Intestinal-type Adenocarcinoma Research Articles

Abstract 2125: Genetic analysis for classification and treatment of poorly differentiated sinonasal cancer

Abstract Introduction: The sinonasal cavities harbour a wide variety of rare tumour types, including squamous-cell carcinoma (SNSCC), intestinal-type adenocarcinoma (ITAC), olfactory neuroblastoma (ONB), neuroendocrine carcinoma (SNEC), undifferentiated carcinoma (SNUC) and malignant mucosal melanoma (MMM). Histopathological classification is related to clinical outcome, but correct diagnosis is difficult in cases with poor differentiation. Five-year overall survival ranges from 20% to 60% while therapeutic options are limited. This study aims to identify genetic alterations that may aid diagnosis and indicate targets for modern specific therapies. Experimental procedures: DNA was extracted from 80 frozen or paraffin-embedded tumor tissues collected from three different hospital centers. Mutations were screened by next generation sequencing of a panel of 120 cancer-related genes using the SureSelect QXT Target Enrichment Kit for Ilumina Multiplexed Sequencing, and recurrent hits were confirmed by Sanger sequencing and by analyzing their effect on protein expression. Results: Frequently mutated genes were TP53, KRAS, PI3K, NTRK1, ATM and BRCA1 and BRCA2. Several mutations were found exclusive to only one sinonasal tumor-type: APC and B-catenin in ITAC, EGFR exon 20 in SNSCC, IDH2 in SNUC and NF1 in MMM. With exception of ONB, a majority of cases showed a high mutational burden. Conclusions: A number of tumor-specific mutations were identified that may be used for differential diagnosis. In addition, many gene mutations may serve as targets for specific antibody or small molecule inhibitors. Finally, the finding that sinonasal tumors carry a high mutational burden suggests that therapy with immune checkpoint inhibitors may be effective in clinical management. Citation Format: Mario Hermsen, Cristina Riobello, Virginia N. Cabal, Rocío García-Marín, Sira Potes-Ares, Laura Suárez-Fernández, Blanca Vivanco, Alessandro Franchi, Reinhard Büttner, Fernando López, José Luis Llorente. Genetic analysis for classification and treatment of poorly differentiated sinonasal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2125.

Abstract 2132: Next generation sequencing for screening of clinically actionable mutations in intestinal-type sinonasal adenocarcinoma

Abstract Introduction: Sinonasal ITAC is a rare tumor commonly related to occupational wood or leather dust exposure. Clinical management has improved,however, recurrences are frequent, and the overall 5-year survival rateremains poor (60%). Therefore, there is a clear need for new therapeutic options. The aim of this study was to identify genetic alterations as specific targets for personalized treatment. Experimental procedures: Next Generation Sequencing using SureSelect QXT (Ilumina) was performed on a panel of 120 genes against which drugs have been approved by the FDA. Tumor and germline DNA of 25 patients was sequenced, for one case also the recurrence and metastasis. Pools were sequenced in a MiSeq system with a minumum coverage of 500X. To select somatic and pathogenic variants, the raw sequencing data were manually curated as follows: all silent mutations and variants with allele frequency >5% were discarded, only variants with tumor frequency >10 % of readings were considered; by comparing with the germline sample, only variants that appeared exclusively in the tumor sample were selected, as well as homozygous changes in the tumor that were heterozygous in the germline. Results: Five tumors (20%) did not show any somatic alteration in the 120 genes tested.In the remaining 20 tumors, mutations were found in 33 genes. The most relevant were involved in the EGFR-PI3K-AKT-MTOR, the MAPK-ERK and the Wnt signaling pathways, indicating an important role in ITAC tumorigenesis. The most frequently affected genes were tyrosin-kinase receptors (44%), especially the ERBB family (20% of cases with mutations) and FGFR1 (20% of tumors with gene copy number amplifications). Thirty-six percent and 28% of tumors showed alterations in the MAPK-ERK and PI3K-AKT-MTOR cascades respectively. PI3K mutations were particulary frequent (7 different variants in 5 tumors.) With regard to the Wnt pathway, both APC and CTNBB1 genes appeared mutated in 3 cases. In one patient, the primary tumor, recurrence and lymph node metastasis were investigated. All somatic alterations observed in the primary tumor (mutations in ATM, BRC2, KMT2B and amplifications of MET, ATM and FGF1R) remained present in both recurrence and metastasis, excluding the possibility of a second primary tumor. Additional mutations in the recurrence (NTRK1, TSC2 and PIK3R2) were also seen in the metastasis, while no alterations occurred in the metastasis exclusively. Confirmatory studies are underway correlating the most relevant sequencing results with gene and protein expression data of the affected pathways. Conclusions: By sequencing 120 clinically actionable genes in ITAC, several alterations were found that could be used as targets for new, personalized therapies. Examples include Dovitinib against FGFR1 amplification, antibody and small molecule inhibitors of ERBB, BRAF and MTOR, and tankyrase inhibitors targeting the Wnt pathway. Citation Format: Cristina Riobello, Virginia N. Cabal, Paula Sánchez Fernández, Rocío García-Marín, Blanca Vivanco, Fernando López, José L Llorente, Mario Hermsen. Next generation sequencing for screening of clinically actionable mutations in intestinal-type sinonasal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2132.

Immunohistochemical profiling of mucins in sinonasal adenocarcinomas

In this study we investigated the expression of mucins (MUC1, MUC2, MUC4, MUC5AC and MUC6) in a series of 66 sinonasal adenocarcinomas, in order to establish their distribution and the possible correlation with clinicopathological and prognostic parameters. The series included 51 intestinal type adenocarcinomas, 4 non-intestinal type adenocarcinomas, and 11 salivary gland type carcinomas. The immunohistochemical analysis was conducted on a tissue microarray obtained from formalin fixed-paraffin embedded tumor tissue samples. Thirty-nine adenocarcinomas (59.1%) resulted positive for MUC1, 21 (41.2%) for MUC2, 47 (71.2%) for MUC4, and 16 (24.2%) for MUC5AC, while MUC6 was negative in all cases tested. MUC1 was significantly more expressed in ITACs than in non-ITACs (70% vs 20%, p = 0.0007) while MUC2 was expressed only in ITACs (p = 0.0015) with a clear prevalence in the mucinous subtype (p < 0.0001). Conversely, MUC4 and MUC5AC were similarly expressed in the sinonasal adenocarcinoma subtypes tested. High expression of MUC 1 was related to a significantly shorter overall survival, both in the whole series (p = 0.04), while adenocarcinomas positive for MUC 2 tended to have a worse overall survival (p = 0.07). In addition, MUC2 expression was higher in ITACs with distant metastasis, being expressed in 4 out of 5 cases (p = 0.015). We conclude that sinonasal adenocarcinomas have a characteristic expression of different mucin types, with significant clinicopathologic correlations. In view of the extensive involvement of mucins in different aspects of tumor growth and their emerging role as possible therapeutic targets, our study suggests that these factors could be considered clinically relevant biomarkers and attractive targets for new treatments in sinonasal adenocarcinomas.

Full-body vibration effects on thermography in horses

Few studies in the literature take into account the WHO’s 2014 redefinition of the characteristics of mucinous adenocarcinoma of the uterine cervix. Our objective was to describe the characteristics of a group of these patients.This was a retrospective descriptive study of patients diagnosed between 1 January 2005 and 31 May 2016 in three hospitals in Lyon, France. All the cases of cervical adenocarcinoma were reanalysed by an expert in gynaecological pathology to retain the mucinous subtypes as defined in the 2014 WHO classification. We analysed their clinical and pathological characteristics.Among the 82 cases of cervical adenocarcinoma, 21 (26%) were diagnosed as mucinous. Ten were gastric type, of which four were in the extremely well differentiated form of minimal deviation adenocarcinomas, six were intestinal type, two were signet-ring cell type, and three were not otherwise specified. The patients’ mean age was 42 years and 18 patients were premenopausal. The revealing symptom was metrorrhagia in eight cases (38%) and mucinous vaginal discharge in four (19%). Fifteen (72%) of the cervical smear were abnormal. Five (31%) of the 16 patients with gastric or intestinal type adenocarcinoma had a specific radiological presentation: multiple cysts of the uterine isthmus, visible on ultrasound and with T2 hyperintensity on MRI.Mucinous adenocarcinoma is a rare form of cervical cancer that can be confused with other pathological types. It can be detected using cervical smears and should be suspected in cases of mucinous discharge and characteristic MRI features.

HER2 status in sinonasal intestinal-type adenocarcinoma

Given that the prognosis of patients with sinonasal intestinal-type adenocarcinoma (ITAC) has not significantly changed recently, there is a desire for new therapeutic approaches to improve clinical management. HER2-targeted therapy has remarkably improved the overall survival of patients with HER2 amplified tumors. To date, HER2 assessment has produced contradictory results in ITAC. The aim of this study was to assess HER2 status at both protein and DNA levels in a large series of ITAC. HER2 status was assessed by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in forty-three patients that underwent surgical resection for ITAC at the Otorhinolaryngology Section, Padua University Hospital, between 2007 and 2016. IHC was evaluated using the four-tier score developed for gastroesophageal cancer. As for IHC, 83.7% (36/43) of ITAC were scored 0, 14% (6/43) 1+, and 2.3% (1/43) 2+. No HER2 amplification was detected by CISH. The present is the largest study of sinonasal ITAC tested with both IHC and CISH confirmation for HER2 status. No HER2 overexpression/amplification was detected. Contrary to previous studies, our findings seem to rule out any oncogenetic role of HER2 in ITAC pathogenesis.

Septal Flip Flap for Anterior Skull Base Reconstruction After Endoscopic Transnasal Craniectomy: Long-Term Outcomes

Endoscopic endonasal anterior skull base malignant sinonasal tumor resection and reconstruction remains a challenge. We describe our septal flip flap (SFF) reconstruction, a new surgical technique for repairing anterior skull base defects and report our outcomes. We retrospectively reviewed the clinical data of 24 patients who underwent skull base reconstruction using a SFF following endoscopic resection with transnasal craniectomy. We raise the SFF from the contralateral nasal septum based on the septal branches of the anterior and posterior ethmoidal arteries; the SFF is then rotated laterally for anterior skull base reconstruction after transnasal resection with craniectomy. The SFF was used for multiple tumor types including, most commonly, intestinal-type adenocarcinoma, followed by olfactory neuroblastoma, squamous cell carcinoma, sinonasal undifferentiated carcinoma, and other types. All of the cases had either preoperative or postoperative radiation therapy. All flaps remained viable postoperatively. Postoperatively, nasal crusting was significantly reduced with faster healing of the surgical cavity. The SFF adds to the clinical armamentarium the opportunity to provide vascularized mucosal coverage extending from the frontal recess back to the planum sphenoidalis. The use of SFF requires careful consideration when dealing with paranasal sinus cancers so as not to infringe oncologic principles.

RHOA mutations and CLDN18-ARHGAP fusions in intestinal-type adenocarcinoma with anastomosing glands of the stomach

A subtype of intestinal-type adenocarcinoma of the stomach, characterized by low-grade cytological atypia and anastomosing glands, has been described in several reports under different names. One of the remarkable features of these lesions, herein referred to as intestinal-type adenocarcinoma with anastomosing glands, is the frequent association of poorly differentiated adenocarcinoma components. Here we analyzed 44 intestinal-type adenocarcinomas with anastomosing glands focusing on the molecular abnormalities that are common in diffuse-type gastric cancers. Next-generation sequencing identified RHOA and CDH1 mutations in 22 (50%) and one lesion (2%), respectively. Reverse transcription-PCR detected CLDN18-ARHGAP fusions in three lesions (7%). Immunohistochemically, none of the lesions showed abnormal p53 expression patterns whereas focal and diffuse loss of ARID1A was observed in four and one lesion, respectively. Examination of 37 lesions of dysplasia and 26 usual-type intramucosal adenocarcinomas identified one RHOA mutation in adenocarcinoma and no CLDN18-ARHGAP fusions, indicating that these genetic alterations are highly specific to intestinal-type adenocarcinomas with anastomosing glands among differentiated-type intramucosal neoplasms. The present study showed that intestinal-type adenocarcinoma with anastomosing glands represents a genetically distinct group of tumors with the frequent presence of RHOA mutations and CLDN18-ARHGAP fusions, which are thought to be specific to diffuse-type gastric cancers.

Gastric hepatoid adenocarcinomas are a genetically heterogenous group; most tumors show chromosomal instability, but MSI tumors do exist

The Cancer Genome Atlas Research Network classified gastric adenocarcinoma into four molecular subtypes: (1) Epstein-Barr virus-positive (EBV), (2) microsatellite-instable (MSI), (3) chromosomal instable (CIN), and (4) genomically stable (GS). The molecular subtypes of gastric hepatoid adenocarcinomas are still largely unknown. We analyzed 52 hepatoid adenocarcinomas for the expression of surrogate markers of molecular subtypes (MLH1, p53, and EBER in situ hybridization) and some biomarkers (p21, p16, Rb, cyclin D1, cyclin E, β-catenin, Bcl-2, IMP3, ARID1A and HER2), and mutations of TP53, CTNNB1, KRAS, and BRAF. We analyzed 36 solid-type poorly differentiated adenocarcinomas as a control group. Hepatoid adenocarcinomas were categorized as follows: EBV group (EBER-positive), no cases (0%); MSI group (MLH1 loss), three cases (6%); "CIN or GS" (CIN/GS) group (EBER-negative, MLH1 retained), 49 cases (94%). In the CIN/GS group, most of the tumors (59%) had either p53 overexpression or TP53 mutation and a coexisting tubular intestinal-type adenocarcinoma component (90%), suggesting that most hepatoid adenocarcinomas should be categorized as a true CIN group. Hepatoid adenocarcinomas showed relatively frequent expressions of HER2 (score 3+/2+: 21%/19%). Hepatoid adenocarcinomas showed shorter survival, more frequent overexpressions of p16 (67%) and IMP3 (98%) than the control group. None of hepatoid adenocarcinomas had KRAS or CTNNB1 mutations except for one case each, and no hepatoid adenocarcinomas had BRAF mutation. In conclusion, gastric hepatoid adenocarcinomas are a genetically heterogenous group. Most hepatoid adenocarcinomas are "CIN," but a small number of hepatoid adenocarcinomas with MSI do exist. Hepatoid adenocarcinomas are characterized by overexpressions of p16 and IMP3.

Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas.

OTX homeobox (HB) genes are expressed during embryonic morphogenesis and during the development of olfactory epithelium in adult organisms. Mutations occurring in these genes are often related to tumorigenesis in human. No data are available today regarding the possible correlation between OTX genes and tumors of the nasal cavity. The aim of this work is to understand if OTX1 and OTX2 can be considered as molecular markers in the development of nasal tumors. We selected nasal and sinonasal adenocarcinomas to investigate the expression of OTX1 and OTX2 genes through immunohistochemical and real-time PCR analyses.Both OTX1 and OTX2 were absent in all the samples of sinonasal Intestinal-Type Adenocarcinomas (ITACs). OTX1 mRNA was identified only in Non-Intestinal Type Adenocarcinomas (NITACs) while OTX2 mRNA was expressed only in Olfactory Neuroblastomas (ONs). We have demonstrated that the differential gene expression for both OTX1 and OTX2 genes might be a useful molecular marker to distinguish the different types of sinonasal tumors.

Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas

OTX homeobox (HB) genes are expressed during embryonic morphogenesis and during the development of olfactory epithelium in adult organisms. Mutations occurring in these genes are often related to tumorigenesis in human. No data are available today regarding the possible correlation between OTX genes and tumors of the nasal cavity. The aim of this work is to understand if OTX1 and OTX2 can be considered as molecular markers in the development of nasal tumors. We selected nasal and sinonasal adenocarcinomas to investigate the expression of OTX1 and OTX2 genes through immunohistochemical and real-time PCR analyses.Both OTX1 and OTX2 were absent in all the samples of sinonasal Intestinal-Type Adenocarcinomas (ITACs). OTX1 mRNA was identified only in Non-Intestinal Type Adenocarcinomas (NITACs) while OTX2 mRNA was expressed only in Olfactory Neuroblastomas (ONs). We have demonstrated that the differential gene expression for both OTX1 and OTX2 genes might be a useful molecular marker to distinguish the different types of sinonasal tumors.

Clinicopathological characteristics of patients with mucinous adenocarcinoma of the uterine cervix: A retrospective study of 21 cases

ObjectivesFew studies in the literature take into account the WHO’s 2014 redefinition of the characteristics of mucinous adenocarcinoma of the uterine cervix. Our objective was to describe the characteristics of a group of these patients. Material and methodsThis was a retrospective descriptive study of patients diagnosed between 1 January 2005 and 31 May 2016 in three hospitals in Lyon, France. All the cases of cervical adenocarcinoma were reanalysed by an expert in gynaecological pathology to retain the mucinous subtypes as defined in the 2014 WHO classification. We analysed their clinical and pathological characteristics. ResultsAmong the 82 cases of cervical adenocarcinoma, 21 (26%) were diagnosed as mucinous. Ten were gastric type, of which four were in the extremely well differentiated form of minimal deviation adenocarcinomas, six were intestinal type, two were signet-ring cell type, and three were not otherwise specified. The patients’ mean age was 42 years and 18 patients were premenopausal. The revealing symptom was metrorrhagia in eight cases (38%) and mucinous vaginal discharge in four (19%). Fifteen (72%) of the cervical smear were abnormal. Five (31%) of the 16 patients with gastric or intestinal type adenocarcinoma had a specific radiological presentation: multiple cysts of the uterine isthmus, visible on ultrasound and with T2 hyperintensity on MRI. ConclusionMucinous adenocarcinoma is a rare form of cervical cancer that can be confused with other pathological types. It can be detected using cervical smears and should be suspected in cases of mucinous discharge and characteristic MRI features.

Update on the Diagnosis and Management of Gastric Intestinal Metaplasia in the USA.

Gastric intestinal metaplasia (GIM) is a premalignant condition that can lead to intestinal-type gastric adenocarcinoma. It is characterized by a change in the gastric mucosa to a small-intestinal phenotype. Infection with Helicobacter pylori is the most common factor associated with GIM. Although GIM is typically a histologic diagnosis, various techniques have been developed to enable the endoscopic identification of GIM. There are presently no widely accepted guidelines on screening and surveillance strategies in patients with GIM in the USA. The aim of this review is to provide an update regarding the problem, diagnosis, and management of GIM in the USA.

Tumor Budding and Prognosis in Gastric Adenocarcinoma.

Tumor budding has been associated with poor prognosis in several cancer types, but its significance in gastric cancer is unknown. The aim of this study was to assess the prognostic significance of tumor budding in gastric adenocarcinoma, and its main histologic types. Some 583 gastric adenocarcinoma patients who underwent surgery in Oulu University Hospital during the years 1983-2016 were included in this retrospective cohort study. Tumor budding was counted per 0.785 mm fields from the slides originally used for diagnostic purposes. Patients were divided into low-budding (<10 buds) and high-budding (≥10 buds) groups. Tumor budding was analyzed in relation to 5-year survival and overall survival. Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for confounders. Determining tumor budding was difficult in diffuse-type cancer due to the uncohesive growth pattern of these tumors. Patients with high tumor budding had worse 5-year survival compared with patients with low tumor budding (adjusted HR, 1.55; 95% CI, 1.20-2.01). In intestinal-type adenocarcinomas, the high-budding group had significantly poorer 5-year survival compared with the low-budding group (adjusted HR, 1.57; 95% CI, 1.14-2.15). There were no differences in 5-year survival between the budding groups in the diffuse type adenocarcinoma. In conclusion, high tumor budding is an independent prognostic factor in gastric adenocarcinoma, but its value is limited to the intestinal type of gastric adenocarcinoma. In diffuse type gastric adenocarcinoma, the assessment of tumor budding is hardly feasible, and it does not have prognostic relevance.

A BAP31 intrabody induces gastric cancer cell death by inhibiting p27kip1 proteasome degradation.

B-cell receptor-associated protein 31 (BAP31) is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein that has been found to be overexpressed in gastric intestinal-type adenocarcinoma. We first studied the relationship of BAP31 with 84 kinds of tumor-associated antigens and found that BAP31 can specifically interact with and regulate the proteasome degradation of the cyclin kinase inhibitor p27kip1 , which is one of the most frequently dysregulated tumor suppressor proteins in human cancers. Therefore, we screened antibodies against BAP31 from a human VH single-domain antibody library and expressed the antibodies intracellularly. It was found that one of the intrabodies (VH-D1) specifically inhibited p27kip1 proteasome degradation, possibly by blocking the combination of BAP31 with p27kip1 . VH-D1 displayed therapeutic effects, as it was able to reduce the growth of human gastric cancer (GC) cell xenografts in nude mice. This effect was due to inhibition of the proliferation and subsequent activation of caspase-dependent apoptosis. Thus, BAP31 is a potential target for the suppression of GC via an intrabody-based approach.

Transnasal endoscopic surgery in selected nasal-ethmoidal cancer with suspected brain invasion: Indications, technique, and outcomes.

In nasal-ethmoidal malignancies, brain involvement is associated with dismal prognosis. Patients undergoing endoscopic resection with transnasal craniectomy and subpial dissection (ERTC-SD) for brain-invading nasal-ethmoidal cancer between 2008 and 2016 were included. Complications were analyzed in all patients, whereas oncological outcomes only in patients with pathological brain invasion. The prognostic impact of previous treatments, brain edema, and histology was assessed. Hospitalization ratio was calculated. Nineteen patients received ERTC-SD and 11 had pathological-proven brain invasion. Histologies were 6 olfactory neuroblastomas (ONB), 3 neuroendocrine carcinomas, and 2 intestinal-type adenocarcinomas. Mean follow-up was 21.9 months. Three-year overall, local recurrence-free, and distance recurrence-free survivals were 65.5%, 81.8%, and 68.2%, respectively. Overall and distant recurrence-free survivals were significantly better in patients with ONB (P = 0.032 and P = 0.013, respectively). Hospitalization ratio was 4.1%. Complication rate was 10.5%. In selected nasal-ethmoidal tumors with brain invasion, ERTC-SD can provide good local control, satisfactory survival, and limited morbidity.

National distribution of stomach cancer incidence in Iran: A population-based study

Backgrounds and Aims: Stomach cancer (SC) is the fourth most common cancer and the second leading cause of death due to cancer in the world. The aim of this study was to investigate the provincial distribution as well as age-specific incidence of SC in both genders across Iran. Materials and Methods: This ecological study was conducted according to re-analysis of medical records aggregated to provinces from National Registry of Cancer and Disease Control and Prevention report of the Ministry of Health and Medical Education for SC in 2008. For each province, the average annual age-standardised rate (ASR) for the incidence of SC was calculated. Results: Our findings showed that in Iran, adenocarcinoma, not otherwise specified, was the most common histological type of SC in both genders (59% in males and 56% in females), while intestinal type of adenocarcinoma had the lowest prevalence (14% in males and 12% in females). In age groups above 45 years, there was a steady upward trend, and the highest ASR in both genders was related to 80–84 years of age with 292.14 and 112/100,000 in males and females, respectively. Conclusion: The assessment of geographical distribution showed that there is a wide geographical variation in the incidence of SC across the 31 provinces of Iran, and the ASR of SC in South-East and North-West parts of Iran was higher than any other areas. Thus, development access to screening services and carryout of prevention programs should be considered for high-risk groups in these areas.

Sinonasal nonsalivary-type adenocarcinoma: A 9-year experience from a tertiary cancer center in South India

Background: Sinonasal tract malignancies are uncommon, representing not more than 5% of all head and neck neoplasm. Primary non-salivary type adenocarcinomas of the sinonasal tract are rare and may originate from respiratory surface epithelium or the underlying seromucinous glands. They are classified into intestinal type adenocarcinoma (ITAC) and non-intestinal type adenocarcinoma (non-ITAC) based on immunophenotypic features. Materials and Methods: We retrieved five cases of ITACs and twelve cases of non-ITACs from our archives over a period from 2010-2018. Results: All cases of ITACs occurred in the nasal cavity. There was a male predilection with ratio of 4:1, mean age being 48 years. Two cases had association with occupational risk factors. All cases showed positivity for CK20. Non-ITACs occurred in older age group with mean age of 52 years. Male to female ratio was 2:1. Apart from nasal cavity, ethmoid, maxillary, frontal and sphenoid sinuses were involved. Though occupational risk factors have not been established for non-ITAC, five of our cases gave history of exposure to risk factors. Non-ITACs showed positivity for CK7 and were negative for CK20. Conclusion: Surgery is the first line of management followed by adjuvant radiotherapy. Three cases of non-ITACs developed recurrence while on follow up. Recurrence in one case was after five years of initial diagnosis. Follow-ups over long period of time are required. Multiinstitutional studies are needed for better understanding these rare cancers.

Synchronous adenocarcinoma and gastrointestinal stromal tumor in the stomach - report of two cases

Introduction. Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor that occurs in the gastrointestinal tract, most commonly in the stomach or the small intestine. The surgery of the stomach is the dominant way of treatment of these tumors. The synchronous detection of adenocarcinoma and gastric GIST is not a very common condition, which is often diagnosed intraoperatively and has a significant impact on the prognosis of these patients. Outline of cases. We herein report two cases of gastric GIST with synchronous adenocarcinoma tumors, which were detected incidentally, intraoperatively, while the patients were undergoing surgery for a primary gastric adenocarcinoma. The first case was of a 76-year-old female patient. The histopathological analysis of the operative specimen firstly showed a poorly differentiated advanced gastric adenocarcinoma. The second tumor, from the gastric serosa, was a spindle cell GIST of low risk. It was diffusely positive for DOG1, CD34, and CD117. Its proliferative index was established using the Ki67 antibody. The number of mitoses was one per 5 mm2. The second case was of a 65-year-old male patient. The histopathological analysis revealed an early, well-differentiated, intestinal type adenocarcinoma of the gastric mucosa. The synchronous tumor from the serosa of the stomach was a spindle cell gastrointestinal stromal tumor (CD34, DOG1, and CD117 diffusely positive) of low risk. The proliferative index of this tumor, labeled with the Ki67 antibody, was very low. Necrosis was not present, nor was mitosis. Conclusion. Synchronous adenocarcinomas and GIST of the stomach are not very commonly associated, and are usually detected intraoperatively and after an immunohistochemical analysis. Recognition of this condition has a very important role in a differential diagnosis and the exclusion of metastases of malignant tumor deposits. Based on the tumor severity, the radicalness of the surgical intervention is determined, which affects the outcome of these patients.

Metastatic rectal adenocarcinoma in the maxillary bone: A case report

Introduction: Colorectal cancer patients presenting with isolated bone metastases are exceedingly rare. Case Report: A 72-year-old male patient appeared with a painless gross swelling in the anterior maxillary gingiva, nearly a year after anterior rectal resection for cancer. The patient was submitted to lesion excision and nasolabial flap reconstruction. Histology revealed an intestinal type adenocarcinoma. The patient underwent radiotherapy. The disease spread and our patient lost his battle with cancer. Conclusion: Rectal tumor metastasis to maxillary bone is exceedingly rare and a high index of suspicion must be maintained in order to timely diagnose and treat it. Intraoral reconstruction with a nasolabial flap is a simple and fast procedure with good cosmetic and functional results.

Role of H pylori in GERD- A prospective study

Introduction: The role of Helicobacter pylori in esophageal disease has not been clearly defined. To clarify this issue, we analyzed 120 patients with histologically confirmed esophageal disease. Helicobacter pylori (H. pylori) causes a long-term infection of the human gastric and duodenal mucosa (1). Mucosal colonisation predisposes for peptic ulcer disease, atrophic gastritis and distal (antral) stomach cancer (2), with various effects on gastric acid secretion. Genetic variability of H. pylori is high (3). Several genes have been identified that may play a role in the pathogenicity (4, 5). Most important is the cytotoxin- associated gene A (CagA), which is associated with peptic ulcer disease (6), and intestinal type adenocarcinoma of the stomach (7). Patients with duodenal ulcer often have high basal gastrin levels, high peak acid output and high 24-hour intragastric acidity (8-10). Materials and methods: This investigation was performed at the RL Jalappa Hospital, Tamaka, Kolar in patients who underwent Upper GI Endoscopy. The time of investigation was from January 2016-December 2018. Results: This study included 30 patients with BE out of 120 patients with GERD. The average age of patients in BE group was 52.4 years. (SD } 10.8 yr.) In the GERD group average age was 40.8 years. In all groups included in this study, men were more represented than women. In BE group, H. pylori infection was present in 16.0% of patients. In GERD group, H. pylori infection was present in 42.9%. Conclusion: The prevalence of H. pylori infection in patients with BE was lower in comparison with patients with GERD (p