International consensus on the management of large (≥20 mm) colorectal laterally spreading tumors: World Endoscopy Organization Delphi study.

OBJECTIVES: There have been significant advances in the management of large (≥20 mm) laterally spreading tumors (LSTs) or nonpedunculated colorectal polyps; however, there is a lack of clear consensus on the management of these lesions with significant geographic variability especially between Eastern and Western paradigms. We aimed to provide an international consensus to better guide management and attempt to homogenize practices. METHODS: Two experts in interventional endoscopy spearheaded an evidence-based Delphi study on behalf of the World Endoscopy Organization Colorectal Cancer Screening Committee. A steering committee comprising six members devised 51 statements, and 43 experts from 18 countries on six continents participated in a three-round voting process. The Grading of Recommendations, Assessment, Development and Evaluations tool was used to assess evidence quality and recommendation strength. Consensus was defined as ≥80% agreement (strongly agree or agree) on a 5-point Likert scale. RESULTS: Forty-two statements reached consensus after three rounds of voting. Recommendations included: three statements on training and competency; 10 statements on preresection evaluation, including optical diagnosis, classification, and staging of LSTs; 14 statements on endoscopic resection indications and technique, including statements on en bloc and piecemeal resection decision-making; seven statements on postresection evaluation; and eight statements on postresection care. CONCLUSIONS: An international expert consensus based on the current available evidence has been developed to guide the evaluation, resection, and follow-up of LSTs. This may provide guiding principles for the global management of these lesions and standardize current practices.

Non-conventional dysplasias of the tubular gut: a review and illustration of their histomorphological spectrum.

The increasing use of gastrointestinal endoscopic procedures has led to the recognition by histopathologists of non-conventional (or special-type) dysplasias of the gastrointestinal tract. These lesions can be recognised in association with prevalent underlying gastrointestinal conditions, such as Barrett oesophagus, chronic atrophic gastritis, and inflammatory bowel disease. The diagnosis of these special types can be challenging, and their biological behaviours are not fully characterised. The aim of this review is to provide a global view of non-conventional dysplastic lesions observed in the various segments of the tubular gastrointestinal tract and describe their salient features. Furthermore, as the clinical implications of these various subtypes have not been broadly tested in practice and are not represented in most management guidelines, we offer guidance on the best management practices for these lesions.

Pathology definitions and resection strategies for early colorectal neoplasia: Eastern versus Western approaches in the post-Vienna era.

There is a well-known discrepancy between East and West classifications of colorectal neoplasm, especially "intramucosal carcinoma," categorized as subgroup 4.4 in the Vienna classification, usually recognized as high-grade dysplasia in the United States and as carcinoma in situ in Japan. Focusing on management, in the current National Comprehensive Cancer Network algorithm, high-grade dysplasia, carcinoma in situ, and intramucosal carcinoma are managed similarly, whereas submucosal invasion by carcinoma requires en bloc resection. To bridge the differences with regard to these conceptual problems in the definition and management of carcinoma in situ and intramucosal carcinoma, endoscopists and pathologists from Japan and the United States gathered and discussed from their perspectives how to accurately assess specimens of en bloc/piecemeal resection and to effectively predict lymph node metastasis risk.

Hepatic arterial buffer response: pathologic evidence in non-cirrhotic human liver with extrahepatic portal vein thrombosis.

Increase in hepatic arterial flow in response to reduced portal flow (hepatic arterial buffer response) has been demonstrated experimentally and surgically. We provide pathologic evidence for hepatic arterial buffer response in non-cirrhotic patients with extrahepatic portal vein thrombosis and elucidate the histopathologic spectrum of non-cirrhotic portal vein thrombosis. Liver biopsies and resections from non-cirrhotic patients with extra-hepatic portal vein thrombosis were retrieved. Morphologic features, extent of CD34 staining, outer diameters, luminal diameters and wall thickness of hepatic arteries cut in cross-section and outer diameters of cross-sectioned paired bile ducts were compared with age- and gender-matched controls. There were 12 male and 9 female patients. Measurements of 280 and 193 arteries from patients and controls, respectively, demonstrated statistically significant (P<0.05) arterial dilatation (increase in percentage of arterial lumen to outer diameter) and arterial wall thinning in resection specimens of non-cirrhotic patients with extra-hepatic portal vein thrombosis. Subtle and/or focal dilatation of central veins, portal veins and sinusoids; focal trabecular thinning/thickening and mild ductular reaction were common findings in both the patient and control groups. Diffuse and obvious changes, and portal vein absence or attenuation were seen only in the patient group. Capillarization of sinusoids was not seen on CD34 stain. Two patients showed significant ductular reaction, one of who developed biliary strictures on follow-up. Hepatic arterial dilatation and wall thinning in non-cirrhotic patients with portal vein thrombosis provide pathologic evidence of hepatic arterial buffer response in the human liver. Obvious and diffuse sinusoidal dilatation and absence or attenuation of portal veins are highly suggestive of extrahepatic portal vein thrombosis in non-cirrhotic patients with portal hypertension. Periportal shunt vessels, hypervascular portal tracts, muscularized portal veins, large thick-walled or dilated arteries aid diagnosis but are rare findings. Normal or near-normal biopsies do not rule out portal vein thrombosis.

Blastomas of the digestive system in adults: A review.

Blastomas, characterized by a mixture of mesenchymal, epithelial, and undifferentiated blastematous components, are rare malignant neoplasms originating from precursor blast cells. This review focuses on digestive system blastomas in adult patients, including gastroblastoma, hepatoblastoma, and pancreatoblastoma. Gastroblastoma is a biphasic, epitheliomesenchymal tumor, with only sixteen cases reported to date. In addition to the characteristic histology, metastasis-associated lung adenocarcinoma transcript 1 - glioma-associated oncogene homolog 1 gene fusion is typical, although recently novel ewing sarcoma breakpoint region 1 - c-terminal binding protein 1 and patched 1 - glioma-associated oncogene homolog 2 fusions have been described. Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty. Pancreatoblastoma, primarily a pediatric tumor, displays acinar differentiation and squamoid nests with other lines of differentiation also present, especially neuroendocrine. Diagnostic approaches for these blastomas include a combination of imaging modalities, histopathological examination, and molecular profiling. The treatment generally involves surgical resection, which may be supplemented by chemotherapy or radiotherapy in some cases. Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes, particularly in the setting of metastases. This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

A Case of Hepatic Malignant Solitary Fibrous Tumor: A Case Report and Review of the Literature.

A 73-year-old man with a history of atrial myxoma and basal cell carcinoma presented with unexplained fever. Contrast-enhanced CT abdomen showed a large left hepatic lobe mass with early enhancement and delayed venous washout, concerning for hepatocellular carcinoma. Fine needle aspiration showed numerous spindle cells with malignant nuclear features, suggestive of malignant spindle cell neoplasm. The patient underwent left hepatectomy. The surgical specimen showed a well-circumscribe solid mass (14.6 × 13.0 × 10.0 cm) with necrosis. Histopathological examination revealed a proliferation of spindle tumor cells with characteristic staghorn-shaped blood vessels, frequent mitoses, and necrosis. The tumor cells showed strong and diffuse expression of CD34 and STAT6, confirming the diagnosis of malignant solitary fibrous tumor. Solitary fibrous tumor is a rare fibroblastic tumor characterized by a staghorn vasculature and NAB2-STAT6 gene rearrangement. Solitary fibrous tumor of the liver is a rare occurrence. Although most solitary fibrous tumors behave in a benign fashion, solitary fibrous tumors might act aggressively. This case is unique in that it demonstrates an excellent correlation between radiologic, macroscopic, and microscopic features which can contribute to the improvement of radiologic and pathologic diagnostic accuracy.

Route and antigen shape immunity to dmLT-adjuvanted vaccines to a greater extent than biochemical stress or formulation excipients.

A key aspect to vaccine efficacy is formulation stability. Biochemical evaluations provide information on optimal compositions or thermal stability but are routinely validated by ex vivo analysis and not efficacy in animal models. Here we assessed formulations identified to improve or reduce stability of the mucosal adjuvant dmLT being investigated in polio and enterotoxigenic E. coli (ETEC) clinical vaccines. We observed biochemical changes to dmLT protein with formulation or thermal stress, including aggregation or subunit dissociation or alternatively resistance against these changes with specific buffer compositions. However, upon injection or mucosal vaccination with ETEC fimbriae adhesin proteins or inactivated polio virus, experimental findings indicated immunization route and co-administered antigen impacted vaccine immunogenicity more so than dmLT formulation stability (or instability). These results indicate the importance of both biochemical and vaccine-derived immunity assessment in formulation optimization. In addition, these studies have implications for use of dmLT in clinical settings and for delivery in resource poor settings.

Assessment of Elastic Laminal Invasion Contributes to an Objective pT3 Subclassification in Colon Cancer.

The extent of tumor spread influences on the clinical outcome, and which determine T stage of colorectal cancer. However, pathologic discrimination between pT3 and pT4a in the eighth edition of the American Joint Committee on Cancer (AJCC)-TNM stage is subjective, and more objective discrimination method for deeply invasive advanced colon cancer is mandatory for standardized patient management. Peritoneal elastic laminal invasion (ELI) detected using elastic staining may increase the objective discrimination of deeply invasive advanced colon cancer. In this study, we constructed ELI study group to investigate feasibility, objectivity, and prognostic utility of ELI. Furthermore, pT classification using ELI was investigated based on these data. At first, concordance study investigated objectivity using 60 pT3 and pT4a colon cancers. Simultaneously, a multi-institutional retrospective study was performed to assess ELI's prognostic utility in 1202 colon cancer cases from 6 institutions. In the concordance study, objectivity, represented by κ, was higher in the ELI assessment than in pT classification. In the multi-institutional retrospective study, elastic staining revealed that ELI was a strong prognostic factor. The clinical outcome of pT3 cases with ELI was significantly and consistently worse than that of those without ELI. pT classification into pT3 without ELI, pT3 with ELI, and pT4a was an independent prognostic factor. In this study, we revealed that ELI is an objective method for discriminating deeply invasive advanced colon cancer. Based on its feasibility, objectivity, and prognostic utility, ELI can subdivide pT3 lesions into pT3a (without ELI) and pT3b (with ELI).

A Case of Esophageal Squamous Cell Carcinoma Metastasized to the Colonic Anastomotic Site of Right Hemicolectomy.

A 73-year-old woman with a history of right hemicolectomy for advanced ascending colon cancer 14 years earlier was referred to our facility for a 2-month history of solid food dysphagia. An esophagogastroduodenoscopy revealed a 7-cm fungating and ulcerated mass in the middle to lower esophagus. The biopsy from the esophageal mass showed a moderately to poorly differentiated squamous cell carcinoma. A colonoscopy showed an end-to-end ileocolonic anastomosis with a 7-mm ulceration in the transverse colon. The biopsy of the ulceration at the anastomotic site showed a moderately to poorly differentiated squamous cell carcinoma with a morphology similar to that of the esophageal mass, rendering the diagnosis of metastatic esophageal squamous cell carcinoma. Colonic metastasis from esophageal squamous cell carcinoma, especially at the anastomotic site, is extremely rare. Although surgical trauma may not have contributed to the anastomotic site metastasis, given the distant timeline, its role in the pathogenesis of metastasis cannot be completely ruled out.

Multicenter prospective in vivo study of an endocytoscope system (ECS) for superficial esophageal cancer.

BACKGROUND: Endocytoscope systems (ECS) can visualize cellular nuclei of the mucosa of the gastrointestinal tract and are predicted to provide real-time microscopic diagnosis. However, their practical diagnostic performance remains unclear. Therefore, we conducted a multicenter prospective study to evaluate the visualization of superficial esophageal neoplasm in vivo using an ECS, and its diagnostic capability. METHODS: The study target was histologically confirmed squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN). An integrated ECS was used to obtain ECS images. In each patient, three ECS images of cancerous and corresponding noncancerous regions were selected for evaluation. A pathological review board of five certified pathologists made the final diagnosis of the images. The primary endpoint was the sensitivity of ECS diagnosis by pathologists. RESULTS: ECS images of 68 patients were assessed: 42 lesions were mucosal SCC, 13 were submucosal SCC, and 13 were HGIN. The rate of assessable images was 96% (95% CI 87.6-99.1). The sensitivity of ECS diagnosis by pathologists was 88% (95% CI 77.2-94.5). CONCLUSIONS: ECS can provide high-quality images of cancerous lesions and a high diagnostic accuracy by pathologists, and could be useful for real-time endoscopic histological diagnosis of SCC and HGIN. TRIAL REGISTRATION: The UMIN Clinical Trials Registry Identification Number: 000004218.

Pathological prognostic factors predicting lymph node metastasis in submucosal invasive (T1) colorectal carcinoma.

Lymph node metastasis occurs in as many as 16% of patients with submucosal invasive colorectal carcinoma. We investigated the association between histopathological factors and lymph node metastases in 322 consecutive patients with submucosal invasive colorectal carcinoma who had undergone radical colectomy with lymph node dissection to detect patients at high risk of lymph node metastasis without measuring the depth of submucosal invasion. Lymph node metastasis was found in 46 (14.3%) of 322 patients with submucosal invasive colorectal carcinoma. Univariate analysis showed that each of the following histopathological factors had a significant influence on lymph node metastasis: invasion depth, lymphatic invasion, venous invasion, tumor differentiation, growth pattern of the intramucosal tumor component, complete disruption of the muscularis mucosa due to tumor invasion, and tumor budding at the submucosal invasive front. Multivariate analysis showed that lymphatic invasion (P<0.01), tumor differentiation (P<0.01), and tumor budding (P<0.01) were significantly associated with lymph node metastasis. All 46 cases of lymph node metastasis showed at least one of the following findings: lymphatic invasion, moderately or poorly differentiated tumor grade, tumor budding, or complete disruption of the muscularis mucosa due to tumor invasion. Patients with submucosal invasive colorectal carcinoma that show at least one of three factors--lymphatic invasion, moderately or poorly differentiated tumor grade, or tumor budding--are at high risk for lymph node metastasis. All of the patients with lymph node metastasis, who did not have any of these factors, showed a completely disrupted muscularis mucosa.

Transglutaminase 3 as a prognostic biomarker in esophageal cancer revealed by proteomics.

To develop a prognostic biomarker for esophageal squamous cell carcinoma (ESCC), we examined the proteomic profile of ESCC using two-dimensional difference gel electrophoresis (2D-DIGE), and identified proteins associated with prognosis by mass spectrometry. The prognostic performance of the identified proteins was examined by immunohistochemistry in additional cases. We identified 22 protein spots whose intensity was statistically different between ESCC cases with good (N = 9; survived more than 5 years without evidence of recurrence) and poor (N = 24; died within 2 years postsurgery) prognosis, within the patient group that had two or more lymph node metastases. Mass spectrometric protein identification resulted in 18 distinct gene products from the 22 protein spots. Transglutaminase 3 (TGM3) was inversely correlated with shorter patient survival. The prognostic performance of TGM3 was further examined by immunohistochemistry in 76 ESCC cases. The 5-year disease-specific survival rate was 64.5% and 32.1% for patients with TGM3-positive and TGM3-negative tumors, respectively (p = 0.0033). Univariate and multivariate analyses revealed that TGM3 expression was an independent prognostic factor among the clinicopathologic variables examined. It is noteworthy that the prognostic value of TGM3 was shown to be higher than those of the lymph node metastasis, intramural metastasis and vascular invasion status. These results establish TGM3 as a novel prognostic biomarker for ESCC for the first time. Examination of TGM3 expression may provide novel therapeutic strategies to prevent recurrence of ESCC.

Antibody-based proteomics for esophageal cancer: Identification of proteins in the nuclear factor-kappaB pathway and mitotic checkpoint.

To identify the molecular background of esophageal cancer, we conducted a proteomics study using an antibody microarray consisting of 725 antibodies and surgical specimens from three cases. The microarray analysis identified 24 proteins with aberrant expression in esophageal cancer compared with the corresponding normal mucosa. The overexpression of 14 of the 24 proteins was validated by western blotting analysis of the same samples. These 14 proteins were examined by immunohistochemistry, in which nine proteins showed consistent results with those obtained by western blotting. Among the nine proteins, seven were localized in tumor cells, and two in infiltrating cells. The former included proteins associated with mitotic checkpoint control and the nuclear factor (NF)-kappaB pathway. Although mitotic checkpoint gene products (budding uninhibited by benzidazoles 1 homolog beta (BubR1) and mitotic arrest deficient-like 1 (Mad2)) have previously been reported to be involved in esophageal cancer, the association of NF-kappaB-activating kinase, caspase 10, and activator protein-1 with esophageal cancer has not been previously reported. These proteins play a key role in the NF-kappaB pathway, and NF-kappaB is a signal transduction factor that has emerged as an important modulator of altered gene programs and malignant phenotype in the development of cancer. The association of these proteins with esophageal cancer may indicate that mitotic checkpoint gene products and NF-kappaB play an important part in the carcinogenesis of esophageal cancer.

Quantitative proteomics using formalin-fixed paraffin-embedded tissues of oral squamous cell carcinoma.

Clinical proteomics using a large archive of formalin-fixed paraffin-embedded (FFPE) tissue blocks has long been a challenge. Recently, a method for extracting proteins from FFPE tissue in the form of tryptic peptides was developed. Here we report the application of a highly sensitive mass spectrometry (MS)-based quantitative proteome method to a small amount of samples obtained by laser microdissection from FFPE tissues. Cancerous and adjacent normal epithelia were microdissected from FFPE tissue blocks of 10 squamous cell carcinomas of the tongue. Proteins were extracted in the form of tryptic peptides and analyzed by 2-dimensional image-converted analysis of liquid chromatography and mass spectrometry (2DICAL), a label-free quantitative proteomics method developed in our laboratory. From a total of 25 018 peaks we selected 72 mass peaks whose expression differed significantly between cancer and normal tissues (P < 0.001, paired t-test). The expression of transglutaminase 3 (TGM3) was significantly down-regulated in cancer and correlated with loss of histological differentiation. Hypermethylation of TGM3 gene CpG islands was observed in 12 oral squamous cell carcinoma (OSCC) cell lines with reduced TGM3 expression. These results suggest that epigenetic silencing of TGM3 plays certain roles in the process of oral carcinogenesis. The method for quantitative proteomic analysis of FFPE tissue described here offers new opportunities to identify disease-specific biomarkers and therapeutic targets using widely available archival samples with corresponding detailed pathological and clinical records.

CUB-domain-containing protein 1 regulates peritoneal dissemination of gastric scirrhous carcinoma.

CUB-domain-containing protein 1 (CDCP1) is a type-I transmembrane protein that is highly expressed in colon, breast, and lung cancers. We recently revealed that CDCP1 is associated with and phosphorylated by Src family kinases and is involved in the regulation of anchorage independence of certain lung cancer cell lines. In this study, we examined whether CDCP1 is involved in the regulation of tumor progression of scirrhous gastric cancer, which is a diffusely infiltrative carcinoma with high invasion potential. Expression and phosphorylation levels of CDCP1 correlated with the invasive potential of scirrhous gastric cancers. Reduction of CDCP1 expression by siRNA suppressed migration, invasion, and anchorage independence without affecting the proliferation of highly invasive scirrhous gastric cancer cells. However, CDCP1 overexpression promoted gastric cancer cell migration with low potential of invasion. Loss of CDCP1 suppressed invasion and dissemination of cancer cells that were orthotopically implanted in the gastric wall of nude mice. Expression and phosphorylation of CDCP1 were also detected in cancer cells of surgically resected tissues of human scirrhous gastric cancer by immunohistochemical analysis. Our results suggest that CDCP1 promotes invasion and peritoneal dissemination of cancer cells through the regulation of cell migration and anchorage independence. Therefore, it is both a potential prognostic and therapeutic target in certain types of gastrointestinal cancers, and suppression of its phosphorylation might be a useful strategy for modulating cancer metastasis.

Podoplanin expression identified in stromal fibroblasts as a favorable prognostic marker in patients with colorectal carcinoma.

OBJECTIVE: The microenvironment of cancer plays a critical role in its progression. However, the molecular features of cancer-associated fibroblasts (CAFs) are less well understood than those of cancer cells. We investigated the clinicopathological significance of podoplanin expression in stromal fibroblasts in patients with colorectal cancer (CRC). METHODS: We selected podoplanin as an upregulated marker in CAF from a DNA microarray experiment. Consequently, podoplanin was identified as an upregulated gene. Immunohistochemical podoplanin expression was investigated at the National Cancer Center Hospital, Tokyo, Japan, in 120 patients with advanced CRC, and its clinicopathological significance was examined. The biological function of podoplanin expression was also assessed by a coculture invasion assay with CRC cell lines such as HCT116 and HCT15. RESULTS: Podoplanin expression was exclusively confined to stromal fibroblasts and absent in tumor cells. Podoplanin is absent in normal stroma except for lymphatic vessels. Staining was considered positive when over 30% of the cancer stroma was stained. Positive podoplanin expression was significantly correlated with a more distal tumor localization (p = 0.013) and a shallower depth of tumor invasion (p = 0.011). Univariate analysis revealed that negative podoplanin expression in stromal fibroblasts was significantly associated with reduced disease-specific survival (p = 0.0017) and disease-free survival (p < 0.0001). Multivariate analysis revealed that negative podoplanin expression (p = 0.016) and lymph node metastasis (p = 0.027) were significantly associated with disease-free survival. CRC cell invasion was augmented by co-culture with CAFs that were treated with siRNA for podoplanin. CONCLUSIONS: Our results suggest that a positive podoplanin expression in stromal fibroblasts could have a protective role against CRC cell invasion and is a significant indicator of a good prognosis in patients with advanced CRC, supported by biological analysis showing that podoplanin expression in CAFs is associated with decreased CRC cell invasion.

Esophageal melanomas harbor frequent NRAS mutations unlike melanomas of other mucosal sites.

Mucosal melanomas have genetic alterations distinct from those in cutaneous melanomas. For example, NRAS- and BRAF-activating mutations occur frequently in cutaneous melanomas, but not in mucosal melanomas. We examined 16 esophageal melanomas for genetic alterations in NRAS, BRAF, and KIT to determine whether they exhibit genetic features common to melanomas arising from other mucosal sites. A sequencing analysis identified NRAS mutations in six cases; notably, four of these mutations were located in exon 1, an uncommon mutation site in cutaneous and other mucosal melanomas. BRAF and KIT mutations were found in one case each. Immunohistochemistry showed KIT expression in four cases, including the tumor with a KIT mutation and two other intramucosal tumors. The low frequency of BRAF mutations and the presence of a KIT mutation-positive case are findings similar to those of mucosal melanomas of other sites, but the prevalence of NRAS mutations was even higher than that of cutaneous melanomas. The present study implies that esophageal melanomas have genetic alterations unique from those observed in other mucosal melanomas.

Lymph node staging in esophageal squamous cell carcinoma: a comparative study of endoscopic ultrasonography versus computed tomography.

BACKGROUND AND AIM: Endoscopic ultrasonography (EUS) is established as a standard approach for locoregional staging of esophageal cancer. However, only a few published studies have attempted to correlate the station of the abnormal lymph nodes detected by EUS with the definitive histology. We compared EUS and computed tomography (CT) in the initial staging of esophageal squamous cell carcinoma. METHODS: Consecutive patients with esophageal cancer undergoing EUS were evaluated. EUS findings and patient data including histopatology were collected prospectively and analyzed retrospectively. Lymph node locations were divided into three groups; abdominal (A), paraesophageal (B), and thoracic paratracheal (C). RESULTS: A total of 365 consecutive patients underwent EUS and 159 patients underwent esophagectomy without neoadjuvant chemotherapy. Thirty-eight patients were excluded (insufficient EUS, etc.), and 121 patients were enrolled. The overall accuracy of EUS was 64% (sensitivity 68%, specificity 58%, positive predictive value [PPV] 68%), CT was 51% (sensitivity 33%, specificity 75%, PPV 64%), and CT + EUS was 64% (sensitivity 74%, specificity 50%, PPV 66%). The accuracy of EUS was higher than CT in Groups A and C. Sensitivity of CT was lower than that of EUS alone and CT + EUS. CONCLUSIONS: This study has demonstrated that EUS is a more accurate technique than contrast-enhanced CT for detecting abnormal lymph nodes. Sensitivity of CT was lower than that of EUS alone and CT + EUS. But some metastatic lymph nodes in neck and abdominal fields are only detectable by CT. Therefore, both EUS and CT should be undertaken for routine examination prior to treatment of esophageal cancer.

Clear cell adenocarcinoma of the lung: a SEER analysis.

Clear cell adenocarcinoma (CCA) in lung has been considered as a rare subtype of lung adenocarcinoma. However, recent classifications of lung adenocarcinoma proposed to discontinue CCA due to lack of available data with clinical significance. Patients with CCA and lung adenocarcinoma not otherwise specified (LANOS) were queried from The Surveillance, Epidemiology, and End Results Program (SEER) database. Cancer-specific survival was studied according to gender (male, female), age (0-69, 70+), SEER specific stage A system (localized, regional and distant), year of diagnosis (1973-2000, 2001-2013), surgery (yes, no), and radiation therapy (yes, no) using Kaplan-Meier curves. Multivariate analysis was used to study independent predictors of cancer-specific survival. A total of 1,227 and 233,154 patients with the diagnosis of CCA and LANOS respectively were found in the SEER database. CCA histology was significantly associated with an early year of diagnosis, younger age, early stage, surgery, and lack of radiation. Kaplan-Meier curves showed that patients with CCA histology had significantly better cancer-specific survival (P<0.0001, Log-Rank). Subset analysis demonstrated the difference in cancer-specific survival between CCA and NOS histology was significant in localized and regional but not distant stage disease (P=0.0453, 0.0009, 0.0664, respectively). Patients with CCA histology have superior survival in the locoregional stage according to our SEER analysis, suggesting its unique role in prognosis despite it being removed from recent pathologic classifications.

Strongyloides stercoralis Hyperinfection Syndrome as a Cause of Fatal Gastrointestinal Hemorrhage.

Strongyloides stercoralis is a small intestinal nematode that is widespread in regions with poor sanitation. We present a 57-year-old man from Colombia who was undergoing corticosteroid therapy for a meningioma who presented after neurosurgery with abdominal pain and a profound gastrointestinal (GI) bleed. The patient underwent an esophagogastroduodenoscopy (EGD), an attempted embolization, and an exploratory laparotomy to remove the necrosed duodenum. His pathology examination revealed Strongyloides infection of the duodenum, and he died of profound blood loss. This rare diagnosis displays the importance of screening patients at a high risk of Strongyloides infection before starting glucocorticoid therapy.