenum and manifest with different unspecific symptoms, such as abdominal pain, nausea, or bloating. Other more serious manifestations are also reported in the literature that are related to the size of the lesion. Usually, they are treated with endoscopic resection, with some lesions requiring surgical intervention. We present a case of a gastric antral polypoid lesion that was consistent with Brunneroma on histology.

Extraskeletal Ewing sarcoma: Diagnosis, management and prognosis.

Extraskeletal Ewing sarcoma (EES) is a relatively uncommon primary tumor of the soft tissues, which accounts for 20-30% of all reported cases of ES. Being uncommon, all members of the ES family tumors are treated following the same general protocol of sarcoma tumors. The present review summarizes the diagnosis, management and prognosis of EES, focusing on the differences between the subtypes of ESS. The clinical features and imaging of EES are also discussed. Magnetic resonance imaging is the modality of choice for diagnostic imaging and local staging, while core-needle biopsy with pathological testing is used to obtain a definitive diagnosis. Although several oncology groups endorse that ES family of tumors should be treated with similar algorithm and protocols, some studies have demonstrated that surgery and radiotherapy may be used as a form of local control. However, further studies are required to conclude the optimum treatment option for EES.

Positive predictive value of fecal immunochemical test for high-risk colonic adenomas and carcinoma: A health maintenance organization cohort screening study in Lebanon.

BACKGROUND AND STUDY AIMS: Fecal Immunochemical Test (FIT) is one of the leading modalities for colorectal cancer screening. Studies show that FIT is highly sensitive for the detection of colorectal cancer (CRC) but not similarly accurate for detection of pre-cancerous advanced adenomas (AA). We studied the performance metrics of FIT for the detection of CRC and AA in ahealth maintenance organization (HMO) cohort screening program. PATIENTS AND METHODS: Retrospective cohort study of asymptomatic persons of screening age belonging to a HMO. Endoscopy and pathology reports of those who tested positive were used to calculate the positive predictive value (PPV) of FIT, and characterize endoscopic findings on colonoscopy. RESULTS: Between 1995 and 2017, 3000 persons had screening fecal occult testing as part of their Employee Health Care plan. Of those, 150 had a positive qualitative FIT (cutoff 10 Âµg hemoglobin/g feces). All underwentcolonoscopy, and median time to colonoscopy was 27 days. 4 (2.6%) had carcinoma(2 stage IIIA and 2 stage IIIB), 106 (70.6%) had adenomas of which 40 (26.6% of the total cohort) had advanced adenomas (≥1 cm, villous features, or high-grade dysplasia) giving a PPV for AA and carcinoma of 29% and 3% respectively. When stratified by age, the PPV of AA; carcinoma was [50-59 (21.7%; 0.0%)], [60-69 (14.6%; 4.2%)], [70-79 (42.6%; 2.1%)], [80-89 (33.3%; 11.1%)]. CONCLUSION: The performance characteristics of FIT testing are acceptable for population screening in resource-limited settings. The resultsof this study are helpful when discussing expectations prior to colonoscopy in people with positive FIT.

Successful treatment of severe retro-peritoneal bleeding with recombinant factor VIIa in women with placenta percreta invading into the left broad ligament: unusual repeated ante-partum intra-abdominal bleeding.

We experienced unusual repeated ante-partum intra-abdominal bleedings in a woman with placenta percreta invading into the left broad ligament, in whom recombinant factor VIIa was effective for controlling severe retro-peritoneal bleeding. A 34-year-old multiparaous woman with two prior cesarean sections presented acute abdominal pain at 16 weeks of gestation. She also represented with abdominal pain at 22 weeks of gestation, and a diagnostic laparoscopy revealed hemoperitoneum, although we could not identify the exact source of bleeding. She also represented with abdominal pain without vaginal bleeding at 27 weeks of gestation, and an MRI revealed a hematoma in the lower abdomino-pelvic region and placenta percreta invading into the left broad ligament. A classical cesarean section followed by hysterectomy with partial cystectomy was performed at 32 weeks of gestation. Since the bleeding from the retro-peritoneum could not be controlled by the use of fresh frozen plasma, recombinant factor VIIa was administered, resulting in successful hemostasis.

Tracheal schwannoma: a misleading entity.

Primary tracheal tumors are rare with the majority being malignant. Benign lesions are less frequent with primary tracheal schwannomas accounting for less than 0.5% of tracheal tumors. They are more common in females and their clinical presentation is non-specific. Chronic cough, progressive respiratory distress and even asthma-like conditions prevail as presenting symptoms and signs. Laryngotracheal endoscopy reveals a solitary, well encapsulated mass arising most often from the posterior tracheal wall. The diagnosis of tracheal schwannomas is primarily pathological. Endoscopic excision, sleeve excision or tracheal resection, are all commonly accepted treatment modalities. Proper awareness of these lesions is crucial in the pre-operative work-up of patients presenting with stridor.

Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer.

BACKGROUND: The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis. METHODS: We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph node-positive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (< .25, .25-.49, .50-.74, .75-1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS. RESULTS: On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of >or= .25. CONCLUSIONS: Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Unique Presentation and Management Approach of Pleural Solitary Fibrous Tumor.

Solitary fibrous tumor (SFT) of the pleura is an uncommon tumor that is often discovered incidentally on a routine chest X-ray. We report a case of a young female with a large, sessile, hypervascularized SFT of the pleura presenting with cardiopulmonary shock to a rural hospital with limited therapeutic interventions. We propose, in this case report, a unique multidisciplinary approach for the management of such a critical patient and the safe resection of the tumor.