Intestinal-type Adenocarcinoma Research Articles

Potential value of CT radiomics in the distinction of intestinal-type gastric adenocarcinomas.

The purpose of the study was to investigate the role of CT radiomics for the preoperative distinction of intestinal-type gastric adenocarcinomas. A total of 187 consecutive patients with preoperative contrast CT examination and pathologically proven gastric adenocarcinoma were retrospectively collected. Patients were divided into a training set (n = 150) and a test set (n = 37). Arterial phase (AP), portal phase (PP), and delay phase (DP) images were retrieved for analysis. A dedicated postprocessing software was used to segment the lesions and extract radiomics features. Random forest (RF) algorithm was applied to construct the classifier models. A nomogram was developed by incorporating multiphase radiomics scores. Receiver operating characteristic (ROC) curves were used to evaluate the performance of the radiomics model and nomogram in both sets. The radiomics model showed a favorable capability in the distinction of intestinal-type gastric adenocarcinomas. The areas under curves (AUCs) of the AP, PP, and DP radiomics models were 0.754 (95% CI: 0.676, 0.820), 0.815 (95% CI: 0.744, 0.874), and 0.764 (95% CI: 0.688, 0.829) in the training set, respectively, which were confirmed in the test set with AUCs of 0.742 (95% CI: 0.572, 0.872), 0.775 (95% CI: 0.608, 0.895), and 0.857 (95% CI: 0.703, 0.950), respectively. The nomogram yielded excellent performance for distinguishing intestinal-type adenocarcinomas in both sets, with AUCs of 0.928 (95%: 0.875, 0.964) and 0.904 (95% CI: 0.761, 0.976). The multiphase CT radiomics nomogram holds promise for the individual preoperative discrimination of intestinal-type gastric adenocarcinoma. • CT radiomics has a potential role in the distinction of intestinal-type gastric adenocarcinomas. • Single-phase enhanced CT-based radiomics showed favorable capability in distinguishing intestinal-type tumors. • The nomogram which incorporates the multiphase radiomics scores could facilitate the individual prediction of intestinal-type lesions.

Helicobacter pylori Infection Facilitates the Expression of Resistin-like Molecule Beta in Gastric Carcinoma and Precursor Lesions

Helicobacter pylori (H. pylori) was reported to be associated with gastric carcinogenesis. Resistin-like molecule beta (RELMβ), a recently described goblet cell-specific protein, was demonstrated to aberrantly express in gastric cancer and correlated with its clinicopathological features. This study aimed to examine the association between H. pylori and RELMβ expression in gastric carcinoma and precursor lesions. H. pylori infection and RELMβ expression were immunohistochemically evaluated in gastric biopsies from 230 patients. The biopsies consisted of normal gastric mucosa (n=20), mucosa with chronic gastritis (n=41), intestinal metaplasia (n=42), dysplasia (n=31), intestinal-type adenocarcinoma (n=56), and diffuse-type adenocarcinoma (n=40). RELMβ expression was measured in gastric biopsies after H. pylori eradication therapy in a subgroup of 32 patients. Cultured gastric cancer cell line SGC-7901 was infected with H. pylori strains, and RELMβ expression was detected by reverse transcription PCR, real-time PCR and Western blotting. Higher RELMβ immunoreactivity was observed in H. pylori-positive intestinal metaplasia (P=0.003), dysplasia (P=0.032), intestinal-type (P=0.037) and diffuse-type adenocarcinomas (P=0.001) than in H. pylori-negative specimens. Expression rates of RELMβ in dysplasia (P=0.005), intestinal-type adenocarcinoma (P<0.001), and diffuse-type adenocarcinoma (P=0.001) were significantly correlated with the grade of H. pylori density. In addition, H. pylori eradication reduced the RELMβ intensity in intestinal metaplasia (P=0.001). Infection of gastric cancer SGC-7901 cells with cag pathogenicity island (PAI)-positive H. pylori TN2, but not with its PAI totally deleted mutant (TN2-ΔPAI) for 4-8 h, resulted in enhanced protein and transcript levels of RELMβ (P<0.05). In summary, our study suggested that H. pylori infection facilitated the expression of RELMβ in gastric garcinoma and precursor lesions.

Tumor budding is an adverse prognostic marker in intestinal-type sinonasal adenocarcinoma and seems to be unrelated to epithelial-mesenchymal transition.

Intestinal-type adenocarcinoma (ITAC) of sinonasal tract is a rare malignant tumor with strong morphological, immunophenotypical, and molecular similarities to colorectal adenocarcinoma (CRC). Tumor budding (TB) is a well-established adverse prognostic marker in CRC and some head and neck tumors, with features of epithelial-mesenchymal transition (EMT). The aim of this study was to assess TB in ITAC and to evaluate its possible association with EMT markers in this setting. We selected 32 surgically resected specimens of non-mucinous/non-signet ring ITAC and evaluated them for TB according to the international recommendations developed for CRC. The expression of the EMT markers E-cadherin, ZEB1, ZEB2, SLUG, and SNAIL was evaluated by immunohistochemistry (IHC). Results were stratified using clinical and follow-up data (2/32 patients had metastatic disease and 4/32 died of disease). We observed TB in 13/32 (40.6%) ITAC cases including the 7 patients with relapse (p = 0.0005) and the 4 patients dead of disease (p = 0.02). Lymphovascular invasion was associated with TB (p = 0.008). Absence of TB was associated with low ZEB2 expression (p = 0.003). No other association with EMT markers emerged. Occupational exposure to wood and leather dust was not related to the presence of TB. TB interobserver concordance was substantial (proportion of agreement = 87%; Cohen's kappa = 0.73). This work suggests that TB is associated with a worse prognosis in ITAC, but our findings do not seem to support the involvement of EMT in this specific setting. Further larger studies are needed to address this point.

Distinct expression and prognostic values of the replication protein A family in gastric cancer.

The replication protein A (RPA)1-4 family are single-stranded DNA-binding proteins that are essential components of DNA replication, repair and recombination, and cell cycle regulation. The present study aimed to evaluate the prognostic value of the RPA family members in patients with gastric cancer (GC), using datasets retrieved from the Oncomine public database. Datasets were retrieved for the purpose of comparing the RPA expression levels between GC and normal tissues. Additionally, Kaplan-Meier analysis was used to compare the overall survival (OS) times of GC patients that expressed different levels of RPA proteins. RPA1, 2, and 3 expression levels were all significantly upregulated in gastric intestinal-type, diffuse gastric, and gastric mixed adenocarcinomas, compared with those in normal mucosal tissues. Moreover, high mRNA expression levels of RPA3 and 4 predicted poorer OS times in all GCs, as well as patients with human epidermal growth factor receptor 2-negative and -positive GC. The high-risk group, separated by RPA signature, showed a poorer outcome than the low-risk group. RPA3 was the most strongly correlated with CD4+ T-cell levels. In conclusion, RPAs are novel prognostic indicators in GC, and can also predict the features of immunological diseases. Future experimental investigation into the roles of RPAs concerning the pathogenesis and development of GC may provide a novel biomarker or therapeutic target, improving the prognosis of patients with GC.

Management of sinonasal adenocarcinomas with anterior skull base extension.

Sinonasal adenocarcinomas (SNAC) are rare and heterogeneous. Management of SNAC follows a rather standardized and internationally accepted paradigm. Several refinements have been introduced during the last decade. A narrative review of most updated literature on SNACs has been conducted. SNACs are classified as intestinal-type and non-intestinal-type, which are further categorized according to grade. Preoperative work-up should include magnetic resonance imaging (or contrast-enhanced computed tomography as a secondary or complementary choice) and biopsy under general anesthesia, or under local anesthesia in case of a history of exposure to wood and/or leather dust. Positron emission tomography, neck ultrasound, and fine-needle aspiration cytology are indicated in selected cases. Surgery represents the most common upfront modality of treatment and is usually accomplished via a transnasal endoscopic approach. Adjuvant radiation therapy is indicated for high-grade, locally advanced tumors and/or in case of margins involvement. Neoadjuvant chemotherapy with cisplatin, 5-fluorouracil and leucovorin may offer high response rates and long-term control in a subgroup of patients affected by intestinal-type adenocarcinoma, and in particular in those whose tumors harbor a functional p53 protein. Most of the bio- and immune-therapeutic potentials on SNACs still remain theoretical, and no clinical data are currently available. Management of SNAC consists of histological diagnosis, radiological staging, radical surgery, and adjuvant radiation therapy. Neoadjuvant chemotherapy can be indicated in selected cases. The role of biotherapy and immune therapy still needs to be elucidated.

Immunohistochemical analysis of beta-catenin, E-cadherin and p53 in canine gastrointestinal epithelial tumors.

Wnt/beta-catenin signaling, E-cadherin and p53 reportedly play important roles in the development and/or progression of human gastrointestinal cancer. The present study evaluated the roles of beta-catenin, E-cadherin and p53 in canine gastrointestinal tumors. Endoscopic biopsy or surgically resected samples, a total of 131, including 38 gastric, 13 small intestinal and 80 large intestinal tumors, were obtained from 95 dogs. Those specimens were examined pathologically. Immunohistochemically, nuclear beta-catenin expression was found in 88% (42/48) of polypoid type adenocarcinomas. Most cases of non-polypoid type adenocarcinomas lacked nuclear expression of beta-catenin with the exception of one case (6%, 1/17). Nuclear beta-catenin expression was not observed in signet ring cell carcinomas (0/15), mucinous adenocarcinomas (0/7) and undifferentiated carcinomas (0/4). The findings indicate that nuclear translocation of beta-catenin is closely related to the development of polypoid type adenocarcinomas but not that of non-polypoid type malignant tumors. The immunoreactivity of E-cadherin for tumor cells tended to decline overall in most of cases including benign tumors. Significant immunoreactivity for p53 was not found in 61% of tumors examined (80/131), including malignant tumors (63%, 57/91), while intense p53-immunoreactivity was rarely found in a few cases of malignant tumors (8%, 7/91). We could not conclude clearly significant correlations between histopathological tumor types and immunohistochemical results of E-cadherin or p53. This paper indicates the importance of the nuclear translocation of beta-catenin for the tumorigenesis of canine intestinal polypoid type adenocarcinomas, especially in the colorectum.

The Evolving Role of Systemic Therapy in the Primary Treatment of Sinonasal Cancer.

The inclusion of systemic therapy in the multimodal approach of locally advanced sinonasal cancers, at least in some selected histologies, may improve locoregional control and reduce the frequency of distant metastasis, allowing longer survival. Response to induction chemotherapy is a strong prognostic factor for a patient's outcome and it may improve disease control by surgery and radiation. Concurrent chemoradiation aims at increasing locoregional control in squamous cell cancer of the head and neck; this is particularly important in sinonasal cancers, with a risk of local relapse of about 30%. Selected histologies may benefit from specific drug combinations, according to varying chemosensitivity. Intestinal-type adenocarcinoma carrying a functional p53 protein may be treated with preoperative cisplatin, 5-fluorouracil, and leucovorin. Sinonasal undifferentiated carcinoma is a chemosensitive disease, where the multimodal approach is necessary to counterbalance the severe prognosis. Sinonasal neuroendocrine carcinoma and olfactory neuroblastoma may benefit from systemic treatments, but their added value has not been so clearly defined yet. Multimodality trials are ongoing to test the activity of induction chemotherapy followed by locoregional curative treatment. A deeper knowledge of the molecular deregulations of these diseases could help in identifying targeted therapies.

Intestinal-type histology is associated with better prognosis in patients undergoing liver resection for gastric/esophagogastric-junction liver metastasis.

The indication for resection of gastric/esophagogastric-junction liver metastasis (GELM) has yet to be established. This study aimed to investigate prognostic factors in patients undergoing GELM resection. From 2001 to 2015, 31 consecutive patients underwent resection for GELM; and factors for poor prognosis were evaluated. Of the 31 patients, 23 (74.2%) developed multiple liver metastases. The histology of gastric cancer was intestinal-type adenocarcinoma in 21 patients (67.7%). Median overall survival (OS) was 3.2 years. The 1-, 3-, and 5-year OS rates were 92.8%, 56.2%, and 42.2%, respectively. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 58.5%, 31.3%, and 31.3%, respectively. Multivariate analysis indicated that intestinal-type adenocarcinoma was associated with a significantly lower risk of OS (hazard ratio [HR], 0.26; p =0.022) and RFS (HR, 0.25; p = 0.008). In multiple logistic regression analysis, intestinal-type adenocarcinoma (odds ratio, 0.14; p = 0.012) reduced incidence of extra-hepatic recurrence after GELM resection. In conclusion, GELM resection in patients with intestinal-type histology is preferable because intestinal-type adenocarcinoma is associated with better prognosis and a lower incidence of extra-hepatic recurrence than diffuse/other-type adenocarcinoma.

IDH2 Mutation Analysis in Undifferentiated and Poorly Differentiated Sinonasal Carcinomas for Diagnosis and Clinical Management.

A large number of tumor types arise from the mucosa of the sinonasal cavities. Although presenting clinically distinct behavior, due to poorly differentiated histologic features, they can be difficult to classify correctly. Our aim was to investigate whether IDH2 and IDH1 mutations may be specific to a subset of undifferentiated and poorly differentiated sinonasal carcinomas. A total of 125 tumor samples of 7 different histologic subtypes were analyzed for IDH mutations by sequencing and mutant-specific immunohistochemistry, and the results were correlated to clinical and follow-up data. The highest incidence of IDH2 mutations occurred in sinonasal undifferentiated carcinoma, with 11/36 (31%) cases affected. However, also, 1/9 neuroendocrine carcinomas, 2/4 high-grade non-intestinal-type adenocarcinomas, and 1/8 poorly differentiated squamous cell carcinomas carried the IDH2 mutation, whereas 1/48 intestinal-type adenocarcinomas harbored an IDH1 mutation. Immunohistochemical analysis of mutant IDH1/2 produced a number of false-negative results, but also 1 false-positive tumor was found. Disease-specific survival was more favorable in IDH2-mutant versus wild-type cases. Our data suggest that IDH-mutant sinonasal cancers, independent of their histologic subtype, may represent a distinct tumor entity with less aggressive clinical behavior. Clinically, patients with these mutations may benefit from specific IDH-guided therapies.

From This Month's Histopathology

Despite good evidence that screening for Lynch Syndrome (LS) in endometrial carcinoma (EC) cases has high potential for reducing morbidity, mortality, and healthcare costs, and the wide availability of screening tests, there remains huge variation in the approach to screening. Pathologists need to be aware of the implications of LS screening for the patient and her family. Standardised and external quality-assured protocols should be developed and adopted for LS screening in EC cases. The International Society of Gynaecological pathology (ISGyP) has recently recommended that all newly diagnosed EC cases undergo testing for LS…We also suggest that all newly diagnosed patients with ovarian endometrioid or clear cell carcinoma are similarly screened for LS. MSH2 loss in a case of known germline MSH2 mutation. study Ryan et al. (p. 814) In conclusion, SDHB immunohistochemistry can be a useful tool for the differential diagnosis of pulmonary chondromas and hamartomas, in cases when this distinction is difficult based on histological features alone. Loss of SDHB expression in pulmonary chondromas may also assist in the identification of patients who may have Carney triad and are therefore at risk of developing more aggressive neoplasms. Succinate dehydrogenase B (SDHB) immunohistochemical staining in a case of chondroma. Cartilaginous cells (left) are not reactive. Endothelial cells (right) show granular cytoplasmic reactivity: SDHB expression is lost. Chatzopoulos et al. (p. 826) In summary, we have shown that a Ki67 PI of ≥25 was associated with poorer survival in high-grade Olfactory Neuroblastomas (ONBs), and that high-grade ONBs show more intratumoral Tumour Infiltrating Lymphocytes (TILs) than low-grade ONBs…and the CD4/CD8 ratio could also represent an interesting prognostic marker. This series confirms the importance of histological grading, and that a careful evaluation of TILs could prove to be a powerful prognostic tool for identifying patients with distinct clinical behaviours and responses to immunotherapeutic strategies. Ki67 proliferation index (PI) in a Hyams Grade I olfactory neuroblastoma. Classe et al. (p. 854) In summary, this study investigated the largest cohort, to our knowledge, of Nested Variant urothelial Carcinoma (UVUC) to date and aimed to identify the mutational and molecular backgroundsof this rare UC variant. NVUC seems to be characterised by a high frequency of TERT mutations and low frequency of mutations in FGFR3 and the mTOR, MAPK and PIK3 pathways. Mutations of Wnt and inflammatory pathways, including JAK3 mutations, may indicate a differential mutational landscape of this specific histomorphological variant compared to conventional UBC. Moreover, we were able to assign NVUC to the luminal subtype of UC. Our findings may be of significance in understanding the pathogenesis of this rare variant and may guide further diagnostic, prognostic and therapeutic applications. Heatmap presenting immunohistochemistry results for luminal and basal markers in NVUC. Weyerer et al. (p. 866) In conclusion, the analysis of stromal maturity in gastric cancer is feasible with moderate reproducibility, and stromal maturity is an independent prognostic factor in gastric adenocarcinoma… classification of stromal response in this tumour type would benefit from more detailed criteria, preferably based on those biological mechanisms of the response mediating the prognostic effect.. Studies in neoadjuvant-treated patients and early-stage gastric cancer are warranted. 5-year overall survival of patients with intestinal-type gastric adenocarcinoma. Kemi et al. (p. 883) We have shown that Vacuum-assisted large-core biopsy (VALCB) is reliable for excluding malignancy, and allows the avoidance of surgical excision when there is no discordance between radiological and histological findings, and no associated atypia on biopsy. When a VALCB contains atypia, additional risk factors are the non-incidental finding of the RS/CSL, the mammographic appearance, and the number of fragments sampled being <12. When they are present, surgery remains safer. Example of a benign biopsy with a pure radial scar/complex sclerosing lesion. Bacci et al. (p. 901)

Apparent diffusion coefficient-based histogram analysis differentiates histological subtypes of periampullary adenocarcinoma.

BACKGROUNDFor periampullary adenocarcinoma, the histological subtype is a better prognostic predictor than the site of tumor origin. Intestinal-type periampullary adenocarcinoma (IPAC) is reported to have a better prognosis than the pan-creatobiliary-type periampullary adenocarcinoma (PPAC). However, the classification of histological subtypes is difficult to determine before surgery. Apparent diffusion coefficient (ADC) histogram analysis is a noninvasive, non-enhanced method with high reproducibility that could help differentiate the two subtypes.AIMTo investigate whether volumetric ADC histogram analysis is helpful for distinguishing IPAC from PPAC.METHODSBetween January 2015 and October 2018, 476 consecutive patients who were suspected of having a periampullary tumor and underwent magnetic resonance imaging (MRI) were reviewed in this retrospective study. Only patients who underwent MRI at 3.0 T with different diffusion-weighted images (b-values = 800 and 1000 s/mm2) and who were confirmed with a periampullary adenocarcinoma were further analyzed. Then, the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values and ADCmin, ADCmax, kurtosis, skewness, and entropy were obtained from the volumetric histogram analysis. Comparisons were made by an independent Student's t-test or Mann-Whitney U test. Multiple-class receiver operating characteristic curve analysis was performed to determine and compare the diagnostic value of each significant parameter.RESULTSIn total, 40 patients with histopathologically confirmed IPAC (n = 17) or PPAC (n = 23) were enrolled. The mean, 5th, 25th, 50th, 75th, 90th, and 95th percentiles and ADCmax derived from ADC1000 were significantly lower in the PPAC group than in the IPAC group (P < 0.05). However, values derived from ADC800 showed no significant difference between the two groups. The 75th percentile of ADC1000 values achieved the highest area under the curve (AUC) for differentiating IPAC from PPAC (AUC = 0.781; sensitivity, 91%; specificity, 59%; cut-off value, 1.50 × 10-3 mm2/s).CONCLUSIONVolumetric ADC histogram analysis at a b-value of 1000 s/mm2 might be helpful for differentiating the histological subtypes of periampullary adenocarcinoma before surgery.

The distribution of gastric malignancies in AL-Diwaniyah province-Iraq, a retrospective study

Gastric cancer is one of the most common malignancies affecting gastrointestinal tract. It a multifactorial illness, both genetic and environmental factors involving in etiology. A wide variation in the incidence of gastric cancer in different geographical regions. Endoscopy is the most sensitive and specific method for the diagnosis. The aims of this study is to describe the distribution rate of gastric cancer in AL-Diwaniyah province in Iraq in correlation with the patients age, sex and the histopathological types of gastric cancer. From about (4078) patients who underwent gastroscopy for different indications at AL-Diwaniyah gastroenterology and hepatology center in Iraq during the period between November 2015 and April 2019, (76) patients were founded to have gastric cancer by documented histopathological study of tissue biopsy. Gastric cancer distribution was about (1.8%). Males are affected more than females in a ratio of (1.37:1). Out of (76) total number of patients with gastric cancer ;(69) patients (90.79%) having gastric adenocarcinoma ( most common type) with male to female ratio of (1.46:1). (5) Patients (6.58%) having gastrointestinal stromal tumors (GIST) and (2) patients ( 2.63%) having lymphoma. In patients with adenocarcinoma,(12) patients (17.39%) were less than (40 years) of age, (31) patients (44.93%) were between (40-60 years) and (26) patients (37.68%) were older than (60 years). The intestinal-type adenocarcinoma was the most common histopathological type (63.77%), followed by diffuse type (30.43%), mixed (4.35%) and mucinous(1.45%). Gastric cancer incidence is increasing with advance age; it still a public health and challenging problem. Mass screening or surveillance programs is the best method for the detection and diagnosis of gastric cancer at an early stage.

1742 A Rare Case of Colorectal Cancer of the Neoesophagus

INTRODUCTION: In the case that follows, we present a case and literature review of oligometastatic intestinal adenocarcinoma originating in a colonic interposition repair of esophageal atresia. Uniquely, the pathology of the tumor was consistent with colonic mucosa which only a few such instances have been reported in literature. CASE DESCRIPTION/METHODS: A 58-year-old female with a past medical history of tetralogy of Fallot (repaired at age 14), esophageal atresia status post esophageal colonic interposition, esophageal and pyloric stenosis, neo-esophageal polyp (found 2 years prior with biopsy showing reactive epithelial atypia), and atrial fibrillation on Coumadin presented to the hospital complaining of fatigue and dyspnea of one week duration. Her family history was significant for colon cancer in her father. Initial lab workup revealed a hemoglobin of 5. She was transfused 3 units of packed red blood cells. Due to severe symptomatic anemia, an upper endoscopy and colonoscopy were performed revealing an ulcerated mass, approximately 50% in circumference in the lower third of the esophagus, as well as moderate pyloric stenosis that prevented passage of the endoscope. The esophageal masswas not amenable to endoscopic excision due to undulations of the cardiac beat, however biopsy demonstrated invasive, moderately differentiated, intestinal-type adenocarcinoma (Figure 1). Given these findings a PET/CT scan was obtained which revealed a 2cm mass in the distal aspect of the interposed colonic segment and a 1.7 × 1.2cm hypodense mass in the medial segment of the left hepatic lobe, consistent with metastasis. She was referred to Cardiothoracic Surgery for tumor resection and Oncology for neoadjuvent chemotherapy. DISCUSSION: Oligiometastatic colorectal cancer or the esophagus is an extremely rare medical condition. Our patient had an initial polyp removed in 2016, that was read as reactive epithelial atypia. More diligent surveillance was likely warranted for her case. This was shown by Lindahl et al in long-term endoscopic follow-ups in patients with this condition. Of the 12 patients observed in the study, a variety of colonic pathology was foundranging from dysplasia, colonic polyp, and aneuploid cells. Given these findings, albeit rare, with one case report citing less than 15 instances, special considerations should be made for close surveillance of these patients. Although no specific treatment guidelines exist for this anomaly, there has been documented success with a curative resection.

Minimally invasive endoscopic transcribriform resection of malignant lesions of the skull base

Introduction: Malignant tumours of the sinonasal region - including those with invasion of the skull base - necessitate surgical resection. The majority of the cases give an opportunity to perform the procedure via minimally invasive, endoscopic approach, without external, craniofacial surgery. Aim: To assess our clinical experience in treating anterior skull base malignancies, performing minimally invasive endoscopic transcribriform resection. Method: Between February 2015 and July 2017, four male and one female patient underwent minimally invasive, endoscopic skull base procedure. The mean age was 64.6 years (59-70, median: 66). Every surgery was performed via transnasal, endoscopic transcribriform approach. In two cases Kadish C esthesioneuroblastomas, while in one case a T3N0 sinonasal non-differentiated carcinoma, a T1N0 intestinal type adenocarcinoma and a T4N0 squamous cell carcinoma was the indication of surgery, respectively. Results: The mean follow-up time was 22.8 months, between 14 and 46 months. Intraoperative complications did not occur during the procedures. Regarding the postoperative period, liquorrhoea and pneumocephalus occurred in one case. Complications were solved with lumbar drainage. During follow-up, neither residual nor recurrent tumour was observed in our patients. Conclusion: Endoscopic transcribriform resection of the skull base malignancies is a safe and viable alternative to the traditional open approach. Orv Hetil. 2019; 160(40): 1584-1590.

Treatment Outcome of a Combined Dose-Escalated Treatment Regime With Helical TomoTherapy® and Active Raster-Scanning Carbon Ion Boost for Adenocarcinomas of the Head and Neck.

Introduction: Data regarding treatment and survival outcome of patients with adenocarcinoma of the head and neck are limited to case reports and case series. As a consequence of lacking evidence, treatment guidelines do not exist. We aimed to analyze the effect of a bimodal irradiation regime with intensity modulated radiotherapy (IMRT) and carbon ion boost on local control (LC) and survival in adenocarcinoma patients for a large patient collective.Materials and Methods: Patient records of eighty consecutive patients treated between 2009 and 2018 were analyzed retrospectively and Kaplan-Meier estimates for LC, overall survival (OS) and progression-free survival (PFS) were compared among patients with salivary gland adenocarcinoma (SGAC), salivary duct adenocarcinoma (SDAC), and intestinal-type adenocarcinoma (ITAC) according to the World Health Organization (WHO). Prognostic factors were identified using the log-rank test and cox-regression modeling. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE).Results: Median follow-up was 41 months. The 3-year and estimated 5-year Kaplan-Meier rates for all patients were 83 and 75% for LC, 74 and 50% for OS and 60 and 53% for PFS, respectively. While bimodal RT for ITAC resulted in a significantly decreased 3-year LC rate of 50 vs. 93% for each SGAC and SDAC (p < 0.01), no statistical significant survival differences could be identified across the three groups regarding OS (p = 0.08) and PFS (p = 0.063). 3-year OS was 88% for SGAC, 78% for SDAC and 67% for ITAC and 3-year PFS was 72% for SGAC, 53% for SDAC and 44% for ITAC, respectively. Nevertheless, in subgroup analysis, OS for ITAC was significantly worse compared to SGAC (p = 0.024). In multivariate analysis, bilateral tumor side (vs. unilateral) solely could be identified as independent negative prognostic factor for LC (p < 0.01). Treatment was well-tolerated with 21% acute (n = 17) and 25% (n = 20) late grade ≥3 toxicities.Conclusion: Radiotherapy including active raster-scanning carbon ion boost for relatively radio resistant adenocarcinomas of the head and neck resulted in favorable survival outcome for salivary gland and salivary duct adenocarcinomas with moderate toxicity. However, local control and prognosis for bilateral intestinal-type adenocarcinomas (ITAC) seem to remain low even after dose-escalation.

Treatment of Sinonasal Adenocarcinoma: A Population-Based Prospective Cohort Study.

Objectives Sinonasal adenocarcinoma (AC) is a potentially curable disease despite being an aggressive malignancy. Long-term survival can be achieved with early diagnosis and adequate multidisciplinary treatment. Our goal was to evaluate outcomes for patients with AC treated at our institution. Design In a population-based consecutive prospective cohort, we conducted an analysis of all patients treated for surface epithelial AC between 1995 and 2018. Results Twenty patients were included, and follow-up was 100%. The mean follow-up time was 89 months for the entire cohort (112 months for patients with no evidence of disease). Intestinal-type AC was found in 65%, whereas nonintestinal-type AC was found in 35% of all cases; 75% had stage T3/4 disease. Tumor grade was intermediate/high in 65%. Eighteen patients underwent treatment with curative intent (craniofacial resection [CFR] in 61%, transfacial approach in 39%, adjuvant radiotherapy in 89%), achieving negative margins in 56% of cases. Overall survival (OS) rates were 90, 68, and 54% after 2, 5, and 10 years of follow-up, respectively, and the corresponding disease-specific survival (DSS) rates were 90, 73, and 58%. Age over 60 years, tumor with a maxillary origin, and microscopic bone invasion were negative prognostic factors. Radical CFR was correlated with better OS and DSS. Conclusion The high probability of achieving radicality with CFR, the low complication rate, the acceptable toxicity of modern irradiation modalities, and the promising survival rates indicate that this strategy might be considered a safe and an effective option for treating patients with very advanced sinonasal AC.

Outcomes of endoscopic submucosal dissection for intestinal-type adenocarcinoma with anastomosing glands of the stomach.

Gastric intestinal-type adenocarcinoma with anastomosing glands (IAAG) is characterized by architectural abnormality with frequent anastomosing glands and low-grade cytologic atypia. Clinicopathologic features and long-term outcomes of endoscopic submucosal dissection (ESD) for IAAG remain unclear. This study included 2828 patients who underwent ESD for early gastric cancers (EGCs) (78 IAAGs [2.6%] and 2893 well-differentiated [WD] or moderately differentiated [MD] EGCs [97.4%]). Clinicopathologic features and short-term and long-term outcomes of ESD for IAAG were reviewed and compared with those for WD or MD EGCs. Gastric IAAGs were larger and more likely to be confined to the lamina propria than WD or MD EGCs. Histological heterogeneity, flat or depressed lesion and lateral resection margin (LRM) involvement were observed with significantly higher frequencies in IAAGs than in WD or MD EGCs. En bloc with R0 resection and curative resection rates of IAAGs were 79.5% and 73.1%, respectively, and both were significantly lower than those of WD or MD EGCs (93.8% and 82.9%). LRM involvement accounted for 57.1% of the non-curative resection cases in gastric IAAGs. Half of IAAGs with LRM involvement had a crawling pattern at tumor periphery. Among patients undergoing curative ESD for IAAG, no recurrences occurred during a median 52months of follow-up. No lymph node metastasis was found in any of IAAG patients undergoing additional surgery after ESD. Gastric IAAGs have distinct clinicopathologic features from WD or MD EGCs. Given the favorable long-term outcomes after curative resection, ESD can be indicated for early gastric IAAGs.

Comprehensive analysis of histone modification-associated genes on differential gene expression and prognosis in gastric cancer.

Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications. In the present study, a Bioinformatics analysis of the expression of histone modification-associated genes in GC and normal tissues was performed by using datasets from Oncomine, the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The clinical data of GC patients were downloaded from TCGA to determine the association between histone modification-associated gene expression and clinicopathological parameters or survival of GC. Finally, lysine acetyltransferase 2A (KAT2A), nuclear receptor coactivator 1 (NCOA1), SMYD family member 5 (SMYD5), protein arginine methyltransferase 1 (PRMT1) and PRDF1-RIZ (PR)/Su(var)3-9, enhancer-of-zeste and trithorax (SET) domain 16 (PRDM16) were screened; KAT2A, SMYD5 and PRMT1 were upregulated, while PRDM16 expression was downregulated in GC. Analysis of the GEO and Oncomine datasets revealed that NCOA1 was upregulated, which was contrary to the result obtained with the TCGA stomach adenocarcinoma dataset. Aberrant expression of KAT2A, NCOA1, SMYD5 and PRMT1 was more obvious in gastric intestinal-type adenocarcinoma; low NCOA1 expression was associated with better overall survival of GC patients [hazard ratio (HR)=0.690, 95% CI=0.570-0.840, P<0.001] and was an independent predictor for patients diagnosed with GC (HR=0.639, 95% CI=0.437-0.933, P=0.020). Correlation analysis and protein-protein interaction network analysis indicated a close association between ATAD2 and estrogen receptor 1 (ESR1), PRMT1, NCOA1 and KAT2A. In conclusion, differential expression of KAT2A, NCOA1, SMYD5, PRMT1 and PRDM16 was identified in GC vs. normal tissues, low NCOA1 expression was associated with poor survival of GC and ATAD2 may interact with ESR1 to regulate NCOA1 and PRMT1 in GC.

Factors associated with technical difficulty of endoscopic submucosal dissection for early gastric cancer that met the expanded indication criteria: post hoc analysis of a multi-institutional prospective confirmatory trial (JCOG0607)

There are few reports on the technical difficulty of gastric endoscopic submucosal dissection (ESD). The aim of this study was to investigate the factors associated with the technical difficulty of ESD for early gastric cancer (EGC) using the data from the multicenter non-randomized confirmatory trial of expanded indication criteria of ESD (JCOG0607). The major inclusion criteria were as follows: (1) histologically proven intestinal-type adenocarcinoma; (2) cT1aN0M0; (3) lesion without finding of ulcer (UL-negative) with > 2cm in size, or UL-positive with ≤ 3cm; (4) age 20-75years. The difficult case was defined as ESD taking ≥ 120min, piecemeal resection, and/or developing perforation during procedure. Between June 2007 and October 2010, 470 patients were enrolled from 29 institutions. Median procedure time was 79 (range 14-462) min, and it was ≥ 120min in 127 patients. Twelve patients developed perforation during ESD, and the procedure time was ≥ 120min in 9 of them. Therefore, 130 patients (27.7%) were identified as difficult cases. Multivariable analysis showed that UL-negative with > 5cm (vs. UL-negative with ≤ 3cm, odds ratio, 24.993; 95% CI 6.130-101.897, p < 0.0001) had the largest odds ratio and followed by UL-negative with 3-5cm upper or middle portion of stomach and age ≤ 60years were significantly associated with difficulty. UL-negative lesion with > 3cm, upper or middle portion of stomach and age ≤ 60years were independent factors associated with technical difficulty of ESD for EGC. Trial registered number was UMIN000000737.

Inverse association of Helicobacter pylori cagPAI genotypes with risk of cardia and non-cardia gastric adenocarcinoma.

Iran is a high‐risk country for cardia gastric adenocarcinoma (CGA) in Central Asia, with an incidence rate five times the average global rate, and shows a high infection rate for Helicobacter pylori (69%). The aim was to examine the associations of multiple H. pylori cagPAI genotypes (ie cagH, cagL, cagG, and orf17) with the risk of CGA, non‐CGA, and different histological types of GA in Iran. A large number of H. pylori strains (N = 336) were successfully cultured and genotyped. Histopathological evaluations were performed. The analysis showed an inverse association between the cagH+ genotype and the risk of CGA and intestinal‐type gastric adenocarcinoma (IGA) (adjusted ORs; 0.312 and 0.283, respectively), where the controls were nontumors. The orf17 + genotype decreased the risk of non‐CGA and diffuse‐type gastric adenocarcinoma (DGA)(adjusted ORs; 0.310 and 0.356, respectively). When the controls were those with nonatrophic gastritis, the cagG + genotype was negatively associated with the risk of CGA, non‐CGA, IGA, and DGA (adjusted ORs; 0.324, 0.366, 0.306, and 0.303, respectively). We did not find such a significant association for the cagL+ genotype in multiple logistic regression analysis. Combination of the vacA c2 and cagPAI genotypes further decreased the risk estimates for GAs. This study showed the reverse association of H. pylori cagPAI genotypes—cagH + and cagG +—with the risk of CGA in male patients aged ≥ 55 in Iran. Presence of the vacA c2 genotype in combination with cagPAI genotypes showed strong inverse associations with the risk of CGA and non‐CGA. These findings may reveal a coordinated relationship between the vacA c2 and cagPAI genotypes.