Vitiligo is a disease that results in depigmented areas in the skin. It may develop at any age but the average age at onset is 20 years. Association of vitiligo and melanoma has been commonly reported, but malignancies other than melanoma have been rarely associated with vitiligo. We report a 73-year-old patient with new onset vitiligo who developed esophageal adenocarcinoma in the following years.
Asilian, Ali; Momeni, Iman; Khosravani, Parastou
The incidence of esophageal adenocarcinoma (EA) and its precursor condition, Barrett's esophagus, has risen rapidly in the United States for reasons that are not fully understood. Therefore, we evaluated the association between use of supplemental vitamins and minerals and risk of neoplastic progression of Barrett's esophagus and EA. The Seattle Barrett's Esophagus Program is a prospective study based on 339
Linda M. Dong; Alan R. Kristal; Ulrike Peters; Jeannette M. Schenk; Carissa A. Sanchez; Peter S. Rabinovitch; Patricia L. Blount; Robert D. Odze; Kamran Ayub; Brian J. Reid; Thomas L. Vaughan
Objective To document what can be accomplished with surgical resection done according to the classical principles of surgical oncology. Methods One hundred consecutive patients underwent en bloc esophagectomy for esophageal adenocarcinoma. No patient received pre- or postoperative chemotherapy or radiation therapy. Tumor depth and number and location of involved lymph nodes were recorded. A lymph node ratio was calculated by dividing the number of involved nodes by the total number removed. Follow-up was complete in all patients. The median follow-up of surviving patients was 40 months, with 23 patients surviving 5 years or more. Results The overall actuarial survival rate at 5 years was 52%. Survival rates by American Joint Commission on Cancer (AJCC) stage were stage 1 (n = 26), 94%; stage 2a (n = 11), 65%; stage 2b (n = 13), 65%; stage 3 (n = 32), 23%; and stage 4 (n = 18), 27%. Sixteen tumors were confined to the mucosa, 16 to the submucosa, and 13 to the muscularis propria, and 55 were transmural. Tumor depth and the number and ratio of involved nodes were predictors of survival. Metastases to celiac (n = 16) or other distant node sites (n = 26) were not associated with decreased survival. Local recurrence was seen in only one patient. Latent nodal recurrence outside the surgical field occurred in 9 patients and systemic metastases in 31. Tumor depth, the number of involved nodes, and the lymph node ratio were important predictors of systemic recurrence. The surgical death rate was 6%. Conclusion Long-term survival from adenocarcinoma of the esophagus can be achieved in more than half the patients who undergo en bloc resection. One third of patients with lymph node involvement survived 5 years. Local control is excellent after en bloc resection. The extent of disease associated with tumors confined to the mucosa and submucosa provides justification for more limited and less morbid resections.
Hagen, Jeffrey A.; DeMeester, Steven R.; Peters, Jeffrey H.; Chandrasoma, Para; DeMeester, Tom R.
Answer questions and earn CME/CNE Esophageal adenocarcinoma (EAC) is characterized by 6 striking features: increasing incidence, male predominance, lack of preventive measures, opportunities for early detection, demanding surgical therapy and care, and poor prognosis. Reasons for its rapidly increasing incidence include the rising prevalence of gastroesophageal reflux and obesity, combined with the decreasing prevalence of Helicobacter pylori infection. The strong male predominance remains unexplained, but hormonal influence might play an important role. Future prevention might include the treatment of reflux or obesity or chemoprevention with nonsteroidal antiinflammatory drugs or statins, but no evidence-based preventive measures are currently available. Likely future developments include endoscopic screening of better defined high-risk groups for EAC. Individuals with Barrett esophagus might benefit from surveillance, at least those with dysplasia, but screening and surveillance strategies need careful evaluation to be feasible and cost-effective. The surgery for EAC is more extensive than virtually any other standard procedure, and postoperative survival, health-related quality of life, and nutrition need to be improved (eg, by improved treatment, better decision-making, and more individually tailored follow-up). Promising clinical developments include increased survival after preoperative chemoradiotherapy, the potentially reduced impact on health-related quality of life after minimally invasive surgery, and the new endoscopic therapies for dysplastic Barrett esophagus or early EAC. The overall survival rates are improving slightly, but poor prognosis remains a challenge. CA Cancer J Clin 2013. © 2013 American Cancer Society. PMID:23584949
Lagergren, Jesper; Lagergren, Pernilla
Answer questions and earn CME/CNE Esophageal adenocarcinoma (EAC) is characterized by 6 striking features: increasing incidence, male predominance, lack of preventive measures, opportunities for early detection, demanding surgical therapy and care, and poor prognosis. Reasons for its rapidly increasing incidence include the rising prevalence of gastroesophageal reflux and obesity, combined with the decreasing prevalence of Helicobacter pylori infection. The strong male predominance remains unexplained, but hormonal influence might play an important role. Future prevention might include the treatment of reflux or obesity or chemoprevention with nonsteroidal antiinflammatory drugs or statins, but no evidence-based preventive measures are currently available. Likely future developments include endoscopic screening of better defined high-risk groups for EAC. Individuals with Barrett esophagus might benefit from surveillance, at least those with dysplasia, but screening and surveillance strategies need careful evaluation to be feasible and cost-effective. The surgery for EAC is more extensive than virtually any other standard procedure, and postoperative survival, health-related quality of life, and nutrition need to be improved (eg, by improved treatment, better decision-making, and more individually tailored follow-up). Promising clinical developments include increased survival after preoperative chemoradiotherapy, the potentially reduced impact on health-related quality of life after minimally invasive surgery, and the new endoscopic therapies for dysplastic Barrett esophagus or early EAC. The overall survival rates are improving slightly, but poor prognosis remains a challenge. PMID:23818335
Lagergren, Jesper; Lagergren, Pernilla
Ubiquitin-dependent proteolysis of cyclins plays a criti- cal role in cell cycle progression and tumorigenesis. We examined the expression of ubiquitin-conjugating enzymeE2C(UBE2C)duringprogressionfromBarrett's metaplasia to esophageal adenocarcinoma (EA) and the effects of targeting this enzyme on EA-derived cell lines. Using oligonucleotide microarrays UBE2C ex- pression was elevated in 73% (11 of 15) of EAs relative to Barrett's metaplasia. Tissue microarray showed
Jules Lin; Duna A. Raoof; Zhuwen Wang; Mu-Yen Lin; Dafydd G. Thomas; Joel K. Greenson; Thomas J. Giordano; Mark B. Orringer; Andrew C. Chang; David G. Beer; Lin Lin
Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors. It is possible that a difference in the expression of estrogen, or its signaling axes, may contribute to this gender bias. We undertook a comprehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expression, and the possible sex-specific links with esophageal adenocarcinoma development. Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression, and the effect of crosstalk between estrogen and leptin signaling were identified. We also found limited studies suggesting a role for estrogen receptor ? expression in esophageal adenocarcinoma development. The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcinoma, but further studies are required.
Yang, Huiqi; Sukocheva, Olga A; Hussey, Damian J; Watson, David I
Carbonated soft drinks (CSDs) have been associated with gastroesophageal refl ux, an established risk factor for esophageal adenocarcinoma. As both CSD consumption and esophageal ade- nocarcinoma incidence have sharply increased in recent decades, we exam- ined CSD as a risk factor for esophageal and gastric cancers in a U.S. multi- center, population-based case-control study. Associations between CSD intake and risk
Susan T. Mayne; Harvey A. Risch; Robert Dubrow; Wong-Ho Chow; Marilie D. Gammon; Thomas L. Vaughan; Lauren Borchardt; Janet B. Schoenberg; Janet L. Stanford; A. Brian West; Heidi Rotterdam; William J. Blot; Joseph F. Fraumeni
Background and aims Alcohol intake is a strong and well-established risk factor for esophageal squamous cell carcinoma (ESCC), but the association with esophageal adenocarcinoma (EA) or adjacent tumors of the esophagogastric junction (EGJA), remains unclear. Therefore, we determined the association of alcohol intake with ESCC, EA, and EGJA in nine case-control studies and two cohort studies of the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON). Materials and methods We collected information on alcohol intake, age, sex, education, body mass index, gastroesophageal reflux, and tobacco smoking from each study. Along with 10,854 controls, 1,821 EA, and 1,837 EGJA, seven studies also collected ESCC cases (n=1,016). Study-specific odds ratios (OR) and 95% confidence intervals (CI) were calculated from multivariate-adjusted logistic regression models for alcohol intake in categories compared to non-drinkers. Summary risk estimates were obtained by random effects models. Results We observed no increase in risk of EA or EGJA for increasing levels of any of the alcohol intake measures examined. ORs for the highest frequency category (?7 drinks per day) were 0.97 (95% CI = 0.68-1.36) for EA and 0.77 (95% CI = 0.54-1.10) for EGJA. Suggestive findings linked moderate intake (e.g. 0.5 to <1 drinks per day) to decreased risk of EA (OR = 0.63 95% CI = 0.41-0.99) and EGJA (OR = 0.78; 95% CI = 0.62-0.99). In contrast, alcohol intake was strongly associated with increased risk of ESCC (OR for ?7 drinks per day= 9.62, 95%CI=4.26-21.71). Conclusions In contrast to ESCC, higher alcohol consumption was not associated with increased risk of either EA or EGJA. The apparent inverse association observed with moderate alcohol intake should be evaluated in future prospective studies.
Freedman, Neal D; Murray, Liam J; Kamangar, Farin; Abnet, Christian C; Cook, Michael B; Nyren, Olof; Ye, Weimin; Wu, Anna H; Bernstein, Leslie; Brown, Linda M; Ward, Mary H; Pandeya, Nirmala; Green, Adele; Casson, Alan G; Giffen, Carol; Risch, Harvey A; Gammon, Marilie D; Chow, Wong-Ho; Vaughan, Thomas L; Corley, Douglas A; Whiteman, David C
Gastroesophageal reflux disease is a risk factor for esophageal adenocarcinoma yet studies that have investigated the relationship between erosive esophagitis and esophageal adenocarcinoma have usually focused on symptom-related evidence or polymorphisms. There are no epigenetic gene expression studies on this topic. In this study, we aimed to evaluate the relationship between erosive esophagitis and esophageal adenocarcinoma to identify whether there is a genetic predisposition for esophageal adenocarcinoma. The Human Epigenetic Chromatin Modification Enzyme RT(2) Profiler(™) PCR array (PAHS-085A) was used to detect the expression of 84 key genes encoding enzymes. This was carried out prospectively for samples from 60 patients (20 patients as a control group, 20 patients with erosive esophagitis and 20 patients with esophageal adenocarcinoma). AURKA, AURKB, NEK6 were expressed at significantly higher levels in esophageal adenocarcinoma compared to the control group. MBD2 was expressed at significantly lower levels in the esophageal adenocarcinoma group compared to the control group. AURKA, AURKC, HDAC9 and NEK6 were expressed at significantly higher levels in erosive esophagitis compared to the control group. There was no difference in upregulated gene expression between the erosive esophagitis and esophageal adenocarcinoma. MBD2 was significantly downregulated in esophageal adenocarcinoma compared to erosive esophagitis. NEK6 and AURKA were significantly upregulated in esophageal adenocarcinoma and erosive esophagitis compared to the control group. This is a novel study on the genetic predisposition for erosive esophagitis and esophageal adenocarcinoma. AURKA and NEK6 are two promising genetic markers for erosive esophagitis and esophageal adenocarcinoma. PMID:23060919
Kasap, Elmas; Boyacioglu, Seda Örenay; Korkmaz, Mehmet; Yuksel, Elif Saritas; Unsal, Belkis; Kahraman, Erkan; Ozütemiz, Omer; Yuceyar, Hakan
Gastroesophageal reflux disease is a risk factor for esophageal adenocarcinoma yet studies that have investigated the relationship between erosive esophagitis and esophageal adenocarcinoma have usually focused on symptom-related evidence or polymorphisms. There are no epigenetic gene expression studies on this topic. In this study, we aimed to evaluate the relationship between erosive esophagitis and esophageal adenocarcinoma to identify whether there is a genetic predisposition for esophageal adenocarcinoma. The Human Epigenetic Chromatin Modification Enzyme RT2 Profiler™ PCR array (PAHS-085A) was used to detect the expression of 84 key genes encoding enzymes. This was carried out prospectively for samples from 60 patients (20 patients as a control group, 20 patients with erosive esophagitis and 20 patients with esophageal adenocarcinoma). AURKA, AURKB, NEK6 were expressed at significantly higher levels in esophageal adenocarcinoma compared to the control group. MBD2 was expressed at significantly lower levels in the esophageal adenocarcinoma group compared to the control group. AURKA, AURKC, HDAC9 and NEK6 were expressed at significantly higher levels in erosive esophagitis compared to the control group. There was no difference in upregulated gene expression between the erosive esophagitis and esophageal adenocarcinoma. MBD2 was significantly downregulated in esophageal adenocarcinoma compared to erosive esophagitis. NEK6 and AURKA were significantly upregulated in esophageal adenocarcinoma and erosive esophagitis compared to the control group. This is a novel study on the genetic predisposition for erosive esophagitis and esophageal adenocarcinoma. AURKA and NEK6 are two promising genetic markers for erosive esophagitis and esophageal adenocarcinoma.
KASAP, ELMAS; BOYACIOGLU, SEDA ORENAY; KORKMAZ, MEHMET; YUKSEL, ELIF SARITAS; UNSAL, BELKIS; KAHRAMAN, ERKAN; OZUTEMIZ, OMER; YUCEYAR, HAKAN
The overexpression of AXL receptor tyrosine kinase is a frequent finding that has been associated with poor prognosis in esophageal adenocarcinoma (EAC). As the majority of EAC are intrinsically resistant to DNA-damaging therapies, an alternative therapeutic approach based on the activation of death receptors may be warranted. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been evaluated in clinical trials and found promising as anticancer agent with mild side effects; unfortunately, resistance to TRAIL remains a major clinical problem. Herein, we explored the role of AXL in TRAIL resistance and elucidated the underlying mechanism. Overexpression of AXL in OE33 and OE19 cells promoted cell survival and attenuated TRAIL-induced cellular and molecular markers of apoptosis. In contrast, knockdown of endogenous AXL sensitized FLO-1 cells to TRAIL. The mechanism by which AXL regulates TRAIL resistance was examined. Protein and mRNA expression of DR4 and DR5 death receptors was not downregulated by AXL. In addition, the possible involvement of FLICE-inhibitory protein (FLIP) in regulating the interaction of caspase-8 with Fas-associated death domain protein (FADD) was excluded, as AXL did not enhance FLIP expression or FLIP/FADD association. Alternatively, protein association of AXL with DR5, independent of TRAIL, was confirmed, suggesting that AXL could regulate DR5 receptor activity. The AXL/DR5 association had no negative effect on TRAIL-induced interaction with FADD. However, the AXL/DR5 interaction blocked the recruitment of caspase-8 to the death-inducing signal complex (DISC). Collectively, our findings uncover a novel mechanism of TRAIL resistance mediated by AXL through regulation of the DISC and provide strong evidence that AXL could be exploited as a therapeutic target to circumvent TRAIL resistance. PMID:23479507
Hong, Jun; Belkhiri, Abbes
OBJECTIVES:The insulin-like growth factor (IGF) pathway and visceral obesity have been independently linked with esophageal cancer. This study aimed to delineate the differential and interlinked role of visceral obesity and the IGF-1 system in esophageal adenocarcinoma and esophageal squamous-cell carcinoma (SCC).METHODS:IGF-1 receptor (IGF-1R) mRNA and protein were examined in esophageal SCC (KYSE 410, OE21) and esophageal adenocarcinoma (OE19, OE33) cell
Suzanne L Doyle; Claire L Donohoe; Stephen P Finn; Julia M Howard; Fiona E Lithander; John V Reynolds; Graham P Pidgeon; Joanne Lysaght
Alpha-fetoprotein (AFP)-producing esophageal tumors are extremely rare. We report herein the case of a 51-year-old man found to have an AFP-producing adenocarcinoma arising from esophageal proper mucosa. The patient presented for investigation of dysphagia, and esophagogram and endoscopy revealed a lesion about 2 cm in size with a depressed center surrounded by low nodular protrusions in the lower esophagus. The preoperative serum AFP concentration was elevated to 52.4 ng/ml. A subtotal esophagectomy was performed, and macroscopic examination of the resected specimen revealed a superficial protruding lesion. Histopathological studies showed a poorly differentiated adenocarcinoma with a single lymph node metastasis. The tumor had infiltrated the submucosal layer, but there was no evidence of lymphatic or venous invasion. Immunohistochemical study revealed tumor cells positive for AFP. There were no findings of Barrett's epithelium or any mucosal changes due to reflux esophagitis. An elevated AFP level 2 years after the operation led us to suspect tumor recurrence; however, diagnostic imaging studies showed no evidence of a recurrence or metastases. The serum AFP levels responded well to chemotherapy with transient decreased levels, but continued to rise until finally, 5 years after the operation, adenocarcinoma cells were detected in the pleural effusion. Thus, careful monitoring of the serum AFP levels at regular intervals could be a useful marker to indicate recurrence of esophageal carcinoma. PMID:11759890
Kobayashi, N; Ohbu, M; Kuroyama, S; Kikuchi, S; Shimao, H; Mitomi, H; Kakita, A
Around 1 % of oral cancers are metastases from distant sites. Tumor metastases to the jaw bones are uncommon and are most likely to arise from primary lung, breast, prostate or kidney tumors. Jaw bone metastases from a primary esophageal adenocarcinoma are especially rare, with only 7 reports published in the literature. Here, we describe a case of a 69 year-old male patient where 7 years elapsed between the diagnosis and successful treatment of a poorly differentiated, stage pT2N0 primary esophageal adenocarcinoma and re-presentation with jaw pain due to a metastatic mandibular deposit. The morphological appearance of the metastasis and immunohistochemical positivity with CK20, CK7 and CDX2 strongly supported an adenocarcinoma of upper gastrointestinal tract origin. This case is of particular interest as there is an unusually long time between the detection of the primary esophageal adenocarcinoma and diagnosis of metastatic disease. The longest period of time we have found for this in the literature is 9 months, although it is also reported that some oral metastases may appear more than 10 years following the primary tumor diagnosis. PMID:23740162
Lawes, Kathryn P; Danford, Martin; Di Palma, Silvana
Trypsin or Tumor associated trypsin (TAT) activation of Protease-activated receptor 2 (PAR-2) promotes tumor cell proliferation in gastrointestinal cancers. The role of the trypsin/PAR-2 network in esophageal adenocarcinoma (EA) development has not yet been investigated. The aim of this study is to investigate the role of trypsin/PAR-2 activation in EA tumorogenesis and therapy. We found that esophageal adenocarcinoma cells (EACs) and Barrett’s Metaplasia (BART) expressed high levels of type 3 extra-pancreatic trypsinogen (PRSS3), a novel type of TAT. Activity of secreted trypsin was detected in cultured media from EA OE19 and OE33 cultures but not from BART culture. Surface PAR-2 expression in BART and EACs was confirmed by both flow cytometry and immunofluorescence. Trypsin induced cell proliferation (? 2 fold; P<0.01) in all tested cell lines at a concentration of 10 nM. Inhibition of PAR-2 activity in EACs via the PAR-2 antagonist ENMD (500 µM), anti-PAR2 antibody SAM-11 (2 µg/ml), or siRNA PAR-2 knockdown, reduced cell proliferation and increased apoptosis by up to 4 fold (P<0.01). Trypsin stimulation led to phosphorylation of ERK1/2, suggesting involvement of MAPK pathway in PAR-2 signal transduction. Inhibition of PAR-2 activation or siRNA PAR-2 knockdown in EACs prior to treatment with 5 FU reduced cell viability of EACs by an additional 30% (P<0.01) compared to chemotherapy alone. Our data suggest that extra-pancreatic trypsinogen 3 is produced by EACs and activates PAR-2 in an autocrine manner. PAR-2 activation increases cancer cell proliferation, and promotes cancer cell survival. Targeting the trypsin activated PAR-2 pathway in conjunction with current chemotherapeutic agents may be a viable therapeutic strategy in EA.
Han, Song; Lee, Constance W.; Trevino, Jose G.; Hughes, Steven J.; Sarosi, George A.
Trypsin or Tumor associated trypsin (TAT) activation of Protease-activated receptor 2 (PAR-2) promotes tumor cell proliferation in gastrointestinal cancers. The role of the trypsin/PAR-2 network in esophageal adenocarcinoma (EA) development has not yet been investigated. The aim of this study is to investigate the role of trypsin/PAR-2 activation in EA tumorogenesis and therapy. We found that esophageal adenocarcinoma cells (EACs) and Barrett's Metaplasia (BART) expressed high levels of type 3 extra-pancreatic trypsinogen (PRSS3), a novel type of TAT. Activity of secreted trypsin was detected in cultured media from EA OE19 and OE33 cultures but not from BART culture. Surface PAR-2 expression in BART and EACs was confirmed by both flow cytometry and immunofluorescence. Trypsin induced cell proliferation (? 2 fold; P<0.01) in all tested cell lines at a concentration of 10 nM. Inhibition of PAR-2 activity in EACs via the PAR-2 antagonist ENMD (500 µM), anti-PAR2 antibody SAM-11 (2 µg/ml), or siRNA PAR-2 knockdown, reduced cell proliferation and increased apoptosis by up to 4 fold (P<0.01). Trypsin stimulation led to phosphorylation of ERK1/2, suggesting involvement of MAPK pathway in PAR-2 signal transduction. Inhibition of PAR-2 activation or siRNA PAR-2 knockdown in EACs prior to treatment with 5 FU reduced cell viability of EACs by an additional 30% (P<0.01) compared to chemotherapy alone. Our data suggest that extra-pancreatic trypsinogen 3 is produced by EACs and activates PAR-2 in an autocrine manner. PAR-2 activation increases cancer cell proliferation, and promotes cancer cell survival. Targeting the trypsin activated PAR-2 pathway in conjunction with current chemotherapeutic agents may be a viable therapeutic strategy in EA. PMID:24146905
Han, Song; Lee, Constance W; Trevino, Jose G; Hughes, Steven J; Sarosi, George A
Esophageal adenocarcinoma is an aggressive malignancy with a poor outcome, and its incidence continues to rise at alarming rates. Current treatment strategies combining chemotherapy, radiation, and surgery are plagued with high rates of recurrence and metastasis. Multiple molecular pathways including the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), v-erb-b2 erythroblastic leukemia viral oncogene homolog (ERBB2), and Aurora kinases’ (AURK) pathways are activated in many esophageal adenocarcinomas. In many cases, these pathways have critical roles in tumor progression. Research on the mechanisms by which these pathways contribute to disease progression has resulted in numerous biologic agents and small molecules with the potential to improve outcome. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been.
Mukherjee, Kaushik; Chakravarthy, A. Bapsi; Goff, Laura W.; El-Rifai, Wael
Esophageal adenocarcinoma is the most common type of esophageal cancer in most Western countries and is an important contributor to overall cancer mortality. Most cases of esophageal adenocarcinoma are believed to arise from Barrett’s esophagus. Esophageal adenocarcinoma occurs more frequently in white men over 50?years old, as well as in people with frequent symptoms of gastroesophageal reflux, in smokers and in people who are obese. Higher consumption of fruit and vegetables, use of non-steroidal anti-inflammatory drugs, and infection with Helicobacter pylori have all been shown to reduce the risk of esophageal adenocarcinoma. Here, we review the epidemiological evidence for the major risk factors of esophageal adenocarcinoma and also discuss perspectives for future research.
Thrift, Aaron P.; Pandeya, Nirmala; Whiteman, David C.
Objective To examine the association between dietary glycemic index (GI), glycemic load (GL), total carbohydrate, sugars, starch, and\\u000a fiber intakes and the risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma.\\u000a \\u000a \\u000a \\u000a Methods In an all-Ireland study, dietary information was collected from patients with esophageal adenocarcinoma (n = 224), long-segment Barrett’s esophagus (n = 220), reflux esophagitis (n = 219), and population-based controls (n = 256). Multiple logistic regression analysis examined
Helen G. Mulholland; Marie M. Cantwell; Lesley A. Anderson; Brian T. Johnston; R. G. Peter Watson; Seamus J. Murphy; Heather R. Ferguson; Jim McGuigan; John V. Reynolds; Harry Comber; Liam J. Murray
Incidence rates for esophageal adenocarcinoma have increased by over 500% during the past few decades without clear reasons. Gastroesophageal reflux disease (GERD), obesity, and smoking have been identified as risk factors, although the demographic distribution of these risk factors is not consistent with the demographic distribution of esophageal adenocarcinoma, which is substantially more common among whites and males than any other demographic groups. Numerous epidemiological studies have suggested associations between dietary factors and the risks of esophageal adenocarcinoma and its precursor, Barrett’s esophagus, though a comprehensive review is lacking. The main aim of the present review is to consider the evidence linking dietary factors with the risks of esophageal adenocarcinoma, Barrett’s esophagus, and the progression from Barrett’s esophagus to esophageal adenocarcinoma. The existing epidemiological evidence is strongest for an inverse relationship between intake of vitamin C, ?-carotene, fruits and vegetables, particularly raw fruits and vegetables and dark-green, leafy and cruciferous vegetables, carbohydrates, fiber and iron and the risk of esophageal adenocarcinoma and Barrett’s esophagus. Patients at higher risk for Barrett’s esophagus and esophageal adenocarcinoma may benefit from increasing their consumption of fruits and vegetables and reducing their intake of red meat and other processed food items. Further research is needed to evaluate the relationship between diet and the progression of Barrett’s esophagus to esophageal adenocarcinoma. Evidence from cohort studies will help determine whether randomized chemoprevention trials are warranted for the primary prevention of Barrett’s esophagus or its progression to cancer.
Kubo, Ai; Corley, Douglas A.; Jensen, Christopher D.; Kaur, Rubinder
BACKGROUND: The objective of this study was to examine outcomes in patients undergoing esophageal resection for adenocarcinoma at our institution during a 20-year period and, in particular, to address temporal trends in long-term survival. METHODS: Out of 470 patients who underwent esophagectomy for malignancy between September 1985 and September 2005, a total number of 175 patients presented with esophageal adenocarcinoma.
I Gockel; FS Sultanov; M Domeyer; U Goenner; Th Junginger
Summary The molecular genetics of Barrett’s Esophagus (BE) and its evolution to esophageal adenocarcinoma (EAC) have been widely studied, however, the molecular mechanism of BE-EAC carcinogenesis has not been completely understood. MicroRNA (miRNA) is now essential to understanding the molecular mechanism of cancer progression. Recent findings include the following: (1) miRNA expression profiles can distinguish between BE and EAC; (2) miR-196a is upregulated in EAC tissues targeting annexin A1, thereby exerting anti-apoptotic effects and contributing to EAC cell survival; miR-196a may also constitute a good biomarker of progression during BE-EAC carcinogenesis; and (3) The miR-106b-25 polycistron is activated by genomic amplification and is involved in esophageal neoplastic progression and proliferation via suppression of two target genes, p21 and Bim.
Determination of the risk of lymph-node metastasis is crucial in making appropriate surgical or endoscopic resection therapeutic decisions. The actual number of patients with esophageal adenocarcinomas and esophagogastric junction adenocarcinomas remains relatively low in Japan; therefore, debate still exists as to whether or not intramucosal esophageal adenocarcinoma has a risk of lymph-node metastasis. We report herein a case of lymph-node metastasis in a surgical resection of an esophageal adenocarcinoma with muscularis mucosae invasion, but no lymphovascular involvement. PMID:23617673
Oda, Ichiro; Yamada, Masayoshi; Yoshinaga, Shigetaka; Tachimori, Yuji; Kushima, Ryoji
Background High expression of Bmi-1, a key regulatory component of the polycomb repressive complex-1, has been associated with many solid and hematologic malignancies including esophageal squamous cell carcinoma. However, little is known about the role of Bmi-1 in esophageal adenocarcinoma. The aim of this study is to investigate the amplification and high expression of Bmi-1 and the associated clinicopathologic characteristics in esophageal adenocarcinoma and squamous cell carcinoma. Methods The protein expression level of Bmi-1 was detected by immunohistochemistry (IHC) from tissue microarrays (TMA) constructed at the University of Rochester from using tissues accrued between 1997 and 2005. Types of tissues included adenocarcinoma, squamous cell carcinoma and precancerous lesions. Patients’ survival data, demographics, histologic diagnoses and tumor staging data were collected. The intensity (0–3) and percentage of Bmi-1 expression on TMA slides were scored by two pathologists. Genomic DNA from 116 esophageal adenocarcinoma was analyzed for copy number aberrations using Affymetrix SNP 6.0 arrays. Fisher exact tests and Kaplan-Meier methods were used to analyze data. Results By IHC, Bmi-1 was focally expressed in the basal layers of almost all esophageal squamous mucosa, which was similar to previous reports in other organs related to stem cells. High Bmi-1 expression significantly increased from squamous epithelium (7%), columnar cell metaplasia (22%), Barrett’s esophagus (22%), to low- (45%) and high-grade dysplasia (43%) and adenocarcinoma (37%). The expression level of Bmi-1 was significantly associated with esophageal adenocarcinoma differentiation. In esophageal adenocarcinoma, Bmi-1 amplification was detected by DNA microarray in a low percentage (3%). However, high Bmi-1 expression did not show an association with overall survival in both esophageal adenocarcinoma and squamous cell carcinoma. Conclusions This study demonstrates that high expression Bmi-1 is associated with esophageal adenocarcinoma and precancerous lesions, which implies that Bmi-1 plays an important role in early carcinogenesis in esophageal adenocarcinoma.
Owing to the rarity of metastatic disease to the bones of the foot, the guidelines for the proper care and workup of such conditions are inconsistent. The present case illustrates the evaluation of a patient with established esophageal adenocarcinoma that metastasized to involve the hallux, which had not been confirmed by previous imaging scans. The purpose of reporting the present case was to aid in establishing a protocol for a multidisciplinary approach to patient care and evaluating the entire body when performing metastatic disease treatment. As the present case has shown, evaluation of various abnormalities such as chronic paronychia could mask additional underlying conditions related to the patient's primary cancer. PMID:22153295
Atway, Said; Vancourt, Robert
Endoscopic therapy for Barrett's esophagus is feasible and likely to decrease the future risk of development of esophageal adenocarcinoma. The most commonly used therapy is radiofrequency ablation, which has been shown to produce reproducible superficial injury in the esophagus. Other thermal therapies include multipolar coagulation, argon plasma coagulation, and thermal laser therapy. The other end of the ablative spectrum includes cryotherapy, which involves freezing tissue to produce mucosal necrosis. Photodynamic therapy has been used to photochemically eliminate abnormal mucosa. Endoscopic therapy has been demonstrated to be effective in high-risk situations such as Barrett's esophagus with high-grade dysplasia. PMID:23452637
Leggett, Cadman L; Gorospe, Emmanuel C; Wang, Kenneth K
Esophageal cancer ranks sixth in cancer death. To explore its genetic origins, we conducted exomic sequencing on 11 esophageal adenocarcinomas (EAC) and 12 esophageal squamous cell carcinomas (ESCC) from the United States. Interestingly, inactivating mutations of NOTCH1 were identified in 21% of ESCCs but not in EACs. There was a substantial disparity in the spectrum of mutations, with more indels in ESCCs, A:T>C:G transversions in EACs, and C:G>G:C transversions in ESCCs (P < 0.0001). Notably, NOTCH1 mutations were more frequent in North American ESCCs (11 of 53 cases) than in ESCCs from China (1 of 48 cases). A parallel analysis found that most mutations in EACs were already present in matched Barrett esophagus. These discoveries highlight key genetic differences between EACs and ESCCs and between American and Chinese ESCCs, and suggest that NOTCH1 is a tumor suppressor gene in the esophagus. Finally, we provide a genetic basis for the evolution of EACs from Barrett esophagus. PMID:22877736
Agrawal, Nishant; Jiao, Yuchen; Bettegowda, Chetan; Hutfless, Susan M; Wang, Yuxuan; David, Stefan; Cheng, Yulan; Twaddell, William S; Latt, Nyan L; Shin, Eun J; Wang, Li-Dong; Wang, Liang; Yang, Wancai; Velculescu, Victor E; Vogelstein, Bert; Papadopoulos, Nickolas; Kinzler, Kenneth W; Meltzer, Stephen J
OBJECTIVE To use a population-based approach to describe survival trends in patients diagnosed as having gastric or esophageal adenocarcinoma. PATIENTS AND METHODS A population-based complete chart review of all inpatient and outpatient records, using the resources of the Rochester Epidemiology Project, was conducted in Olmsted County, Minnesota (population 124,277), a primarily rural county with one large urban area. All residents of Olmsted County who were diagnosed as having gastric or esophageal adenocarcinoma from January 1, 1971, through December 31, 2000, were included in the study. The main outcomes were median survival and 2-year and 5-year survival rates, by decade of diagnosis. RESULTS From 1971 through 2000, median survival for patients with gastric adenocarcinoma (n=121) decreased from 5.5 months to 3.2 months, whereas median survival for patients with esophageal adenocarcinoma (n=65) increased from 8.5 months to 11.7 months. Decade of diagnosis was not significantly associated with patient survival for either gastric or esophageal adenocarcinoma (P>.05). There was no significant shift in stage of disease at diagnosis during the 30-year period for either gastric or esophageal adenocarcinoma (P>.05). CONCLUSION No significant change has occurred in the survival rates of this patient population with gastric or esophageal adenocarcinoma, which is representative of the US white population.
Crane, Sarah J.; Locke, G. Richard; Harmsen, William S.; Zinsmeister, Alan R.; Romero, Yvonne; Talley, Nicholas J.
AIM: To characterise expression of known E-cadherin repressors; Snail , Slug and Twist in the development of esophageal adenocarcinoma. METHODS: E-cadherin , Slug , Snail and Twist mRNA expression in Barrett's metaplasia and esophageal adenocarcinoma specimens was examined by real-time reverse transcription-polymerase chain reaction (RT- PCR). Semi-quantitative immunohistochemistry was used to examine cellular localization and protein levels. The effect of
Paras Jethwa; Mushal Naqvi; Robert G Hardy; Neil A Hotchin; Sally Roberts; Robert Spychal; Chris Tselepis
Aberrant DNA methylation (DNAm) is a feature of most types of cancers. Genome-wide DNAm profiling has been performed successfully on tumor tissue DNA samples. However, the invasive procedure limits the utility of tumor tissue for epidemiological studies. While recent data indicate that cell-free circulating DNAm (cfDNAm) profiles reflect DNAm status in corresponding tumor tissues, no studies have examined the association of cfDNAm with cancer or precursors on a genome-wide scale. The objective of this pilot study was to evaluate the putative significance of genome-wide cfDNAm profiles in esophageal adenocarcinoma (EA) and Barrett esophagus (BE, EA precursor). We performed genome-wide DNAm profiling in EA tissue DNA (n = 8) and matched serum DNA (n = 8), in serum DNA of BE (n = 10), and in healthy controls (n = 10) using the Infinium HumanMethylation27 BeadChip that covers 27,578 CpG loci in 14,495 genes. We found that cfDNAm profiles were highly correlated to DNAm profiles in matched tumor tissue DNA (r = 0.92) in patients with EA. We selected the most differentially methylated loci to perform hierarchical clustering analysis. We found that 911 loci can discriminate perfectly between EA and control samples, 554 loci can separate EA from BE samples, and 46 loci can distinguish BE from control samples. These results suggest that genome-wide cfDNAm profiles are highly consistent with DNAm profiles detected in corresponding tumor tissues. Differential cfDNAm profiling may be a useful approach for the noninvasive screening of EA and EA premalignant lesions.
Zhai, Rihong; Zhao, Yang; Su, Li; Cassidy, Lauren; Liu, Geoffrey; Christiani, David C
TGF-? and Notch signaling pathways play important roles in regulating self-renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-? signaling components activates Notch signaling in esophageal adenocarcinoma, but the basis for this effect has been unclear. Here we report that loss of TGF-? adapter ?2SP (SPNB2) activates Notch signaling and its target SOX9 in primary fibroblasts or esophageal adenocarcinoma cells. Expression of the stem cell marker SOX9 was markedly higher in esophageal adenocarcinoma tumor tissues than normal tissues, and its higher nuclear staining in tumors correlated with poorer survival and lymph node invasion in esophageal adenocarcinoma patients. Downregulation of ?2SP by lentivirus short hairpin RNA increased SOX9 transcription and expression, enhancing nuclear localization for both active Notch1 (intracellular Notch1, ICN1) and SOX9. In contrast, reintroduction into esophageal adenocarcinoma cells of ?2SP and a dominant-negative mutant of the Notch coactivator mastermind-like (dnMAN) decreased SOX9 promoter activity. Tumor sphere formation and invasive capacity in vitro and tumor growth in vivo were increased in ?2SP-silenced esophageal adenocarcinoma cells. Conversely, SOX9 silencing rescued the phenotype of esophageal adenocarcinoma cells with loss of ?2SP. Interaction between Smad3 and ICN1 via Smad3 MH1 domain was also observed, with loss of ?2SP increasing the binding between these proteins, inducing expression of Notch targets SOX9 and C-MYC, and decreasing expression of TGF-? targets p21(CDKN1A), p27 (CDKN1B), and E-cadherin. Taken together, our findings suggest that loss of ?2SP switches TGF-? signaling from tumor suppression to tumor promotion by engaging Notch signaling and activating SOX9.
Song, Shumei; Maru, Dipen M.; Ajani, Jaffer A.; Chan, Chia-Hsin; Honjo, Soichiro; Lin, Hui-Kuan; Correa, Arlene; Hofstetter, Wayne L.; Davila, Marta; Stroehlein, John; Mishra, Lopa
Objective To report a case of esophageal cancer in an adult patient with cystic fibrosis (CF) and review the relationship between these 2 diseases. Case Report A 40-year-old man with CF presented with worsening epigastric pain, weight loss, and upper gastrointestinal (GI) bleeding. Endoscopy revealed innumerable masses in the distal esophagus. The workup revealed esophageal adenocarcinoma metastatic to the liver and the lungs. Discussion Abnormal mucous secretions in CF patients impair the innate GI mucosal barriers. The incidence of both gastroesophageal reflux disease and GI malignancies is higher in patients with CF. Patients with CF now survive long enough to potentially experience the consequences of long-term acid exposure, including esophagitis, Barrett esophagus, and esophageal cancer. Conclusion Our case report adds to a small but growing body of evidence that CF is a significant risk factor for GI malignancies, including esophageal adenocarcinoma. Controlled studies are needed to determine whether a causal relationship truly exists.
Holt, Edward W.; Yimam, Kidist K.; Liberman, Martin S.
High intake of phytoestrogen lignans has been found to be associated with decreased risk of esophageal adenocarcinoma in our previous population-based case-control study in Sweden. To further evaluate this possible association, we tested the hypothesis of an inverse association between dietary lignan intake and risk of esophageal and gastric adenocarcinoma using a prospective design. In a population-based cohort study in Sweden, 81,670 participants who were cancer-free at baseline were followed up during 1998 to 2009. All participants completed a 96-item food frequency questionnaire (FFQ), which was used to assess dietary exposure to lignans (secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol, and syringaresinol). All cases of esophageal, gastroesophageal junctional, and gastric adenocarcinoma were identified through linkage to the Swedish Cancer Register. Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CI), with adjustment for potential confounding factors. During an average follow-up of 9.9 years, a total of 211 cases were identified, including 83 cases of esophageal or junctional adenocarcinoma, and 128 cases of gastric adenocarcinoma. There was no statistically significant association between dietary intake of lignans and any of the studied adenocarcinomas. Compared with participants in the lowest quartile of lignan intake, the adjusted HR of the highest quartile was 0.96 (95% CI, 0.46-2.00; P(trend) = 0.70) for adenocarcinoma of the esophagus or gastroesophageal junction, and 0.89 (95% CI, 0.52-1.55: P(trend) = 0.78) for gastric adenocarcinoma. No clear support for a protective role of dietary intake of lignans in the development of esophageal or gastric adenocarcinoma was found. PMID:23195991
Lin, Yulan; Wolk, Alicja; Hĺkansson, Niclas; Lagergren, Jesper; Lu, Yunxia
Esophageal cancer (EC) ranks sixth in cancer death. To explore its genetic origins, we performed exomic sequencing on 11 adenocarcinomas (EAC) and 12 squamous cell carcinomas (ESCCs) from the United States. Interestingly, inactivating mutations of NOTCH1 were identified in 21% of ESCCs but not in EACs. There was a substantial disparity in the spectrum of mutations, with more indels in ESCCs, A:T>C:G transversions in EACs, and C:G>G:C transversions in ESCCs (p<0.0001). Notably, NOTCH1 mutations were more frequent in North American ESCCs (11 of 53 cases) than in ESCCs from China (1 of 48 cases). A parallel analysis found that most mutations in EACs were already present in matched Barrett’s esophagus (BE). These discoveries highlight key genetic differences between EAC and ESCC, American and Chinese ESCC, and suggest that NOTCH1 is a tumor suppressor gene in the esophagus. Finally, we provide a genetic basis for the evolution of EACs from BE.
Agrawal, Nishant; Jiao, Yuchen; Bettegowda, Chetan; Hutfless, Susan M.; Wang, Yuxuan; David, Stefan; Cheng, Yulan; Twaddell, William S.; Latt, Nyan L.; Shin, Eun J.; Wang, Li-Dong; Wang, Liang; Yang, Wancai; Velculescu, Victor E.; Vogelstein, Bert; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Meltzer, Stephen J.
Development from chronic inflammation to Barrett's adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett's epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett's adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing.
Fujimura, Takashi; Oyama, Katsunobu; Sasaki, Shozo; Nishijima, Koji; Miyashita, Tomoharu; Ohta, Tetsuo; Koichi, Miwa; Takanori, Hattori
The overexpression of AXL receptor tyrosine kinase is a frequent finding that has been associated with poor prognosis in esophageal adenocarcinoma (EAC). As the majority of EAC are intrinsically resistant to DNA-damaging therapies, an alternative therapeutic approach based on the activation of death receptors may be warranted. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been evaluated in clinical trials and found promising as anticancer agent with mild side effects; unfortunately, resistance to TRAIL remains a major clinical problem. Herein, we explored the role of AXL in TRAIL resistance and elucidated the underlying mechanism. Overexpression of AXL in OE33 and OE19 cells promoted cell survival and attenuated TRAIL-induced cellular and molecular markers of apoptosis. In contrast, knockdown of endogenous AXL sensitized FLO-1 cells to TRAIL. The mechanism by which AXL regulates TRAIL resistance was examined. Protein and mRNA expression of DR4 and DR5 death receptors was not downregulated by AXL. In addition, the possible involvement of FLICE-inhibitory protein (FLIP) in regulating the interaction of caspase-8 with Fas-associated death domain protein (FADD) was excluded, as AXL did not enhance FLIP expression or FLIP/FADD association. Alternatively, protein association of AXL with DR5, independent of TRAIL, was confirmed, suggesting that AXL could regulate DR5 receptor activity. The AXL/DR5 association had no negative effect on TRAIL-induced interaction with FADD. However, the AXL/DR5 interaction blocked the recruitment of caspase-8 to the death-inducing signal complex (DISC). Collectively, our findings uncover a novel mechanism of TRAIL resistance mediated by AXL through regulation of the DISC and provide strong evidence that AXL could be exploited as a therapeutic target to circumvent TRAIL resistance.
Hong, Jun; Belkhiri, Abbes
BackgroundDespite many attempts to establish pre-treatment prognostic markers to understand the clinical biology of esophageal adenocarcinoma (EAC), validated clinical biomarkers or parameters remain elusive. We generated and analyzed tumor transcriptome to develop a practical biomarker prognostic signature in EAC.Methodology\\/Principal FindingsUntreated esophageal endoscopic biopsy specimens were obtained from 64 patients undergoing surgery and chemoradiation. Using DNA microarray technology, genome-wide gene expression
Soo Mi Kim; Yun-Yong Park; Eun Sung Park; Jae Yong Cho; Julie G. Izzo; Di Zhang; Sang-Bae Kim; Jeffrey H. Lee; Manoop S. Bhutani; Stephen G. Swisher; Xifeng Wu; Kevin R. Coombes; Dipen Maru; Kenneth K. Wang; Navtej S. Buttar; Jaffer A. Ajani; Ju-Seog Lee; Patrick Tan
Overexpression of FGF-2 is associated with tumor recurrence and reduced survival after surgical resection of esophageal cancer,\\u000a and these risks are reduced in tumors co-expressing the FGF antisense (FGF-AS) RNA. The aim of this study was to characterize\\u000a the expression of alternatively spliced FGF-AS transcripts and encoded nudix-motif proteins in normal human tissues and in\\u000a esophageal adenocarcinoma, and to correlate
Shuo Cheng Zhang; Christie Barclay; Leigh Ann Alexander; Laurette Geldenhuys; Geoffrey A. Porter; Alan G. Casson; Paul R. Murphy
This paper presents commentaries on animal models used for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) research; acid- and bile-induced chromosomal instability and clonal selection during the progression of BE to EAC; how the components of gastric refluxate, especially acid and bile salts, promote carcinogenesis in metaplastic BE; genome-wide changes in DNA methylation and transcription involved in BE carcinogenesis; the potential role of miRNA in the development of BE and EAC; the effect of inflammatory cytokines linked to obesity on the activation of cell-death pathways and cell survival in BE and esophageal cancer; and the role of autophagy in esophageal cancer development. PMID:24117642
Fang, Yu; Chen, Xiaoxin; Bajpai, Manisha; Verma, Amit; Das, Kiron M; Souza, Rhonda F; Garman, Katherine S; Donohoe, Claire L; O'Farrell, Naoimh J; Reynolds, John V; Dvorak, Katerina
ObjectiveThe incidence and consequence of an isolated involved circumferential radial margin (CRM) after resection for esophageal adenocarcinoma in the setting of neoadjuvant chemoradiation (CRT) has not been reported. We aim to determine the frequency and significance of a close (
John A. Harvin; Guy Lahat; Arlene M. Correa; Jared Lee; Dipen Maru; Jaffer Ajani; Edith M. Marom; James Welsh; Manoop S. Bhutani; Garret Walsh; Jack Roth; Reza Mehran; Ara Vaporciyan; David Rice; Stephen Swisher; Wayne Hofstetter
BACKGROUND: Barrett's esophagus (BE) is the metaplastic replacement of squamous with columnar epithelium in the esophagus, as a result of reflux. It is the major risk factor for the development of esophageal adenocarcinoma (EAC). Methylation of CpG dinucleotides of normally unmethylated genes is associated with silencing of their expression, and is common in EAC. This study was designed to determine
Eric Smith; Neville J De Young; Sandra J Pavey; Nicholas K Hayward; Derek J Nancarrow; David C Whiteman; B Mark Smithers; Andrew R Ruszkiewicz; Andrew D Clouston; David C Gotley; Peter G Devitt; Glyn G Jamieson; Paul A Drew
The prevalence of esophageal adenocarcinoma in the setting of Barrett's metaplasia continues to increase in Western nations at a rate greater than any other cancer. The trophic properties of gastrin have been documented in gastric, pancreatic and colon cancer cell lines, suggesting a potential role for this regulatory peptide in the growth of these malignancies. The aims of these studies were to identify and characterize the presence of functional cholecystokinin type-2 (gastrin) receptors on the membranes of human esophageal adenocarcinoma cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated the presence of cholecystokinin type-2 receptor transcripts in human esophageal adenocarcinoma cell lines. Competitive binding assays revealed specific binding of gastrin in SEG-1 cells (IC50 of 2.4 x 10(-8) M). This finding was confirmed by laser scanning confocal microscopy through internalization of rhodamine green labeled gastrin heptapeptide in SEG-1 cells. Gastrin caused a dose-dependent increase in proliferation of SEG-1 cells when compared to controls. This effect was abolished by co-incubation with L365,260, a CCK-2-specific receptor antagonist. Gastrin-induced phosphorylation of the p44 and p42 mitogen-activated protein kinases was demonstrated by Western blot analysis. In conclusion, the studied human esophageal adenocarcinoma cell lines possess cholecystokinin type-2 (gastrin) receptors. Receptors bind gastrin, resulting in increased proliferation in SEG-1 cells. PMID:15177938
Moore, T Carlton; Jepeal, Lisa I; Boylan, Michael O; Singh, Satish K; Boyd, Nick; Beer, David G; Chang, Albert J; Wolfe, M Michael
The prevalence of esophageal adenocarcinoma in the setting of Barrett's metaplasia continues to increase in Western nations at a rate greater than any other cancer. The trophic properties of gastrin have been documented in gastric, pancreatic and colon cancer cell lines, suggesting a potential role for this regulatory peptide in the growth of these malignancies. The aims of these studies
T. Carlton Moore; Lisa I. Jepeal; Michael O. Boylan; Satish K. Singh; Nick Boyd; David G. Beer; Albert J. Chang; M. Michael Wolfe
The Hedgehog (Hh) pathway is known to be active in Barrett's carcinogenesis. Therefore, we evaluated the efficacy and underlying mechanisms of inhibition of cancer cell growth by the smoothened (Smo) antagonist BMS-833923 in esophageal adenocarcinoma (EAC) cell lines. Cell proliferation and apoptosis were evaluated by flow cytometry, Western blotting, immunofluorescence, and quantitative reverse transcription polymerase chain reactions. Results showed that the Smo antagonist led to reduced Hh pathway activity, resulting in decreased cell proliferation and induction of apoptosis via the intrinsic pathway in the esophageal cancer cells. In conclusion, the Smo antagonist may have application as an EAC chemotherapeutic agent. PMID:23915072
Zaidi, Ali H; Komatsu, Yoshihiro; Kelly, Lori A; Malhotra, Usha; Rotoloni, Christina; Kosovec, Juliann E; Zahoor, Haris; Makielski, Rory; Bhatt, Astha; Hoppo, Toshitaka; Jobe, Blair A
In order to establish an animal model for studying the cause and prevention of esophageal adenocarcinoma (EAC) and its frequent precursor, Barrett's esophagus (BE), fac- tors affecting the pathogenic processes were investigated in an esophagoduodenal anastomosis model with rats. Experiments by us and others have shown that surgical treatment produced reflux esophagitis with cell hyperprolif- eration, but not EAC. Additional
Susan R. Goldstein; Guang-yu Yang; Stephen K. Curtis; Kenneth R. Reuhl; Bao-Chi Liu; Sidney S. Mirvish; Harold L. Newmark; Chung S. Yang
Purpose Apoptosis pathway, gastroesophageal reflux symptoms (reflux), higher body mass index (BMI), and tobacco smoking have been individually associated with esophageal adenocarcinoma (EA) development. However, how multiple factors jointly affect EA risk remains unclear. Patients and Methods In total, 305 patients with EA and 339 age- and sex-matched controls were studied. High-order interactions among reflux, BMI, smoking, and functional polymorphisms in five apoptotic genes (FAS, FASL, IL1B, TP53BP, and BAT3) were investigated by entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional logistic regression (LR) models. Results In LR analysis, reflux, BMI, and smoking were significantly associated with EA risk, with reflux as the strongest individual factor. No individual single nucleotide polymorphism was associated with EA susceptibility. However, there was a two-way interaction between IL1B + 3954C>T and reflux (P = .008). In both CART and MDR analyses, reflux was also the strongest individual factor for EA risk. In individuals with reflux symptoms, CART analysis indicated that strongest interaction was among variant genotypes of IL1B + 3954C>T and BAT3S625P, higher BMI, and smoking (odds ratio [OR], 5.76; 95% CI, 2.48 to13.38), a finding independently found using MDR analysis. In contrast, for participants without reflux symptoms, the strongest interaction was found between higher BMI and smoking (OR, 3.27; 95% CI, 1.88 to 5.68), also echoed by entropy-based MDR analysis. Conclusion Although a history of reflux is an important risk for EA, multifactor interactions also play important roles in EA risk. Gene-environment interaction patterns differ between patients with and without reflux symptoms.
Zhai, Rihong; Chen, Feng; Liu, Geoffrey; Su, Li; Kulke, Matthew H.; Asomaning, Kofi; Lin, Xihong; Heist, Rebecca S.; Nishioka, Norman S.; Sheu, Chau-Chyun; Wain, John C.; Christiani, David C.
OBJECTIVES:The extent of reduction of esophageal adenocarcinoma (EAC) incidence in Barrett's esophagus (BE) patients after endoscopic ablation is not known. The objective of this study was to determine the cancer incidence in BE patients after ablative therapy and compare these rates to cohort studies of BE patients not undergoing ablation.METHODS:A MEDLINE search of the literature on the natural history and
Sachin Wani; Srinivas R Puli; Nicholas J Shaheen; Brenda Westhoff; Sanjeev Slehria; Ajay Bansal; Amit Rastogi; Hari Sayana; Prateek Sharma
We report clonal chromosome abnormalities in short term cultures of seven gastric or esophageal adenocarcinomas and two squamous carcinomas of the esophagus and EG junction. The most consistent aberration encountered was a del(3)(q13.2q23) seen in six of nine tumors. This finding, together with a survey of published cytogenetic literature, suggested that del(3q) is the most common cytogenetic abnormality, and hence
Pulivarthi H. Rao; Susan Mathew; David P. Kelsen; R. S. K. Chaganti
Background: Esophageal adenocarcinoma (EAC) is increas- ing at the most rapid rate of any cancer in the United States. An esophagogastroduodenal anastomosis (EGDA) surgical model in rats mimics human gastroesophageal reflux and results in EAC. Leukotriene A4 hydrolase (LTA4H), a pro- tein overexpressed in EAC in this model, is a rate-limiting enzyme in the biosynthesis of leukotriene B4 (LTB4), a
Xiaoxin Chen; Ning Li; Su Wang; Nan Wu; Jungil Hong; Xiaolong Jiao; Mark J. Krasna; David G. Beer; Chung S. Yang
Gene amplification is a tumor-specific event during malignant transformation. Recent studies have proposed a lineage-dependency (addiction) model of human cancer whereby amplification of certain lineage transcription factors predisposes a survival mechanism in tumor cells. These tumor cells are derived from tissues where the lineage factors play essential developmental and maintenance roles. Here, we show that recurrent amplification at 18q11.2 occurs in 21% of esophageal adenocarcinomas (EAC). Utilization of an integrative genomic strategy reveals a single gene, the embryonic endoderm transcription factor GATA6, as the selected target of the amplification. Overexpression of GATA6 is found in EACs that contain gene amplification. We find that EAC patients whose tumors carry GATA6 amplification have a poorer survival. We show that ectopic expression of GATA6, together with FGFR2 isoform IIIb, increases anchorage-independent growth in immortalized Barrett's esophageal cells. Conversely, siRNA-mediated silencing of GATA6 significantly reduces both cell proliferation and anchorage-independent growth in EAC cells. We further demonstrate that induction of apoptotic/anoikis pathways is triggered upon silencing of GATA6 in EAC cells but not in esophageal squamous cells. We show that activation of p38? signaling and up-regulation of TNF-related apoptosis-inducing ligand are detected in apoptotic EAC cells upon GATA6 deprivation. We conclude that selective gene amplification of GATA6 during EAC development sustains oncogenic lineage-survival of esophageal adenocarcinoma. PMID:22375031
Lin, Lin; Bass, Adam J; Lockwood, William W; Wang, Zhuwen; Silvers, Amy L; Thomas, Dafydd G; Chang, Andrew C; Lin, Jules; Orringer, Mark B; Li, Weiquan; Glover, Thomas W; Giordano, Thomas J; Lam, Wan L; Meyerson, Matthew; Beer, David G
Purpose Esophageal cancer is one of the most aggressive and deadly forms of cancer; highlighting the need to identify biomarkers for early detection and prognostic classification. Our recent studies have identified inflammatory gene and microRNA signatures derived from tumor and nontumor tissues as prognostic biomarkers of hepatocellular, lung, and colorectal adenocarcinoma. Here, we examine the relationship between expression of these inflammatory genes and miRNA expression in esophageal adenocarcinoma and patient survival. Experimental Design We measured the expression of 23 inflammation-associated genes in tumors and adjacent normal tissues from 93 patients (58 Barrett's and 35 Sporadic adenocarcinomas) by quantitative reverse transcription-polymerase chain reaction. These data were used to build an inflammatory risk model, based on multivariate Cox regression, to predict survival in a training cohort (n=47). We then determined if this model could predict survival in a cohort of 46 patients. Expression data for miRNA-375 was available for these patients and was combined with inflammatory gene expression. Results IFN?, IL-1?, IL-8, IL-21, IL-23, and PRG expression in tumor and nontumor samples were each associated with poor prognosis based on Cox regression ([Z-score]>1.5) and therefore, were used to generate an inflammatory risk score (IRS). Patients with a high IRS had poor prognosis compared to those with a low IRS in the training (P=0.002) and test (P=0.012) cohorts. This association was stronger in the group with Barrett's history. When combining with miRNA-375, the combined IRS/miR signature was an improved prognostic classifier than either one alone. Conclusion Transcriptional profiling of inflammation-associated genes and miRNA expression in resected esophageal Barrett's associated adenocarcinoma tissues may have clinical utility as predictors of prognosis.
Nguyen, Giang Huong; Schetter, Aaron J.; Chou, David B.; Bowman, Elise D.; Zhao, Ronghua; Hawkes, Jason E.; Mathe, Ewy A.; Kumamoto, Kensuke; Zhao, Yiqiang; Budhu, Anuradha; Hagiwara, Nobutoshi; Wang, Xin Wei; Miyashita, Masao; Casson, Alan G.; Harris, Curtis C.
The objective of this exploratory study was to evaluate the feasibility of using Fourier-Transform Infrared (FTIR) spectromicroscopy to characterize formalin-fixed, paraffin-embedded human esophageal tissues. Matched histologically normal esophageal squamous epithelium (NS), premalignant Barrett esophagus (BE), and primary esophageal adenocarcinoma (EADC) tissues, each defined according to strict clinicopathologic criteria, were obtained from patients who underwent esophageal resection. Using confocal IR microscopy, measurements in the mid-IR spectral region were carried out in transflection configuration, scanning regions of interest in 15 microm steps. A multidimensional dataset reporting the spectroscopic properties at each sampled point were analyzed by performing a hierarchical cluster analysis on the second derivative of spectral traces. Normal esophageal epithelia were characterized by a few well defined regions, mostly of large size (tens of contiguous pixels), which correlated with tissue histology, specifically the basal cell layer. BE tissues had characteristic regions localized to gland crypts, ranging in size from one pixel to a few tens of pixels, which displayed IR spectra with defined absorption features characteristic of glycoproteins. The incorporation of synchrotron light to improve the resolution of individual cells in BE tissues has demonstrated that these glycoproteins are associated with goblet cells, the characteristic cell type defining BE. Whereas the highly fragmented regions identified in EADC likely reflect tumor heterogeneity, FTIR mapping would appear to be a potentially useful technique to identify premalignant BE tissues. The technical feasibility of using FTIR to characterize formalin-fixed, paraffin-embedded human esophageal tissues demonstrates the potential of this technique to study archival human BE tissue specimens via automated screening techniques. PMID:19475154
Quaroni, Luca; Casson, Alan G
Gastroesophageal reflux disease complicated by Barrett’s esophagus (BE) is a major risk factor for esophageal adenocarcinoma (EA). However, the mechanisms of the progression from BE to EA are not fully understood. Besides acid reflux, bile acid reflux may also play an important role in the progression from BE to EA. In this study we examined the role of phosphatidylinositol-specific phospholipase C (PI-PLC) and a novel NADPH oxidase NOX5-S in bile acid-induced in cell proliferation. We found that taurodeoxycholic acid (TDCA) significantly increased NOX5-S expression, H2O2 production and cell proliferation in EA cells. The TDCA-induced increase in cell proliferation was significantly reduced by U73122, an inhibiter of PI-PLC. PI-PLC?1, ?3, ?4, ?1 and ?2, but not ?2 and ?1 were detectable in FLO cells by Western blot analysis. Knockdown of PI-PLC?2 or ERK-2 MAP kinase with siRNAs significantly decreased TDCA-induced increase in NOX5-S expression, H2O2 production and cell proliferation. In contrast, knockdown of PI-PLC ?1, ?3, ?4, ?1 or ERK-1 MAP kinase had no significant effect. TDCA significantly increased ERK-2 phosphorylation, an increase which was reduced by U73122 or PI-PLC?2 siRNA. We conclude that TDCA-induced increase in NOX5-S expression and cell proliferation may depend on sequential activation of PI-PLC?2 and ERK-2 MAP kinase in EA cells. It is possible that bile acid reflux present in patients with Barrett’s esophagus may increase ROS production and cell proliferation via activation of PI-PLC?2, ERK-2 MAP kinase and NADPH oxidase NOX5-S, thereby contributing to the development of EA.
Hong, Jie; Behar, Jose; Wands, Jack; Resnick, Murray; Wang, Li Juan; DeLellis, Ronald A.; Lambeth, David; Cao, Weibiao
OBJECTIVES:To describe the incidence trends in esophageal squamous cell carcinoma (SCC) and adenocarcinoma among the three major ethnic groups in Singapore from 1968 to 2002.METHODS:Esophageal cancer cases in Singapore citizens and permanent residents obtained from the Singapore Cancer Registry and population data derived from the national census were used to calculate the incidence rates from 1968 to 2002.RESULTS:The age-standardized incidence
Mark L. Fernandes; Adeline Seow; Yiong-Huak Chan; Khek-Yu Ho
Excess body weight (body mass index >25 kg/m(2)) is common in patients with esophageal adenocarcinoma. In this study, a meta-analysis was performed by searching PubMed, Cochrane Library, EMBASE, and Science Direct databases from 1960 to June 2012. Data were extracted from studies comparing survival in obese (body mass index >30), overweight (body mass index 25-29), and normal-weight (body mass index 20-24) patients undergoing esophagectomy. A total of six studies with 1988 cases were suitable for this global meta-analysis. Compared with patients of normal weight, the hazard ratio of postoperational survival for overweight and obese patients was 0.79 (95% confidence interval 0.65-0.95, P = 0.108) and 0.80 (95% confidence interval 0.68-0.93, P = 1.00), respectably. Taken together, the excess body weight did not have the value of predicting survival for patients with esophageal adenocarcinoma. PMID:23317016
Hong, L; Zhang, H; Zhao, Q; Han, Y; Yang, J; Brain, L
p53 alterations have been implicated in the progression of Barrett's esophagus to esophageal adenocarcinoma. However, the wide range of reported p53 alteration frequencies in esophageal adenocarcinoma makes using p53 as a marker of malignant transformation of Barrett's esophagus problematic. To determine the utility of p53 in Barrett's esophagus monitoring, the frequency of p53 alteration was critically reassessed using esophagectomy specimens of 40 cases of esophageal adenocarcinoma, including 10 with Barrett's esophagus and high-grade dysplasia, 8 with low-grade dysplasia and 7 with no dysplasia. DNA was extracted from tumor cells isolated by laser capture microdissection to maximize the assay sensitivity and mutations in exons 4-8 of p53 were determined by PCR direct sequencing. Mutations in p53 were identified in 75% (30/40) of the esophageal adenocarcinoma. p53 protein overexpression, detected by immunohistochemistry, was found in 58% (23/40) of the esophageal adenocarcinoma, 60% (6/10) of Barrett's esophagus with high-grade dysplasia, 12% (1/8) of Barrett's esophagus with low-grade dysplasia, and 0% of Barrett's esophagus without dysplasia. In addition to the mutations, a predominance of the 72Arg allele (89% homozygous) was found over the 72Pro allele in this series. p53 mutation frequency in this study was higher than reported in most of the literature and DNA sequencing detected more p53 alterations than immunohistochemical staining. However, p53 appeared to be a late marker in the neoplastic transformation, and no p53 change was found in approximately 25% of the adenocarcinoma. We concluded that p53 is insufficient as a single marker for Barrett's esophagus monitoring but may be useful as part of a panel due to its high specificity. PMID:17982662
Chung, Sun M; Kao, Jean; Hyjek, Elizabeth; Chen, Yao-Tseng
AIM: To determine the effects of duodenogastric juice pH on the development of esophageal adenocarcinoma (EAC). METHODS: An animal model of duodenogastroesophageal reflux was established using Sprague-Dawley (SD) rats undergoing esophagoduodenostomy (ED). The development of EAC was investigated in rats exposed to duodenogastric juice of different pH. The rats were divided into three groups: low-pH group (group A), high-pH group (group B) and a sham-operated group as a control (group C) (n = 30 rats in each group). The incidence of esophagitis, Barrett’s esophagus (BE), intestinal metaplasia with dysplasia and EAC was observed 40 wk after the treatment. RESULTS: The incidence rate of esophagitis, BE, intestinal metaplasia with dysplasia and EAC was higher in groups A and B compared with the control group after 40 wk (P < 0.01), being 96% and 100% (P > 0.05), 88% and 82.4% (P > 0.05), 20% and 52.1% (P < 0.05), and 8% and 39% (P < 0.05), respectively. CONCLUSION: Non-acidic refluxate increases the occurrence of intestinal metaplasia with dysplasia and EAC while the low-pH gastric juice exerts a protective effect in the presence of duodenal juice. The non-acid reflux is particularly important in the progression from BE to cancer. Therefore, control of duodenal reflux may be an important prophylaxis for EAC.
Cheng, Peng; Li, Jian-Sheng; Gong, Jun; Zhang, Lian-Feng; Chen, Rong-Zhong
The mechanisms of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not known. Cycloxygenase-2 (COX-2)-derived prostaglandin E? (PGE?) has been shown to be important in esophageal tumorigenesis. We have shown that COX-2 mediates acid-induced PGE? production. The prostaglandin E synthase (PGES) responsible for acid-induced PGE2 production in BE, however, is not known. We found that microsomal PGES1 (mPGES1), mPGES2, and cytosolic PGES (cPGES) were present in FLO EA cells. Pulsed acid treatment significantly increased mPGES1 mRNA and protein levels but had little or no effect on mPGES2 or cPGES mRNA. Knockdown of mPGES1 by mPGES1 small interfering RNA (siRNA) blocked acid-induced increase in PGE2 production and thymidine incorporation. Knockdown of NADPH oxidase, NOX5-S, a variant lacking calcium-binding domains, by NOX5 siRNA significantly inhibited acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Overexpression of NOX5-S significantly increased the luciferase activity in FLO cells transfected with a nuclear factor ?B (NF-?B) in vivo activation reporter plasmid pNF-?B-Luc. Knockdown of NF-?B1 p50 by p50 siRNA significantly decreased acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE? production. Two novel NF-?B binding elements, GGAGTCTCCC and CGGGACACCC, were identified in the mPGES1 gene promoter. We conclude that mPGES1 mediates acid-induced increase in PGE? production and cell proliferation. Acid-induced mPGES1 expression depends on activation of NOX5-S and NF-?B1 p50. Microsomal PGES1 may be a potential target to prevent or treat EA. PMID:23439561
Zhou, Xiaoxu; Li, Dan; Resnick, Murray B; Wands, Jack; Cao, Weibiao
It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations (AVF) by magnifying endoscopy with narrow-band imaging (ME-NBI), and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontal cross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 ?m from the surface and disappeared at a depth of approximately 300 ?m. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 ?m underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected. PMID:23617670
Omae, Masami; Fujisaki, Junko; Shimizu, Tomoki; Igarashi, Masahiro; Yamamoto, Noriko
A 40-year-old man was referred to our hospital for detailed examination of a protuberant lesion in long-segment Barrett's esophagus (LSBE). Under white light endoscopy (WLE) the lesion appeared as a protuberant lesion with a rough surface and was diagnosed as 0-IIa-type tumor suspected to be a well-differentiated adenocarcinoma. A regular villous pattern was shown in the background mucosa of the LSBE by narrow-band imaging (NBI) magnifying endoscopy (NBI-ME). However, a slightly irregular villous pattern was observed on the lateral side of the main lesion. Therefore, a 0-IIa-type tumor was estimated to have a flatly lateral extension component (i.e. 0-IIb spreading). The 0-IIb spreading was unclear when using WLE, but could be diagnosed by NBI-ME based on the surface pattern differences. Markings were placed outside the edge of the flatly lateral extension, and endoscopic submucosal dissection was carried out.The pathological diagnosis of the protuberant lesion with flatly lateral spreading was well-differentiated adenocarcinoma. The macroscopic type was 0-IIa+IIb, 45 × 43 mm in size. The invasion depth was T1a (deep muscularis mucosae). Lymphatic and venous invasions were negative; horizontal and vertical margins were negative. In conclusion, NBI-ME was useful for the diagnosis of the flatly lateral extension of this 0-IIa+IIb esophageal adenocarcinoma in Barrett's esophagus. Further investigations with many cases are necessary. PMID:23617675
Takahashi, Akiko; Oyama, Tsuneo
Synopsis This articles reviews the environmental risk factors and predisposing conditions for the two main histological types of esophageal cancer, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). Tobacco smoking, excessive alcohol consumption, drinking maté, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of ESCC. Results of investigations on several other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are also discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and probably absence of H. pylori in the stomach increase the risk of EA. Results of studies investigating other factors, including low intake of fresh fruits and vegetables, consumption of carbonated soft drink, use of H2 blockers, non-steroidal anti-inflammatory drugs, and drugs that relax the lower esophageal sphincter are also discussed.
Kamangar, Farin; Chow, Wong-Ho; Abnet, Christian; Dawsey, Sanford
Esophageal adenocarcinoma is a major cause of cancer death in men in the developed world. Continuing poor outcomes with conventional therapies that predominantly target apoptosis pathways have lead to increasing interest in treatments that target the cell cycle. A large international effort has led to the development of a large number of inhibitors, which target cell cycle kinases, including cyclin-dependent kinases, Aurora kinases and polo-like kinase. Initial phase?I/II trials in solid tumors have often demonstrated only modest clinical benefits of monotherapy. This may relate in part to a failure to identify the patient populations that will gain the most clinical benefit. Newer compounds lacking the side effect profile of first-generation compounds may show utility as adjunctive treatments targeted to an individual’s predicted response to treatment.
Dibb, Martyn; Ang, Yeng S
We report analysis of N-glycans derived from disease-free individuals and patients with Barrett's esophagus, high-grade dysplasia, and esophageal adenocarcinoma by microchip electrophoresis with laser-induced fluorescence detection. Serum samples in 10-?L aliquots are enzymatically treated to cleave the N-glycans that are subsequently reacted with 8-aminopyrene-1,3,6-trisulfonic acid to add charge and a fluorescent label. Separations at 1250 V/cm and over 22 cm yielded efficiencies up to 700,000 plates for the N-glycans and analysis times under 100 s. Principal component analysis (PCA) and analysis of variance (ANOVA) tests of the peak areas and migration times are used to evaluate N-glycan profiles from native and desialylated samples and to determine differences among the four sample groups. With microchip electrophoresis, we are able to distinguish the three patient groups from each other and from disease-free individuals.
Mitra, Indranil; Zhuang, Zexi; Zhang, Yuening; Yu, Chuan-Yih; Hammoud, Zane T.; Tang, Haixu; Mechref, Yehia; Jacobson, Stephen C.
For decades, hundreds of different human tumor type–specific cell lines have been used in experimental cancer research as models for their respective tumors. The veracity of experimental results for a specific tumor type relies on the correct derivation of the cell line. In a worldwide effort, we verified the authenticity of all available esophageal adenocarcinoma (EAC) cell lines. We proved that the frequently used cell lines SEG-1 and BIC-1 and the SK-GT-5 cell line are in fact cell lines from other tumor types. Experimental results based on these contaminated cell lines have led to ongoing clinical trials recruiting EAC patients, to more than 100 scientific publications, and to at least three National Institutes of Health cancer research grants and 11 US patents, which emphasizes the importance of our findings. Widespread use of contaminated cell lines threatens the development of treatment strategies for EAC.
Boonstra, Jurjen J.; van Marion, Ronald; Beer, David G.; Lin, Lin; Chaves, Paula; Ribeiro, Catarina; Pereira, A. Dias; Roque, Lucia; Darnton, S. Jane; Altorki, Nasser K.; Schrump, David S.; Klimstra, David S.; Tang, Laura H.; Eshleman, James R.; Alvarez, Hector; Shimada, Yutaka; van Dekken, Herman; Tilanus, Hugo W.
Background Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. Case presentation A 56?year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4?months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. Conclusion We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.
Esophageal adenocarcinomas are poorly responsive to chemotherapeutics. This study aimed to determine the levels of Aurora kinase A (AURKA) and the therapeutic potential of MLN8237, an investigational AURKA inhibitor, alone and in combination with cisplatin. Using quantitative real-time PCR, we detected frequent AURKA gene amplification (15 of 34, 44%) and mRNA overexpression (37 of 44, 84%) in esophageal adenocarcinomas (P < 0.01). Immunohistochemical analysis showed overexpression of AURKA in more than two-thirds of esophageal adenocarcinoma tissue samples (92 of 132, 70%; P < 0.001). Using FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, with constitutive AURKA overexpression and mutant p53, we observed inhibition of colony formation with a single treatment of 0.5 ?mol/L MLN8237 (P < 0.05). This effect was further enhanced in combination with 2.5 ?mol/L cisplatin (P < 0.001). Twenty-four hours after treatment with the MLN8237 or MLN8237 and cisplatin, cell-cycle analyses showed a sharp increase in the percentage of polyploid cells (P < 0.001). This was followed by an increase in the percentage of cells in the sub-G(1) phase at 72 hours, concordant with the occurrence of cell death (P < 0.001). Western blot analysis showed higher induction of TAp73?, PUMA, NOXA, cleaved caspase-3, and cleaved PARP with the combined treatment, as compared with a single-agent treatment. Using xenograft models, we showed an enhanced antitumor role for the MLN8237 and cisplatin combination, as compared with single-agent treatments (P < 0.001). In conclusion, this study shows frequent overexpression of AURKA and suggests that MLN8237 could be an effective antitumor agent, which can be combined with cisplatin for a better therapeutic outcome in esophageal adenocarcinomas. PMID:22302096
Sehdev, Vikas; Peng, DunFa; Soutto, Mohammed; Washington, M Kay; Revetta, Frank; Ecsedy, Jeffrey; Zaika, Alexander; Rau, Tilman T; Schneider-Stock, Regine; Belkhiri, Abbes; El-Rifai, Wael
Esophageal adenocarcinoma (EAC) is one of the two most common types of esophageal cancer with alarming increase in incidence and very poor prognosis. Aiming to detect EAC early, currently high-risk patients are monitored using an endoscopic-biopsy approach. However, this approach is prone to sampling error and interobserver variability. Diagnostic tissue biomarkers related to genomic and cell-cycle abnormalities have shown promising results, although with current technology these tests are difficult to implement in the screening of high-risk patients for early neoplastic changes. Differential miRNA profiles and aberrant protein glycosylation in tissue samples have been reported to improve performance of existing tissue-based diagnostic biomarkers. In contrast to tissue biomarkers, circulating biomarkers are more amenable to population-screening strategies, due to the ease and low cost of testing. Studies have already shown altered circulating glycans and DNA methylation in BE/EAC, whereas disease-associated changes in circulating miRNA remain to be determined. Future research should focus on identification and validation of these circulating biomarkers in large-scale trials to develop in vitro diagnostic tools to screen population at risk for EAC development. PMID:23576690
Shah, Alok Kishorkumar; Saunders, Nicholas A; Barbour, Andrew P; Hill, Michelle M
Background Despite many attempts to establish pre-treatment prognostic markers to understand the clinical biology of esophageal adenocarcinoma (EAC), validated clinical biomarkers or parameters remain elusive. We generated and analyzed tumor transcriptome to develop a practical biomarker prognostic signature in EAC. Methodology/Principal Findings Untreated esophageal endoscopic biopsy specimens were obtained from 64 patients undergoing surgery and chemoradiation. Using DNA microarray technology, genome-wide gene expression profiling was performed on 75 untreated cancer specimens from 64 EAC patients. By applying various statistical and informatical methods to gene expression data, we discovered distinct subgroups of EAC with differences in overall gene expression patterns and identified potential biomarkers significantly associated with prognosis. The candidate marker genes were further explored in formalin-fixed, paraffin-embedded tissues from an independent cohort (52 patients) using quantitative RT-PCR to measure gene expression. We identified two genes whose expression was associated with overall survival in 52 EAC patients and the combined 2-gene expression signature was independently associated with poor outcome (P<0.024) in the multivariate Cox hazard regression analysis. Conclusions/Significance Our findings suggest that the molecular gene expression signatures are associated with prognosis of EAC patients and can be assessed prior to any therapy. This signature could provide important improvement for the management of EAC patients.
Kim, Soo Mi; Park, Yun-Yong; Park, Eun Sung; Cho, Jae Yong; Izzo, Julie G.; Zhang, Di; Kim, Sang-Bae; Lee, Jeffrey H.; Bhutani, Manoop S.; Swisher, Stephen G.; Wu, Xifeng; Coombes, Kevin R.; Maru, Dipen; Wang, Kenneth K.; Buttar, Navtej S.; Ajani, Jaffer A.; Lee, Ju-Seog
Barrett's esophagus, a columnar metaplasia of the lower esophagus epithelium related to gastroesophageal reflux disease, is the strongest known risk factor for the development of esophageal adenocarcinoma (EAC). Understanding the signal transduction events involved in esophageal epithelium carcinogenesis mayprovide insights into the origins of EAC and maysuggest new therapies. To elucidate the molecular pathways of bile acid-induced tumorigenesis, the newly
Chia-Jui Yen; Julie G. Izzo; Dung-Fang Lee; Sushovan Guha; Jung-Mao Hsu; Hui-Lung Sun; Chao-Kai Chou; Navtej S. Buttar; Kenneth K. Wang; Peng Huang; Jaffer Ajani
The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter hypermethylation was examined by real-time methylation-specific polymerase chain reaction in 259 human esophageal tissues. Hypermethylation of this promoter showed highly discriminative receiver–operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from normal esophagus (NE) (P<0.001). NELL1
Z Jin; Y Mori; J Yang; F Sato; T Ito; Y Cheng; B Paun; J P Hamilton; T Kan; A Olaru; S David; R Agarwal; J M Abraham; D Beer; E Montgomery; S J Meltzer
Purpose Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrett’s esophagus (BE), a premalignant pathological change occurring in the lower end of esophagus. To identify BE patients at high risk of malignant transformation is essential to the prevention of EAC. Although microRNA (miRNA) expression signatures have been associated with the etiology and prognosis of several types of cancers, their roles in the development of EAC have not been extensively evaluated. Experimental Design In this study, we analyzed the expression patterns of 470 human miRNAs using Agilent miRNA microarray in 32 disease/normal-paired tissues from 16 patients diagnosed with BE of either low or high grade dysplasia, or EAC. Results Using unsupervised hierarchical clustering and class comparison analyses, we found that miRNA expression profiles in tissues of BE with high grade dysplasia were significantly different from their corresponding normal tissues. Similar findings were observed for EAC, but not for BE with low grade dysplasia. The expression patterns of selected miRNAs were further validated using quantitative reverse transcription real-time PCR in an independent set of 75 pairs of disease/normal tissues. Finally, we identified several miRNAs that were involved in the progressions from low grade dysplasia BE to EAC. Conclusions We showed that miRNAs were involved in the development and progression of EAC. The identified significant miRNAs may become potential targets for early detection, chemoprevention, and treatment of esophageal cancer.
Yang, Hushan; Gu, Jian; Wang, Kenneth K.; Zhang, Wei; Xing, Jinliang; Chen, Zhinan; Ajani, Jaffer A.; Wu, Xifeng
Background Esophageal cancer accounts for a considerable proportion of carcinomas of the upper gastrointestinal tract in African Americans.\\u000a Our aim was to describe the epidemiology of esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EA) among\\u000a African Americans in the last five decades.\\u000a \\u000a \\u000a \\u000a \\u000a Methods A total of 601 records of patients with documented esophageal cancer between 1959 and 2007 at Howard University
Hassan Ashktorab; Zahra Nouri; Mehdi Nouraie; Hadi Razjouyan; Edward E. Lee; Ehsan Dowlati; El-Waleed El-Seyed; Adeyinka Laiyemo; Hassan Brim; Duane T. Smoot
The generation and development of esophageal adenocarcinoma (EAC) are correlated with neuroimmunological factors. The aim of this study was to observe the effectiveness of the neurotransmitter arachidonic acid (AA) on two EAC cell lines, OE19 and SK-GT-4, as well as three isolated tumor-infiltrating lymphocytes (TIL1, 2 and 3). C-X-C chemokine receptor type 4 (CXCR-4) and tumor necrosis factor receptor 1 (TNFR1) expression, cell migration, necrosis, cytokine secretion and cytotoxicity of TILs were investigated. AA dose-dependently increased the migration of all cells. However, AA did not increase the percentage of cell death of the three TILs in the presence of a necrosis-inducing agent. AA dose-dependently increased the cytotoxicity of the three ??T cell-enriched TILs compared with the OE19 and SK-GT-4 cell lines. AA also dose-dependently increased the secretion of interferon-? (IFN-?) and TNF-? in TIL1 and 2. However, the cytokine secretion and cytotoxicity activity of TIL3 and ??T cell-enriched TIL3 were the lowest. Furthermore, the percentage of CD4+forkhead box p3 (Foxp3)+ regulatory T cells in TIL3 was the highest. The effect of AA on tumor cells and TILs is different. The degree of malignancy of the tumor and the ratio of regulatory T cells may be the main factors determining the function of AA.
SONG, WEI; JIANG, RUI; ZHAO, CHUNMING
Given the poor survival rate and efficacy of current therapy for esophageal adenocarcinoma (EAC), there is a need to identify and develop new therapeutic targets for treatment. Microarray analysis (Affymetrix U133A GeneChips, Robust Multi-Chip Analysis) was used to expression profile 11 normal squamous and 18 Barrett's esophagus biopsies, 7 surgically resected EACs and 3 EAC cell lines. Two hundred transcripts representing potential therapeutic targets were identified using the following criteria: significant overexpression in EAC by analysis of variance (p = 0.05, Benjamini Hochberg false discovery rate); 3-fold increase in EAC relative to normal and Barrett's esophagus and expression in at least 2 of the 3 EAC cell lines. From the list of potential targets we selected TNFRSF12A/Fn14/TWEAK receptor, a tumor necrosis factor super-family receptor, for further validation based on its reported role in tumor cell survival and potential as a target for therapy. Fn14 protein expression was confirmed in SEG-1 and BIC-1 cell lines, but Fn14 was not found to affect tumor cell survival after exposure to chemotherapeutics as expected. Instead, a novel role in EAC was discovered in transwell assays, in which modulating Fn14 expression affected tumor cell invasion. Fn14's potential as a therapeutic target was further supported by immunohistochemistry on a tissue microarray of patient samples that showed that Fn14 protein expression increased with disease progression in EAC. PMID:17594693
Watts, George S; Tran, Nhan L; Berens, Michael E; Bhattacharyya, Achyut K; Nelson, Mark A; Montgomery, Elizabeth A; Sampliner, Richard E
The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a 5-year survival rate of ~15%, the identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole-exome sequencing of 149 EAC tumor-normal pairs, 15 of which have also been subjected to whole-genome sequencing. We identify a mutational signature defined by a high prevalence of A>C transversions at AA dinucleotides. Statistical analysis of exome data identified 26 significantly mutated genes. Of these genes, five (TP53, CDKN2A, SMAD4, ARID1A and PIK3CA) have previously been implicated in EAC. The new significantly mutated genes include chromatin-modifying factors and candidate contributors SPG20, TLR4, ELMO1 and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 identifies increased cellular invasion. Therefore, we suggest the potential activation of the RAC1 pathway as a contributor to EAC tumorigenesis. PMID:23525077
Dulak, Austin M; Stojanov, Petar; Peng, Shouyong; Lawrence, Michael S; Fox, Cameron; Stewart, Chip; Bandla, Santhoshi; Imamura, Yu; Schumacher, Steven E; Shefler, Erica; McKenna, Aaron; Carter, Scott L; Cibulskis, Kristian; Sivachenko, Andrey; Saksena, Gordon; Voet, Douglas; Ramos, Alex H; Auclair, Daniel; Thompson, Kristin; Sougnez, Carrie; Onofrio, Robert C; Guiducci, Candace; Beroukhim, Rameen; Zhou, Zhongren; Lin, Lin; Lin, Jules; Reddy, Rishindra; Chang, Andrew; Landrenau, Rodney; Pennathur, Arjun; Ogino, Shuji; Luketich, James D; Golub, Todd R; Gabriel, Stacey B; Lander, Eric S; Beer, David G; Godfrey, Tony E; Getz, Gad; Bass, Adam J
Studies on experimental animals involving surgical procedures and\\/or nitrosamine treatment related to the etiology of esophageal adenocarcinoma 1 Abbreviations: Barrett's, Barrett's esophagus; EAC, esophageal adenocarcinoma; EC, esophageal cancer; ED, esophagoduodenostomy; EJ, esophagojejunostomy; ESC, esophageal squamous carcinoma; DMNM, 2,6-dimethylnitrosomorpholine; GC, gastric cancer; LES, lower esophageal sphincter; MNAN, methyl- n-amylnitrosamine; NSAID, non-steroidal anti-inflammatory drug; ROS, reactive oxygen species. 1
After a brief review of the epidemiology and etiology of lower esophageal adenocarcinoma (EAC), this paper describes long-term experiments on animals (mostly rats) demonstrating that reflux of duodenal contents into the stomach can induce gastric and pancreatic cancer, that gastric reflux into the esophagus can induce Barrett's esophagus; that esophagoduodenostomy to facilitate duodenal reflux into the esophagus, together with administration
Sidney S Mirvish
Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64±0.14 and 4.50±0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88±0.04 and 0.81±0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions.
Habibollahi, Peiman; Figueiredo, Jose-Luiz; Heidari, Pedram; Dulak, Austin M; Imamura, Yu; Bass, Adam J.; Ogino, Shuji; Chan, Andrew T; Mahmood, Umar
Background and Methods Esophageal adenocarcinoma (EAC) is characterized by a steep rise in incidence rates in the Western population. The unique miRNA signature that distinguishes EAC from other upper gastrointestinal cancers remains unclear. Herein, we performed a comprehensive microarray profiling for the specific miRNA signature associated with EAC. We validated this signature by qRT-PCR. Results Microarray analysis showed that 21 miRNAs were consistently deregulated in EAC. miR-194, miR-192, miR-200a, miR-21, miR-203, miR-205, miR-133b, and miR-31 were selected for validation using 46 normal squamous (NS), 23 Barrett’s esophagus (BE), 17 Barrett’s high grade dysplasia (HGD), 34 EAC, 33 gastric adenocarcinoma (GC), and 45 normal gastric (NG) tissues. The qRT-PCR analysis indicated that 2 miRNAs (miR-21 and miR-133b) were deregulated in both EAC and GC, and 6 miRNAs (up-regulated: miR-194, miR-31, miR-192, and miR-200a; down-regulated: miR-203 and miR-205) in EAC, as compared to BE but not in GC, indicating their potential unique role in EAC. Our data showed that miR-194, miR-192, miR-21, and miR-31 were up-regulated in BE adjacent to HGD lesions relative to isolated BE samples. Analysis of clinicopathological features indicated that down-regulation of miR-203 is significantly associated with progression and tumor stages in EAC. Interestingly, the overexpression levels of miR-194, miR-200a, and miR-192 were significantly higher in early EAC stages, suggesting that these miRNAs may be involved in EAC tumor development rather than progression. Conclusion Our findings demonstrate the presence of a unique miRNA signature for EAC. This may provide some clues for the distinct molecular features of EAC to be considered in future studies of the role of miRNAs in EAC and their utility as disease biomarkers.
Saad, Rama; Chen, Zheng; Zhu, Shoumin; Jia, Peilin; Zhao, Zhongming; Washington, M. Kay; Belkhiri, Abbes; El-Rifai, Wael
Background The US has experienced an alarming and unexplained increase in the incidence of esophageal adenocarcinoma (EAC) since the 1970s. A concurrent increase in obesity has led some to suggest a relationship between the two trends. We explore the extent of this relationship. Methods Using a previously validated disease simulation model of white males in the US, we estimated esophageal adenocarcinoma incidence 1973–2005 given constant obesity prevalence and low population progression rates consistent with the early 1970s. Introducing only the observed, rising obesity prevalence we calculated the incremental incidence caused by obesity. We compared these to esophageal adenocarcinoma incidence data from the National Cancer Institute’s SEER registry to determine obesity's contribution to the rise therein. Incidences were converted to absolute numbers of cases using US population data. Results Using constant obesity prevalence we projected a total of 30,555 EAC cases cumulatively over 1973–2005 and 1,151 in 2005 alone. Incorporating the observed obesity trend resulted in 35,767 cumulative EACs and 1,608 in 2005. Estimates derived from SEER data showed 111,223 cumulative and 7,173 cases in 2005. We conclude that the rise in obesity accounted for 6.5% of the increase in EAC cases that occurred from 1973–2005 and 7.6% in the year 2005. Conclusion Using published odds ratios for EAC among obese individuals, we found that only a small percentage of the rise in EAC incidence is attributable to secular trends in obesity. Impact Other factors, alone and in combination, should be explored as causes of the EAC epidemic.
Kong, Chung Yin; Nattinger, Kevin J.; Hayeck, Tristan J.; Omer, Zehra B.; Wang, Y. Claire; Spechler, Stuart J.; McMahon, Pamela M.; Gazelle, G. Scott; Hur, Chin
Purpose Esophageal adenocarcinoma (EAC) is a lethal malignancy that can develop from the premalignant condition, Barrett’s esophagus (BE). Currently, there are no validated simple methods to predict which patients will progress to EAC. A better understanding of the genetic mechanisms driving EAC tumorigenesis is needed to identify new therapeutic targets and develop biomarkers capable of identifying high-risk patients that would benefit from aggressive neoadjuvant therapy. We employed an integrative genomics approach to identify novel genes involved in EAC biology that may serve as useful clinical markers. Experimental Design Whole genome tiling-path array CGH was used to identify significant regions of copy number (CN) alteration in 20 EACs and 10 matching BE tissues. CN and gene expression data were integrated to identify candidate oncogenes within regions of amplification and multiple additional sample cohorts were assessed to validate candidate genes. Results We identified RFC3 as a novel, candidate oncogene activated by amplification in ~25% of EAC samples. RFC3 was also amplified in BE from a patient whose EAC harbored amplification, and was differentially expressed between non-malignant and EAC tissues. CN gains were detected in other cancer types and RFC3 knockdown inhibited proliferation and anchorage-independent growth of cancer cells with increased CN, but had little effect on those without. Moreover, high RFC3 expression was associated with poor patient outcome in multiple cancer types. Conclusions RFC3 is a candidate oncogene amplified in EAC. RFC3 DNA amplification is also prevalent in other epithelial cancer types and RFC3 expression could serve as a prognostic marker.
Lockwood, William W.; Thu, Kelsie L.; Lin, Lin; Pikor, Larissa A.; Chari, Raj; Lam, Wan L.; Beer, David G.
Barrett's esophagus (BE) is a metaplastic condition caused by chronic gastroesophageal reflux which represents an early step in the development of esophageal adenocarcinoma (EAC). Single-nucleotide polymorphism microarray (SNP-chip) analysis is a novel, precise, high-throughput approach to examine genomic alterations in neoplasia. Using 250K SNP-chips, we examined the neoplastic progression of BE to EAC, studying 11 matched sample sets: 6 sets of normal esophagus (NE), BE and EAC, 4 of NE and BE and 1 of NE and EAC. Six (60%) of 10 total BE samples and 4 (57%) of 7 total EAC samples exhibited 1 or more genomic abnormalities comprising deletions, duplications, amplifications and copy-number-neutral loss of heterozygosity (CNN-LOH). Several shared abnormalities were identified, including chromosome 9p CNN-LOH [2 BE samples (20%)], deletion of CDKN2A [4 BE samples (40%)] and amplification of 17q12-21.2 involving the ERBB2, RARA and TOP2A genes [3.1 Mb, 2 EAC (29%)]. Interestingly, 1 BE sample contained a homozygous deletion spanning 9p22.3-p22.2 (1.2 Mb): this region harbors only 1 known gene, basonuclin 2 (BNC2). Real-time PCR analysis confirmed the deletion of this gene and decreased the expression of BNC2 mRNA in the BE sample. Furthermore, transfection and stable expression of BNC2 caused growth arrest of OE33 EAC cells, suggesting that BNC2 functions as a tumor suppressor gene in the esophagus and that deletion of this gene occurs during the development of EAC. Thus, this SNP-chip analysis has identified several early cytogenetic events and novel candidate cancer-related genes that are potentially involved in the evolution of BE to EAC. PMID:19670330
Akagi, Tadayuki; Ito, Tetsuo; Kato, Motohiro; Jin, Zhe; Cheng, Yulan; Kan, Takatsugu; Yamamoto, Go; Olaru, Alexandru; Kawamata, Norihiko; Boult, Jessica; Soukiasian, Harmik J; Miller, Carl W; Ogawa, Seishi; Meltzer, Stephen J; Koeffler, H Phillip
The transcription factor, nuclear factor ?B (NF-?B), plays a central role as a key mediator of cell survival and proliferation, and its activation may confer increased tumor chemoresistance. Curcumin, an orally available naturally occurring compound, has been shown to inhibit NF-?B and has a potential role in cancer chemoprevention. We investigated the effects of curcumin on NF-?B activity, on cell viability, and as a chemosensitizing agent with 5-fluorouracil (5-FU) or cisplatin (CDDP) in esophageal adenocarcinoma (EAC). Oligonucleotide microarray analysis of 46 cases, consisting of Barrett metaplasia, low-grade dysplasia, high-grade dysplasia and EAC, showed increased expression of NF-?B and I?B kinase subunits and decreased effector caspase expression in EAC compared with Barrett metaplasia. Stromal expression of both I?B and phospho-I?B was detected in several EAC samples by tissue microarray analysis. Curcumin alone inhibited NF-?B activity and induced apoptosis in both Flo-1 and OE33 EAC cell lines as determined by Western blot analysis, NF-?B reporter assays, and Caspase-Glo 3/7 assays. It also increased 5-FU- and CDDP-induced apoptosis in both cell lines. These data suggest that activation of NF-?B and inhibition of apoptosis may play a role in the progression from Barrett metaplasia to EAC. In addition, curcumin, a well-known inhibitor of NF-?B activity, was shown to increase apoptosis and enhance both 5-FU- and CDDP-mediated chemosensitivity, suggesting that it may have potential application in the therapy of patients with EAC.
Hartojo, Wibisono; Silvers, Amy L; Thomas, Dafydd G; Seder, Christopher W; Lin, Lin; Rao, Hyma; Wang, Zhuwen; Greenson, Joel K; Giordano, Thomas J; Orringer, Mark B; Rehemtulla, Alnawaz; Bhojani, Mahaveer S; Beer, David G; Chang, Andrew C
Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Stage IB Esophageal Cancer; Stage IIA Esophageal Cancer; Stage IIB Esophageal Cancer; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer
A 71-year-old man presented with chief complains of hoarseness and dysphagia. He was diagnosed to have an advanced esophageal adenocarcinoma in the middle thoracic esophagus for which chemoradiation therapy was started. Partial response was observed and he was referred to our hospital thereafter. After detailed examination, he underwent a subtotal esophagectomy followed by two-field lymphadenectomy in May 2001. Histopathological examination revealed a complete response. Ten months later, hematological examination showed a high serum CEA level and CT scan disclosed mediastinal lymph node recurrences. He received a course of systemic chemotherapy so called FP therapy and five months later, a course of combination chemotherapy with 700 mg/m2 5-FU on days 1-5 and 70 mg/m2 nedaplatin on day 1 was administered. Because the high serum CEA level sustained afterward, FDG-PET was undertaken in March 2003. The right adrenal gland showed an intense abnormal FDG uptake and CT scan detected a low density mass in the area. Since no metastases could be identified in other sites, right adrenalectomy was performed. Pathological finding was poorly-differentiated tubular adenocarcinoma. Five years and eleven months after adrenalectomy, he died of pneumonia with no signs of recurrence. Surgical resection may contribute to improving the prognosis of solitary adrenal metastasis of esophageal cancer without the other noncurative factors. PMID:21224588
Saito, Hiroshige; Shuto, Kiyohiko; Ota, Takumi; Toma, Takayuki; Ohira, Gaku; Natsume, Toshiyuki; Uesato, Masaya; Akutsu, Yasunori; Kono, Tsuguaki; Matsubara, Hisahiro
Background Metallothionein 3 (MT3) maintains intracellular metal homeostasis and protects against reactive oxygen species (ROS)-induced DNA damage. In this study, we investigated the epigenetic alterations and gene expression of the MT3 gene in esophageal adenocarcinomas (EACs). Methods and Results Using quantitative bisulfite pyrosequencing, we detected unique DNA methylation profiles in the MT3 promoter region. The CpG nucleotides from ?372 to ?306 from the transcription start site (TSS) were highly methylated in tumor (n?=?64) and normal samples (n?=?51), whereas CpG nucleotides closest to the TSS (?4 and +3) remained unmethylated in all normal and most tumor samples. Conversely, CpG nucleotides in two regions (from ?139 to ?49 and +296 to +344) were significantly hypermethylated in EACs as compared to normal samples [FDR<0.001, ?log10(FDR)>3.0]. The DNA methylation levels from ?127 to ?8 CpG sites showed the strongest correlation with MT3 gene expression (r?=??0.4, P<0.0001). Moreover, the DNA hypermethylation from ?127 to ?8 CpG sites significantly correlated with advanced tumor stages and lymph node metastasis (P?=?0.005 and P?=?0.0313, respectively). The ChIP analysis demonstrated a more repressive histone modification (H3K9me2) and less active histone modifications (H3K4me2, H3K9ace) in OE33 cells than in FLO-1 cells; concordant with the presence of higher DNA methylation levels and silencing of MT3 expression in OE33 as compared to FLO-1 cells. Treatment of OE33 cells with 5-Aza-deoxycitidine restored MT3 expression with demethylation of its promoter region and reversal of the histone modifications towards active histone marks. Conclusion In summary, EACs are characterized by frequent epigenetic silencing of MT3. The choice of specific regions in the CpG island is a critical step in determining the functional role and prognostic value of DNA methylation in cancer cells.
Peng, DunFa; Hu, Tian-Ling; Jiang, Aixiang; Washington, Mary Kay; Moskaluk, Christopher A.; Schneider-Stock, Regine; El-Rifai, Wael
Esophageal Barrett's adenocarcinoma (BA) develops through a multistage process, which is associated with the transcriptional silencing of tumor-suppressor genes by promoter CpG island hypermethylation. In this study, we explored the promoter hypermethyla- tion and protein expression of proapoptotic death- associated protein kinase (DAPK) during the multistep Barrett's carcinogenesis cascade. Early BA and paired samples of premalignant lesions of 61 patients
Doerthe Kuester; Altaf A. Dar; Christopher C. Moskaluk; Sabine Krueger; Frank Meyer; Roland Hartigb; Manfred Stolte; Peter Malfertheiner; Hans Lippert; Albert Roessner; Wael El-Rifai; Regine Schneider-Stock
Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.
Nancarrow, Derek J.; Clouston, Andrew D.; Smithers, B. Mark; Gotley, David C.; Drew, Paul A.; Watson, David I.; Tyagi, Sonika; Hayward, Nicholas K.; Whiteman, David C.
Nitric oxide (NO) has been implicated as a potential causative factor for endogenous p53 mutations in gastrointestinal malignancy. To investigate the role of NO in esophageal adenocarcinoma (EADC), we studied patterns of p53 mutations, expression of inducible nitric oxide synthase (iNOS) and the tissue accumulation of nitrotyrosine (NTS), a stable reaction product of NO and a marker for cellular protein damage, in human premalignant and malignant esophageal epithelia. Tissues were obtained from patients with gastroesophageal reflux disease (GERD)-induced esophagitis (n = 76), Barrett's esophagus (BE; n = 119) and primary EADC (n = 54). DNA sequencing was used to characterize p53 mutations, RT-PCR to study iNOS mRNA expression, and immunohistochemistry to study NTS. Relative to self-matched normal epithelia, a progressive increase in iNOS mRNA expression was seen in GERD (30%; 23/76), BE (48%; 57/119), and EADC (63%; 34/54) tissues (P < 0.001). Among patients with EADC, elevated levels of NTS immunoreactivity were more frequent in tumors with p53 mutations (11/21; 52%) compared with tumors with wild-type p53 (9/33; 27%; P = 0.063), and specifically in tumors with p53 mutations at CpG dinucleotides (10/12; 83%) compared with non-CpG p53 mutations (1/9; 11%; P = 0.008). The increasing frequency of iNOS (mRNA) overexpression in GERD, BE and EADC supports the hypothesis that an active inflammatory process, most likely a consequence of GERD, underlies molecular progression to EADC. The highly significant association between NTS, reflecting chronic NO-induced cellular protein damage, and endogenous p53 mutations at CpG dinucleotides, provides further evidence for a molecular link between chronic inflammation and esophageal malignancy. PMID:17849424
Vaninetti, Nadine M; Geldenhuys, Laurette; Porter, Geoffrey A; Risch, Harvey; Hainaut, Pierre; Guernsey, Duane L; Casson, Alan G
BackgroundGastroesophageal reflux is a frequent problem after esophageal atresia (EA) repair. Our aim was to determine the prevalence of esophagitis and Barrett esophagus more than 10 years after repair of EA.
Jacqueline A. Deurloo; Seine Ekkelkamp; Jan A. J. M. Taminiau; C. M. Frank Kneepkens; Fibo W. J. ten Kate; Joep F. W. M. Bartelsman; Dink A. Legemate; Daniel C. Aronson
Trimodality therapy with neoadjuvant chemoradiation followed by surgery significantly improves the survival of locally advanced (clinical stage IIA-III) esophageal cancer patients compared to treatment with surgery alone. This has resulted in an increased use of neoadjuvant therapy in recent years, yet little is known regarding how this increase has impacted the utilization of surgery in the treatment of locally advanced disease. Although previous reports of experimental protocols suggest that 90-95% of patients complete trimodality therapy including a surgical resection, trimodality therapy completion among adenocarcinoma patients eligible for curative resection has not been evaluated in a nonprotocol setting. We sought to (i) assess the completion of trimodality therapy among locally advanced esophageal adenocarcinoma patients; (ii) characterize the reasons for avoiding surgery; and (iii) identify factors associated with failure to complete trimodality therapy. We identified 296 patients with locally advanced esophageal adenocarcinoma eligible for trimodality therapy at our institution. All patients were evaluated in a multidisciplinary setting and considered eligible for curative resection after initial staging and physiologic assessment. Multivariable logistic regression was used to identify factors associated with failure to complete trimodality therapy. Of 296 trimodality-eligible patients, 33% (97/296) did not complete trimodality therapy. Reasons for not undergoing surgery included patient choice (27.8%, 27/97), distant progression of disease during chemoradiation (23.7%, 23/97), and physician preference for surveillance (23.7%, 23/97). In addition, 17.5% (17/97) of patients had physical deterioration in performance status, and treatment-related deaths occurred in 7.2% (7/97) prior to surgery. In the total study population (n = 296), multivariable logistic regression identified older age (?70 years: odds ratio [OR] = 6.611, 95% confidence interval [CI]: 2.900-15.071), pretreatment standard uptake value (6.8-10.1: OR = 2.393, 95% CI: 1.050-5.455; ?15.8: OR = 3.623, 95% CI: 1.604-8.186), and a radiation dose of 50.4?Gy (OR = 5.312, 95% CI: 2.365-11.929) as being significantly associated with failure to complete trimodality therapy. Among the subgroup of patients that successfully completed chemoradiation (n = 266), older patients (?70 years: OR = 9.606, 95% CI: 3.637-25.372), those with a comorbidity score of 2 or higher (OR = 4.059, 95% CI: 1.257-13.103), and those that received a radiation dose of 50.4?Gy (OR = 4.878, 95% CI: 1.974-12.054) were at a significantly higher risk of not completing trimodality therapy. Trimodality therapy completion among patients with locally advanced esophageal adenocarcinoma in a nonprotocol setting is considerably lower than what has previously been reported in clinical trials. Our findings suggest that a selective approach to surgery is commonly utilized in clinical practice. Trimodality-eligible patients that are older and have a higher comorbidity score are at risk for not completing trimodality therapy. PMID:23350713
Murphy, C C; Hofstetter, W L; Correa, A M; Ajani, J A; Komaki, R U; Swisher, S G
We report a case of a granular cell tumor colliding with intramucosal adenocarcinoma of the esophagus. A 58-year-old white was found to have a 5 mm nodule in the distal esophagus detected by upper gastrointestinal endoscopy performed as part of the workup of long standing reflux. Endoscopic biopsies revealed intramucosal adenocarcinoma arising in the setting of Barrett’s esophagus. The adenocarcinoma infiltrated a granular cell tumor also present at the nodular site. Endoscopic mucosal resection using Duette band ligation and hot snare electrocautery was performed. Margins were negative for both tumors, and endoscopic surveillance for recurrence is planned.
Martin, Jeremiah T; Fiedler, Paul; Jaffe, Philip E
The occurrence of phenotypic differences between monozygotic (MZ) twins is commonly attributed to environmental factors, assuming that MZ twins have a complete identical genetic make-up. Yet, recently several lines of evidence showed that both genetic and epigenetic factors could have a role in phenotypic discordance after all. A high occurrence of copy number variation (CNV) differences was observed within MZ twin pairs discordant for Parkinson's disease, thereby stressing on the importance of post-zygotic mutations as disease-predisposing events. In this study, the prevalence of discrepant CNVs was analyzed in discordant MZ twins of the Esophageal Atresia (EA) and Congenital Diaphragmatic Hernia (CDH) cohort in the Netherlands. Blood-derived DNA from 11 pairs (7 EA and 4 CDH) was screened using high-resolution SNP arrays. Results showed an identical copy number profile in each twin pair. Mosaic chromosome gain or losses could not be detected either with a detection threshold of 20%. Some of the germ-line structural events demonstrated in five out of eleven twin pairs could function as a susceptible genetic background. For example, the 177-Kb loss of chromosome 10q26 in CDH pair-3 harbors the TCF7L2 gene (Tcf4 protein), which is implicated in the regulation of muscle fiber type development and maturation. In conclusion, discrepant CNVs are not a common cause of twin discordancy in these investigated congenital anomaly cohorts.
Veenma, Danielle; Brosens, Erwin; de Jong, Elisabeth; van de Ven, Cees; Meeussen, Connie; Cohen-Overbeek, Titia; Boter, Marjan; Eussen, Hubertus; Douben, Hannie; Tibboel, Dick; de Klein, Annelies
Background: Aberrant expression of small noncoding endogenous RNA molecules known as microRNAs (miRNAs) is documented to occur in multiple cancer types including esophageal adencarcinoma (EAC) and its only known precursor, Barrett's esophagus (BE). Recent studies have linked dysregulation of specific miRNAs to histological grade, neoplastic progression and metastatic potential. Materials and Methods: Herein, we present a summary of previously reported dysregulated miRNAs in BE and EAC tissues as well as EAC cell lines and evaluate a cranberry proanthocyanidin rich extract's (C-PAC) ability to modulate miRNA expression patterns of three human EAC cell lines (JHEso-Ad-1, OE33 and OE19). Results: A review of 13 published studies revealed dysregulation of 87 miRNAs in BE and EAC tissues, whereas 52 miRNAs have been reported to be altered in BE or EAC cell lines, with 48% overlap with miRNA changes reported in tissues. We report for the first time C-PAC–induced modulation of five miRNAs in three EAC cell lines resulting in 26 validated gene targets and identification of key signaling pathways including p53, angiogenesis, T-cell activation and apoptosis. Additionally, mutiple cancer related networks were ideintified as modulated by C-PAC utilizing Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein Analysis Through Evolutionary Relationships (PANTHER), and MetaCore analysis tools. Conclusions: Study results support the cancer inhibitory potential of C-PAC is in part attributable to C-PAC's ability to modify miRNA profiles within EAC cells. A number of C-PAC–modulated miRNAs have been been identified as dysregulated in BE and EAC. Further insights into miRNA dysregulation and modulation by select cancer preventive agents will support improved targeted interventions in high-risk cohorts.
Kresty, Laura A.; Clarke, Jennifer; Ezell, Kristin; Exum, Amy; Howell, Amy B.; Guettouche, Toumy
In Western countries the incidence of the esophageal adenocarcinoma (EAC) has risen at a more rapid rate than that of any other malignancy. Despite intensive therapies this cancer is associated with extreme high morbidity and mortality. For this reason, novel effective therapeutic strategies are urgently required. Dendritic Cell (DC)-based immunotherapy is a promising novel treatment strategy, which combined with other anti-cancer strategies has been proven to be beneficial for cancer patients. Curcumin (diferuloylmethane), is a natural polyphenol that is known for its anti-cancer effects however, in it's free form, curcumin has poor bioavailability. The aim of this study was to investigate whether using a highly absorptive form of curcumin, dispersed with colloidal nano-particles, named Theracurmin would be more effective against EAC cells and to analyze if this new compound affects DC-induced T cell response. As a result, we show efficient uptake of nano-curcumin by the EAC cell lines, OE33, and OE19. Moreover, nano-curcumin significantly decreased the proliferation of the EAC cells, while did not affect the normal esophageal cell line HET-1A. We also found that nano-curcumin significantly up-regulated the expression of the co-stimulatory molecule CD86 in DCs and significantly decreased the secretion of pro-inflammatory cytokines from in vitro activated T cells. When we combined T cells with nano-curcumin treatment in OE19 and OE33, we found that the basic levels of T cell induced cytotoxicity of 6.4 and 4.1%, increased to 15 and 13%, respectively. In conclusion, we found that nano-curcumin is effective against EAC, sensitizes EAC cells to T cell induced cytotoxicity and decreases the pro-inflammatory signals from T cells. Combining DC immunotherapy with nano-curcumin is potentially a promising approach for future treatment of EAC. PMID:23755374
Milano, Francesca; Mari, Luigi; van de Luijtgaarden, Wendy; Parikh, Kaushal; Calpe, Silvia; Krishnadath, Kausilia K
Neoplastic progression is an evolutionary process driven by the generation of clonal diversity and natural selection on that diversity within a neoplasm. We hypothesized that clonal diversity is associated with risk of progression to cancer. We obtained molecular data from a cohort of 239 participants with Barrett's esophagus, including microsatellite shifts and loss of heterozygosity, DNA content tetraploidy and aneuploidy, methylation, and sequence mutations. Using these data, we tested all major diversity measurement methods, including genetic divergence and entropy-based measures, to determine which measures are correlated with risk of progression to esophageal adenocarcinoma. We also tested whether the use of different sets of loci and alterations to define clones (e.g., selectively advantageous versus evolutionarily neutral) improved the predictive value of the diversity indices. All diversity measures were strong and highly significant predictors of progression (Cox proportional hazards model, P < 0.001). The type of alterations evaluated had little effect on the predictive value of most of the diversity measures. In summary, diversity measures are robust predictors of progression to cancer in this cohort. PMID:20947487
Merlo, Lauren M F; Shah, Najaf A; Li, Xiaohong; Blount, Patricia L; Vaughan, Thomas L; Reid, Brian J; Maley, Carlo C
Although recent studies suggest that high intakes of meat and heme iron are risk factors for several types of cancer, studies in relation to esophageal adenocarcinoma (EAC) are scarce. Previous results in the European Prospective Investigation into Cancer and Nutrition (EPIC) based on a relatively small number of cases suggested a positive association between processed meat and EAC. In this study, we investigate the association between intake of different types of meats and heme iron intake and EAC risk in a larger number of cases from EPIC. The study included 481,419 individuals and 137 incident cases of EAC that occurred during an average of 11 years of follow-up. Dietary intake of meat (unprocessed/processed red and white meat) was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat. After adjusting for relevant confounders, we observed a statistically significant positive association of EAC risk with heme iron and processed meat intake, with HR: 1.67, 95% CI: 1.05-2.68 and HR: 2.27, 95% CI:1.33-3.89, respectively, for comparison of the highest vs. lowest tertile of intake. Our results suggest a potential association between higher intakes of processed meat and heme iron and risk of EAC. PMID:23728954
Jakszyn, Paula; Luján-Barroso, Leila; Agudo, Antonio; Bueno-de-Mesquita, H Bas; Molina, Esther; Sánchez, M José; Fonseca-Nunes, Ana; Siersema, Peter D; Matiello, Amalia; Tumino, Rosario; Saieva, Calogero; Pala, Valeria; Vineis, Paolo; Boutron-Ruault, Marie-Christine; Racine, Antoine; Bastide, Nadie; Travis, Ruth C; Khaw, Kay-Tee; Riboli, Elio; Murphy, Neil; Vergnaud, Anne-Claire; Trichopoulou, Antonia; Valanou, Elissavet; Oikonomidou, Edespina; Weiderpass, Elisabete; Skeie, Guri; Johansen, Dorthe; Lindkvist, Björn; Johansson, Mattias; Duarte-Salles, Talita; Freisling, Heinz; Barricarte, Aurelio; M Huerta, Jose; Amiano, Pilar; Tjonneland, Anne; Overvad, Kim; Kuehn, Tilman; Grote, Verena; Boeing, Heiner; Peeters, Petra Hm; A González, Carlos
The incidence of esophageal adenocarcinoma (EAC) is increasing significantly throughout the developed world. As yet, there are no proven chemopreventive strategies. In laboratory studies, aspirin, non-steroidal anti-inflammatory drugs and statins have promising chemopreventive actions. Several observational studies support a protective effect of aspirin and non-steroidal anti-inflammatory drugs, but there are only limited clinical data exploring the potential protective effect of statins. We conducted a case-control study examining aspirin and statin use in patients with EAC. Cancer cases were compared against age-sex-matched controls attending for diagnostic upper gastrointestinal endoscopy. Risk factor and drug exposure were established using standardized interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. A total of 112 cases and 448 controls were enrolled. Statin use was associated with a significantly lower incidence of EAC (odds ratio 0.52, 95% confidence interval 0.27-0.92). Aspirin use was also associated with apparent protection against EAC (odds ratio 0.68, 95% confidence interval 0.28-0.92), and a significantly greater effect was seen with the combination of statin plus aspirin (odds ratio 0.27, 95% confidence interval 0.05-0.67). There was a significant trend for greater risk reduction with longer duration and higher doses of statin use. Simvastatin comprised the majority of statin use, but similar effects were seen with simvastatin and non-simvastatin agents. In this observational study, patients regularly using statins or aspirin had a lower incidence of EAC. Statins may have clinically useful effects in preventing the development of EAC. PMID:22989236
Beales, I L P; Vardi, I; Dearman, L; Broughton, T
Esophageal adenocarcinoma (EAC) arises in the backdrop of reflux-induced metaplastic phenomenon known as Barrett esophagus. The prognosis of advanced EAC is dismal, and there is an urgent need for identifying molecular targets for therapy. Serial Analysis of Gene Expression (SAGE) was performed on metachronous mucosal biopsies from a patient who underwent progression to EAC during endoscopic surveillance. SAGE confirmed significant upregulation of Axl "tags" during the multistep progression of Barrett esophagus to EAC. In a cohort of 92 surgically resected EACs, Axl overexpression was associated with shortened median survival on both univariate (p < 0.004) and multivariate (p < 0.036) analysis. Genetic knockdown of Axl receptor tyrosine kinase (RTK) function was enabled in two EAC lines (OE33 and JH-EsoAd1) using lentiviral short hairpin RNA (shRNA). Genetic knockdown of Axl in EAC cell lines inhibited invasion, migration, and in vivo engraftment, which was accompanied by downregulation in the activity of the Ral GTPase proteins (RalA and RalB). Restoration of Ral activation rescued the transformed phenotype of EAC cell lines, suggesting a novel effector mechanism for Axl in cancer cells. Pharmacological inhibition of Axl was enabled using a small molecule antagonist, R428 (Rigel Pharmaceuticals). Pharmacological inhibition of Axl with R428 in EAC cell lines significantly reduced anchorage-independent growth, invasion and migration. Blockade of Axl function abrogated phosphorylation of ERBB2 (Her-2/neu) at the Tyr877 residue, indicative of receptor crosstalk. Axl RTK is an adverse prognostic factor in EAC. The availability of small molecule inhibitors of Axl function provides a tractable strategy for molecular therapy of established EAC. PMID:20818175
Hector, Alvarez; Montgomery, Elizabeth A; Karikari, Collins; Canto, Marcia; Dunbar, Kerry B; Wang, Jean S; Feldmann, Georg; Hong, Seung-Mo; Haffner, Michael C; Meeker, Alan K; Holland, Sacha J; Yu, Jiaxin; Heckrodt, Thilo J; Zhang, Jing; Ding, Pingyu; Goff, Dane; Singh, Rajinder; Roa, Juan Carlos; Marimuthu, Arivusudar; Riggins, Gregory J; Eshleman, James R; Nelkin, Barry D; Pandey, Akhilesh; Maitra, Anirban
Purpose We examined the frequency, tumor characteristics, and prognostic impact of HER2 protein expression and gene amplification in patients with curatively resected esophageal adenocarcinoma (EAC). Experimental Design HER2 expression was analyzed by immunohistochemistry (IHC) in surgical EAC specimens (n=713). Gene amplification was examined by fluorescence in situ hybridization (FISH) in a large subset (n=344). Most tumors were T3–4 (66%) or node-positive (72%); 95% were located in the esophagus or gastroesophageal junction. No patient received neoadjuvant therapy. Cox models were used. Results Overall, 17% of EACs were HER2-positive (ie, IHC3+ or IHC2+ with amplification), with strong agreement between HER2 amplification (HER2/CEP17 ratio ?2) and expression (?=.83). HER2-positivity was significantly associated with lower tumor grade, less invasiveness, fewer malignant nodes, and the presence of adjacent Barrett’s esophagus (BE). EACs with BE had higher odds of HER2-positivity compared to EACs without BE, independent of pathologic features (odds ratio 1.8 [95% confidence interval (CI) 1.1–2.8], p=.014). Among all cases, HER2-positivity was significantly associated with disease-specific survival (DSS) in a manner that differed by the presence or absence of BE (p for interaction=.0047). In EACs with BE, HER2-positivity was significantly associated with improved DSS (hazard ratio 0.54 [95% CI 0.35–0.84], p=.0065) and overall survival (p=.0022) independent of pathologic features, but was not prognostic among EACs without BE. Conclusions HER2-positivity was demonstrated in 17% of resected EACs and associated with reduced tumor aggressiveness. EACs with BE had nearly twice the odds of being HER2-positive and, within this subgroup, HER2-positivity was independently associated with improved survival.
Yoon, Harry H.; Shi, Qian; Sukov, William R.; Wiktor, Anne E.; Khan, Maliha; Sattler, Christopher A.; Grothey, Axel; Wu, Tsung-Teh; Diasio, Robert B.; Jenkins, Robert B.; Sinicrope, Frank A.
Esophageal adenocarcinomas (EACs) are poorly responsive to chemotherapeutics. This study aimed to determine the levels of Aurora kinas A (AURKA) and the therapeutic potential of MLN8237, an investigational AURKA inhibitor, alone and in combination with Cisplatin. Using quantitative real time polymerase chain reaction we detected frequent AURKA gene amplification (15/34, 44%) and mRNA overexpression (37/44, 84%) in EACs (p<0.01). Immunohistochemistry analysis demonstrated overexpression of AURKA in more than two-thirds of EACs tissue samples (92/132, 70%) (p<0.001). Using FLO-1, OE19 and OE33 EAC cell lines, with constitutive AURKA overexpression and mutant-p53, we observed inhibition of colony formation with a single treatment of 0.5?M MLN8237 (p<0.05). This effect was further enhanced in combination with 2.5?M Cisplatin (p<0.001). 24hrs after treatment with the MLN8237 or MLN8237 and Cisplatin, cell cycle analyses demonstrated a sharp increase in the percentage of polyploid cells (p<0.001). This was followed by an increase in the percentage of cells in the sub-G1-phase at 72hrs, concordant with the occurrence of cell death (p<0.001). Western blot analysis demonstrated higher induction of TAp73?, PUMA, NOXA, cleaved caspase 3 and cleaved PARP with the combined treatment, as compared to a single agent treatment. Using xenograft models, we demonstrated an enhanced anti-tumor role for the MLN8237 and Cisplatin combination, as compared to single agent treatments (p<0.001). In conclusion, this study demonstrates frequent overexpression of AURKA and suggests that MLN8237 could be an effective anti-tumor agent, which can be combined with CDDP for a better therapeutic outcome in EACs.
Sehdev, Vikas; Peng, DunFa; Soutto, Mohammed; Washington, M. Kay; Revetta, Frank; Ecsedy, Jeffrey; Zaika, Alexander; Tilman, Rau; Schneider-Stock, Regine; Belkhiri, Abbes; El-Rifai, Wael
Purpose Chromosomal gain at 7q21 is a frequent event in esophageal adenocarcinoma (EAC). However, this event has not been mapped with fine resolution in a large EAC cohort and its association with clinical endpoints and functional relevance are unclear. Experimental design We used a cohort of 116 patients to fine map the 7q21 amplification using SNP microarrays. Prognostic significance and functional role of 7q21 amplification and its gene expression were explored. Results Amplification of the 7q21 region was observed in 35% of tumors with a focal, minimal amplicon containing 6 genes. 7q21 amplification was associated with poor survival and analysis of gene expression identified CDK6 as the only gene in the minimal amplicon whose expression was also associated with poor survival. A low level amplification (10%) was observed at the 12q13 region containing the CDK6 homolog, CDK4. Both amplification and expression of CDK4 correlated with poor survival. A combined model of both CDK6 and CDK4 expression is a superior predictor of survival than either alone. Specific knockdown of CDK4 and/or CDK6 by siRNAs shows that they are required for proliferation of EAC cells and that their function is additive. PD-0332991 targets the kinase activity of both molecules and suppresses proliferation and anchorage-independence of EAC cells through activation of the pRB pathway. Conclusions We suggest that CDK6 is the driver of 7q21 amplification and that both CDK4 and CDK6 are prognostic markers and bona fide oncogenes in EAC. Targeting these molecules may constitute a viable new therapy for this disease.
Ismail, Amin; Bandla, Santhoshi; Reveiller, Marie; Toia, Liana; Zhou, Zhongren; Gooding, William E.; Kalatskaya, Irina; Stein, Lincoln; D'Souza, Mary; Litle, Virginia R.; Peters, Jeffrey H.; Pennathur, Arjun; Luketich, James D.; Godfrey, Tony E.
Background And Objective Two recent genome-wide association studies have identified a shared susceptibility variation PLCE1 rs2274223 for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). Subsequent case-control studies have reported this association in other populations. However, the findings were controversial and the effect remains undetermined. Our aim is to provide a precise quantification of the association between PLCE1 rs2274223 variation and the risk of ESCC and GCA. Methods Studies were identified by a literature search in MEDLINE and EMBASE databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association in allele, dominant, recessive, homozygous, and heterozygous models. Results Ten articles were identified, including 22156 ESCC cases and 28803 controls, 5197 GCA cases and 17613 controls. Overall, PLCE1 rs2274223 G allele (G vs. A: OR=1.26, 95% CI: 1.15-1.39 for ESCC; OR=1.51, 95% CI: 1.35–1.69 for GCA) and its carrier (GG +AG vs. AA: OR = 1.23; 95% CI =1.02-1.49 for ESCC; OR =1.62; 95% CI =1.15-2.29 for GCA) were significantly associated with the risk of ESCC and GCA. In stratified analysis by ethnicity, significant association of PLCE1 rs2274223 G allele and the risk of ESCC (OR=1.33, 95% CI 1.21–1.45) and GCA (OR =1.56, 95% CI: 1.47-1.64) was observed in Chinese population. Conclusions Our meta-analysis results indicated that PLCE1 rs2274223 G allele significantly contributed to the risk of ESCC and GCA, especially in Chinese population.
Mai, Ruiqin; Cheng, Yabin; Huang, Yuanshen; Zhang, Guohong
Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage III Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer
Background Recent data in esophageal cancer suggests the variant allele of a single-nucleotide polymorphism (SNP) in XRCC1 may be associated with resistance to radiochemotherapy. However, this SNP has not been assessed in a histologically homogeneous clinical trial cohort that has been treated with a uniform approach. In addition, whether germline DNA may serve as a surrogate for tumor genotype at this locus is unknown in this disease. Our objective was to assess this SNP in relation to the pathologic complete response (pCR) rate in subjects with esophageal adenocarcinoma who received cisplatin-based preoperative radiochemotherapy in a multicenter clinical trial (Eastern Cooperative Oncology Group 1201). As a secondary aim, we investigated the rate of allelic imbalance between germline and tumor DNA. Methods Eighty-one eligible treatment-naďve subjects with newly diagnosed resectable esophageal adenocarcinoma received radiotherapy (45 Gy) concurrent with cisplatin-based chemotherapy, with planned subsequent surgical resection. The primary endpoint was pCR, defined as complete absence of tumor in the surgical specimen after radiochemotherapy. Using germline DNA from 60 subjects, we examined the base-excision repair SNP, XRCC1 Arg399Gln, and 4 other SNPs in nucleotide excision (XPD Lys751Gln and Asp312Asn, ERCC1 3' flank) and double-stranded break (XRCC2 5' flank) repair pathways, and correlated genotype with pCR rate. Paired tumor tissue was used to estimate the frequency of allelic imbalance at the XRCC1 SNP. Results The variant allele of the XRCC1 SNP (399Gln) was detected in 52% of subjects. Only 6% of subjects with the variant allele experienced a pCR, compared to 28% of subjects without the variant allele (odds ratio 5.37 for failing to achieve pCR, p = 0.062). Allelic imbalance at this locus was found in only 10% of informative subjects, suggesting that germline genotype may reflect tumor genotype at this locus. No significant association with pCR was noted for other SNPs. Conclusions Assessed for the first time in a prospective, interventional trial cohort of esophageal adenocarcinoma, XRCC1 399Gln was associated with resistance to radiochemotherapy. Further investigation of this genetic variation is warranted in larger cohorts. In addition, these data indicate that germline genotype may serve as a surrogate for tumor genotype at this locus.
Background Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor prognosis, which frequently exhibits HER-2 gene amplification. Trastuzumab, the humanized antibody against HER-2, has potent growth inhibitory effects on HER-2 overexpressing cancers. One effect of trastuzumab is that it causes HER-2 receptor internalization and degradation, enhancing presentation of HER-2 epitopes on MHC-Class I molecules. This enhances the ability of HER-2 specific cytotoxic T lymphocytes (CTLs) to recognize and kill cancer cells. Novel strategies targeting the HER-2 receptor either directly by trastuzumab and/or indirectly by inducing a CTL response against HER-2 epitopes with, for instance, DC immunotherapy and consequently combining these strategies might prove to be very effective. Methodology/Principal Findings In this study we report that trastuzumab has potent growth inhibitory effects on two HER-2 overexpressing EAC cell lines OE33 and OE19. However, we found that trastuzumab and HER-2 specific CTLs act synergistically in inducing tumor lysis in OE33 but not in OE19. We discovered that in OE19 this deficient response is due to a down-regulation of the Transporter Associated with Antigen Processing-2 (TAP-2). TAP-2 is an important member of the Antigen Processing Machinery (APM), and is one of the essential elements for loading antigens on MHC class I molecules. Importantly, we demonstrated that by inducing re-expression of TAP-2 in OE19 with INF-? treatment or by incubating the cells with INF-? producing CTLs, the specific anti HER-2 CTL tumor lysis response and synergistic effect with trastuzumab can be restored. Conclusion An inefficient response of HER-2 overexpressing EAC to trastuzumab and/or DC immunotherapy can be due to a down-regulated TAP-2 expression and thus a deficient APM. Future studies combining trastuzumab with IFN-? and/or immune-therapies inducing potent anti HER-2 CTL responses could lead to an effective combinatorial strategy for successful treatment of HER-2 overexpressing but APM defective cancers.
Milano, Francesca; Guarriera, Mirta; Rygiel, Agnieszka M.; Krishnadath, Kausilia K.
Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer
The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter hypermethylation was examined by real-time methylation-specific polymerase chain reaction in 259 human esophageal tissues. Hypermethylation of this promoter showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from normal esophagus (NE) (P<0.001). NELL1 normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's (D) and EAC than in NE (P<0.0000001). NELL1 hypermethylation frequency was zero in NE but increased early during neoplastic progression, to 41.7% in BE from patients with Barrett's alone, 52.5% in D and 47.8% in EAC. There was a significant correlation between NELL1 hypermethylation and BE segment length. Three (11.5%) of 26 ESCCs exhibited NELL1 hypermethylation. Survival correlated inversely with NELL1 hypermethylation in patients with stages I-II (P=0.0264) but not in stages III-IV (P=0.68) EAC. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2'-deoxycytidine reduced NELL1 methylation and increased NELL1 mRNA expression. NELL1 mRNA levels in EACs with an unmethylated NELL1 promoter were significantly higher than those in EACs with a methylated promoter (P=0.02). Promoter hypermethylation of NELL1 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker of poor prognosis in early-stage EAC. PMID:17452981
Jin, Z; Mori, Y; Yang, J; Sato, F; Ito, T; Cheng, Y; Paun, B; Hamilton, J P; Kan, T; Olaru, A; David, S; Agarwal, R; Abraham, J M; Beer, D; Montgomery, E; Meltzer, S J
Background Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett's esophagus (BE) regarded as precancerous lesion. Matrix metalloproteinases (MMPs) might play a role during the multistep carcinogenetic process. Methods Expression of MMP-1 and -13 was analyzed in esophageal cancer (n = 41 EAC with BE, n = 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC), furthermore in BE without intraepithelial neoplasia (IN) (n = 18), and the cell line OE-33. MMP-1 was co-labelled with Ki-67 (proliferation), Cdx-2 (marker for intestinal metaplasia, BE) and analyzed on mRNA level. MMP-1 staining results were correlated with clinicopatholocical parameters. Results On protein level, MMP-1 expression was found in 39 of 41 (95%) EAC with BE, in 19 of 19 (100%) EAC without BE, in 6 of 10 (60%) ESCC, and in 10 of 18 (56%) BE without IN. No expression of MMP-13 was found in these specimens. Quantification showed 48% MMP-1 positive cells in EAC with BE, compared to 35% in adjacent BE (p < 0.05), 44% in EAC without BE, 32% in ESCC, and 4% in BE without IN. Immunofluorescence double staining experiments revealed increased MMP-1 expressing in proliferating cells (MMP-1+/Ki-67+) (r = 0.943 for BE and r = 0.811 for EAC). On mRNA-level, expression of MMP-1 was significantly higher in EAC compared to BE (p = 0.01) and confirmed immunohistochemical staining results. High MMP-1 levels were associated with lymph node metastases but not with poorer survival (p = 0.307). Conclusions Our findings suggest that MMP-1 plays a role as preinvasive factor in BE-associated EAC. Expression of MMP-1 in proliferating BE and EAC cells suggest malignant proliferation following the clonal expansion model.
Barrett’s esophagus, a columnar metaplasia of the lower esophagus epithelium related to gastroesophageal reflux disease, is the strongest known risk factor for the development of esophageal adenocarcinoma (EAC). Understanding the signal transduction events involved in esophageal epithelium carcinogenesis may provide insights into the origins of EAC and may suggest new therapies. To elucidate the molecular pathways of bile acid–induced tumorigenesis, the newly identified inflammation-associated signaling pathway involving I?B kinases ? (IKK?), tuberous sclerosis complex 1 (TSC1), and mammalian target of rapamycin (mTOR) downstream effector S6 kinase (S6K1) was confirmed to be activated in immortalized Barrett’s CPC-A and CPC-C cells and esophageal cancer SEG-1 and BE3 cells. Phosphorylation of TSC1 and S6K1 was induced in response to bile acid stimulation. Treatment of these cells with the mTOR inhibitor rapamycin or the IKK? inhibitor Bay 11-7082 suppressed bile acid–induced cell proliferation and anchorage-independent growth. We next used an orthotopic rat model to evaluate the role of bile acid in the progression of Barrett’s esophagus to EAC. Of interest, we found high expression of phosphorylated IKK? (pIKK?) and phosphorylated S6K1 (pS6K1) in tumor tissues and the Barrett’s epithelium compared with normal epithelium. Furthermore, immunostaining of clinical EAC tissue specimens revealed that pIKK? expression was strongly correlated with pS6K1 level. Together, these results show that bile acid can deregulate TSC1/mTOR through IKK? signaling, which may play a critical role in EAC progression. In addition, Bay 11-7082 and rapamycin may potentially be chemopreventive drugs against Barrett’s esophagus–associated EAC.
Yen, Chia-Jui; Izzo, Julie G.; Lee, Dung-Fang; Guha, Sushovan; Wei, Yongkun; Wu, Tsung-Teh; Chen, Chun-Te; Kuo, Hsu-Ping; Hsu, Jung-Mao; Sun, Hui-Lung; Chou, Chao-Kai; Buttar, Navtej S.; Wang, Kenneth K.; Huang, Peng; Ajani, Jaffer; Hung, Mien-Chie
The incidence of esophageal cancer is increasing. Worldwide it is the ninth most common malignancy and is endemic in many\\u000a parts of the world, particularly in the developing countries. There were 14,550 new cases and 13,770 deaths from esophageal\\u000a cancer in the United States in 2006. Esophageal cancer has two pathological subtypes: squamous cell carcinoma and adenocarcinoma.\\u000a Squamous cell carcinoma
Lana Y. Schumacher; Nicole B. Baril; Sherry M. Wren
After repair of esophageal atresia (EA) in a newborn, esophageal dysmotility presenting as dysphagia and symptomatic gastroesophageal reflux are common. Significant esophageal morbidity associated with EA extends into adulthood. In adulthood approximately one-fifth of the patients have developed epithelial metaplastic changes, one-third of these have intestinal metaplasia (Barrett esophagus). Surgical complications, increasing age, and impaired esophageal motility predict the development of epithelial metaplasia after repair of EA. To date, worldwide, eight cases of esophageal cancer have been reported in young adults treated for EA. Incidence of esophageal cancer after EA repair is very much likely to increase in the future. Life-long endoscopic follow-up is warranted in patients with EA. PMID:23737132
Rintala, R J; Pakarinen, M P
... literature OMIM Genetic disorder catalog Conditions > Esophageal atresia/tracheoesophageal fistula (often shortened to EA/TEF ) On this page: ... August 2012 What is EA/TEF? Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a condition resulting from abnormal ...
\\u000a Esophageal cancer is the fifth most common gastrointestinal cancer and the ninth leading cause of cancer death in the United\\u000a States. The incidence of esophageal adenocarcinoma is on the rise. Accurate staging of esophageal cancer is critical for the\\u000a selection of appropriate treatment. Endoscopic ultrasound (EUS) plays an important role in the staging of esophageal cancer.\\u000a EUS provides a detailed
Audrey H. Calderwood; Brian C. Jacobson
Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is the most common congenital anomaly of the esophagus. The improvement of survival observed over the previous two decades is multifactorial and largely attributable to advances in neonatal intensive care, neonatal anesthesia, ventilatory and nutritional support, antibiotics, early surgical intervention, surgical materials and techniques. Indeed, mortality is currently limited to those cases with coexisting severe life-threatening anomalies. The diagnosis of EA is most commonly made during the first 24 h of life but may occur either antenatally or may be delayed. The primary surgical correction for EA and TEF is the best option in the absence of severe malformations. There is no ideal replacement for the esophagus and the optimal surgical treatment for patients with long-gap EA is still controversial. The primary complications during the postoperative period are leak and stenosis of the anastomosis, gastro-esophageal reflux, esophageal dysmotility, fistula recurrence, respiratory disorders and deformities of the thoracic wall. Data regarding long-term outcomes and follow-ups are limited for patients following EA/TEF repair. The determination of the risk factors for the complicated evolution following EA/TEF repair may positively impact long-term prognoses. Much remains to be studied regarding this condition. This manuscript provides a literature review of the current knowledge regarding EA.
Pinheiro, Paulo Fernando Martins; Simoes e Silva, Ana Cristina; Pereira, Regina Maria
Barrett's esophagus (BE) is the premalignant lesion from which esophageal adenocarcinoma near the esophagogastric junction arises. The management of BE and the treatment of Barrett's esophageal adenocarcinoma (BEA) are important clinical issues in Europe and the United States. As the Helicobacter pylori infection rate in Japan is decreasing in the younger population, the incidence of BE and adenocarcinoma arising from BE may start increasing. Thus, we review the current status of BEA and its management. Magnifying endoscopy with narrow-band imaging is important for diagnosing dysplasia arising from BE. In Japan, adenocarcinoma arising from BE is managed the same way as squamous cell carcinoma in the same location. Strategies to prevent BEA may include medication such as non-steroidal anti-inflammatory drugs and proton pump inhibitors, and anti-reflux surgery. Understanding the pathophysiology of BE will help to reduce the incidence of BEA. PMID:23283352
Miyazaki, Tatsuya; Inose, Takanori; Tanaka, Naritaka; Yokobori, Takehiko; Suzuki, Shigemasa; Ozawa, Daigo; Sohda, Makoto; Nakajima, Masanobu; Fukuchi, Minoru; Kato, Hiroyuki; Kuwano, Hiroyuki
Esophageal atresia (EA) is a rare congenital malformation consisting of a lack of continuity between the upper and lower esophageal pouches, frequently associated with tracheoesophageal fistula. The prevalence of such rare abnormalities is established by global birth surveillance programs over the world. EUROCAT is a European program covering 1.7 million births since its creation. The prevalence of EA in Europe seems stable over decades. The National Birth Defects Prevention Network in the USA also shows a stable prevalence with a wide range between states or regions. In France, with the implementation of the national rare diseases plan, a reference center for congenital abnormalities of the esophagus was created in 2006 and a national registry for EA began patient inclusion in 2008. This has resulted in the establishment of the national live birth prevalence for EA, prenatal diagnosis rates, and clinical characteristics of EA patients, early survival, and early morbidity. Prevalence rates seem stable all over the world since many decades. Continuous surveillance of congenital abnormalities and specific registries are useful for epidemiologic data but also for public health authorities for helping families of rare diseases patients. PMID:23679022
Sfeir, R; Michaud, L; Salleron, J; Gottrand, F
Advanced esophageal carcinoma has poor prognosis with 5-year survival of less than 20%. This poor prognosis is the same for squamous cell carcinoma and adenocarcinoma. Surgical therapy, external radiation and chemotherapy with curative intent are usually impossible because of the advanced disease. Dysphagia is the most frequent symptom affecting quality of life. Bougies or balloon dilation improves dysphagia only short-term (few days). Nd-YAG laser, ACP and photodynamic therapy all have mid-range effect and require repetition after few weeks. Brachytherapy and esophageal self-expanding stent insertion have longer benefit. Stent insertion provides fastest improvement of dysphagia; however, complications in later setting occur in30% and require further endoscopic treatment. Brachytherapy has slower onset of benefit but has fewer complications and longer benefit. Brachytherapy is suitable for patients wit expected lifespan more than 3 months. Most important contraindication of brachytherapy is tracheo-esophageal fistula. PMID:19202963
Esophageal cancer (EsC) is one of the least studied and deadliest cancers worldwide because of its extremely aggressive nature and poor survival rate. It ranks sixth among all cancers in mortality. In retrospective studies of EsC, smoking, hot tea drinking, red meat consumption, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma. Barrett’s esophagus is clearly recognized as a risk factor for EsC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. Here, we investigated the epidemiologic patterns and causes of EsC. Using population based cancer data from the Surveillance, Epidemiology and End Results Program of the United States; we generated the most up-to-date stage distribution and 5-year relative survival by stage at diagnosis for 1998-2009. Special note should be given to the fact that esophageal cancer, mainly adenocarcinoma, is one of the very few cancers that is contributing to increasing death rates (20%) among males in the United States. To further explore the mechanism of development of EsC will hopefully decrease the incidence of EsC and improve outcomes.
We report a newborn with esophageal atresia (EA) in whom right tracheal bronchus (TB) and a tracheal diverticulum were identified intra-operatively. The right TB was further confirmed on MRI scan performed post-operatively. Such a tracheal trifurcation associated with EA has not been reported hitherto from Indian subcontinent.
Primary esophageal tuberculosis is virtually non-existent and there are few cases described of secondary esophageal tuberculosis. Esophageal tuberculosis should be suspected in patients with dysphagia, positive test results for tuberculin, active pulmonary disease or mediastinal adenopathies. Endoscopic or x-ray images could be indistinguishable from esophageal carcinomas, hence a diagnosis can prevent wrong treatments. Confirming the diagnosis requires isolation of tuberculosis bacillus. Treatment for a patient with esophageal tuberculosis is standard therapy. Key words: Tuberculosis, esophagus. PMID:16865167
Bańos, Ramón; Serrano, Andrés; Alberca, Fernando; Alajarín, María; Albaladejo, Aquilino; Vargas, Angel; Molina, Joaquín
Esophageal cancer is mainly found in Asia and east Africa and is one of the deadliest cancers in the world. However, it has not garnered much attention in the Western world due to its low incidence rate. An increasing amount of data indicate that esophageal cancer, particularly esophageal adenocarcinoma, has been rising by 6-fold annually and is now becoming the fastest growing cancer in the United States. This rise has been associated with the increase of the obese population, as abdominal fat puts extra pressure on the stomach and causes gastroesophageal reflux disease (GERD). Long standing GERD can induce esophagitis and metaplasia and, ultimately, leads to adenocarcinoma. Acid suppression has been the main strategy to treat GERD; however, it has not been proven to control esophageal malignancy effectively. In fact, its side effects have triggered multiple warnings from regulatory agencies. The high mortality and fast growth of esophageal cancer demand more vigorous efforts to look into its deeper mechanisms and come up with better therapeutic options.
Chai, Jianyuan; Jamal, M Mazen
In western industrialized countries, esophageal cancer is a rare entity. While smoking and alcohol are the major risk factors for squamous cell carcinoma, the most important etiological factor for adenocarcinoma is Barrett's esophagus caused by gastro-esophageal reflux. Over the past few decades there has been a dramatic increase in the incidence of adenocarcinoma. The prognosis for both types of esophageal cancer is poor, with a 5-year survival rate of < 10%. Only early stages have a good prognosis. While prevention of squamous cell carcinoma is limited to avoiding drinking and smoking, prevention of adenocarcinoma requires endoscopic surveillance of Barrett's esophagus and the treatment of any dysplasia arising in it. PMID:12198874
Rotthauwe, J; Lingenfelser, Th; Malfertheiner, P
A number of risk factors for esophageal and gastric cancers have emerged, yet little is known whether risk factors map to\\u000a molecular tumor markers such as overexpression of the tumor suppressor TP53. Using a US multicenter, population-based case–control study (170 cases of esophageal adenocarcinomas, 147 gastric cardia\\u000a adenocarcinomas, 220 non-cardia gastric adenocarcinomas, and 112 esophageal squamous cell carcinomas), we examined
Jonine D. Figueroa; Mary Beth Terry; Marilie D. Gammon; Thomas L. Vaughan; Harvey A. Risch; Fang-Fang Zhang; David E. Kleiner; William P. Bennett; Christine L. Howe; Robert Dubrow; Susan T. Mayne; Joseph F. Fraumeni Jr; Wong-Ho Chow
Undifferentiated large cell carcinoma is a rare entity in esophageal cancer and very few data are available in the literature on this uncommon histological subtype. We report a case of a 58-year-old Caucasian male previously treated with cisplatin/5-fluorouracil, docetaxel and carboplatin/plitidepsin who received treatment with a novel antitumor agent, Irvalec (PM02734), as fourth line. The patient received treatment from July 2006 to July 2009, a total of 49 cycles, at a dose of 2.4 mg/m2 as a 24-hour infusion every 3 weeks. He did not present severe complications or unplanned or cumulative toxicities. Complete and durable response according to RECIST was reported. He was alive at the last follow-up on March 2012.
Salazar, Ramon; Cuadra, Carmen; Gil-Martin, Marta; Vandermeeren, Andrea; Alfaro, Vicente; Coronado, Cinthya
Background: Incidence rates for adenocarcinomas of the esophagus and gastric cardia have risen steeply over the last few decades. To determine risk factors for these tumors, we conducted a multicenter, population-based, case-control study. Methods: The study included 554 subjects newly di- agnosed with esophageal or gastric cardia adenocarcinomas, 589 subjects newly diagnosed with esophageal squamous cell carcinoma or other gastric
Marilie D. Gammon; Janet B. Schoenberg; Habibul Ahsan; Harvey A. Risch; Thomas L. Vaughan; Wong-Ho Chow; Heidi Rotterdam; A. Brian West; Robert Dubrow; Janet L. Stanford; Susan T. Mayne; Diana C. Farrow; Shelley Niwa; William J. Blot; Joseph F. Fraumeni
We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×1010; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10?9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10?15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.
Abnet, Christian C; Freedman, Neal D; Hu, Nan; Wang, Zhaoming; Yu, Kai; Shu, Xiao-Ou; Yuan, Jian-Min; Zheng, Wei; Dawsey, Sanford M; Dong, Linda M; Lee, Maxwell P; Ding, Ti; Qiao, You-Lin; Gao, Yu-Tang; Koh, Woon-Puay; Xiang, Yong-Bing; Tang, Ze-Zhong; Fan, Jin-Hu; Wang, Chaoyu; Wheeler, William; Gail, Mitchell H; Yeager, Meredith; Yuenger, Jeff; Hutchinson, Amy; Jacobs, Kevin B; Giffen, Carol A; Burdett, Laurie; Fraumeni, Joseph F; Tucker, Margaret A; Chow, Wong-Ho; Goldstein, Alisa M; Chanock, Stephen J; Taylor, Philip R
Background. The pathogenesis of esophageal atresia and tracheoesophageal fistula (EA\\/TEF) remains unknown. We have found previously that an initial esophageal atresia, followed by an abnormal (absent) branching pattern of the middle branch of a trifurcation of the lung\\/tracheal bud, leads to the neonatal finding of TEF. Mice null mutant for hedgehog signaling can experience the development of EA\\/TEF, but the
Troy L. Spilde; Amina M. Bhatia; Sheilendra Mehta; Daniel J. Ostlie; Mark J. Hembree; Barry L. Preuett; Krishna Prasadan; Zhixing Li; Charles L. Snyder; George K. Gittes
Epidermal growth factor receptor, phosphatidylinositol-3-kinase catalytic subunit/PTEN, and KRAS/NRAS/BRAF in primary resected esophageal adenocarcinomas: loss of PTEN is associated with worse clinical outcome.
Alterations of the epidermal growth factor receptor (EGFR) can be observed in a significant subset of esophageal adenocarcinomas (EACs), and targeted therapy against EGFR may become an interesting approach for the treatment of these tumors. Mutations of KRAS, NRAS, BRAF, and phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and deregulation of PTEN expression influence the responsiveness against anti-EGFR therapy in colorectal carcinomas. We investigated the prevalence of these events in a collection of 117 primary resected EACs, correlated the findings with EGFR expression and amplification, and determined their clinicopathologic impact. KRAS mutations were detected in 4 (3%) of 117 tumors (3× G12D and 1 G12V mutation). One tumor had a PIK3CA E545K mutation. Neither NRAS nor BRAF mutations were detected. Sixteen (14%) of 117 cases were negative for PTEN expression, determined by immunohistochemistry. Loss of PTEN was observed predominantly in advanced tumor stages (P = .004). There was no association between PTEN and EGFR status. Loss of PTEN was associated with shorter overall and disease-free survival (P < .001 each) and also an independent prognostic factor in multivariate analysis (P = .015). EGFR status had no prognostic impact in this case collection. In summary, loss of PTEN can be detected in a significant subset of EAC and is associated with an aggressive phenotype. Therefore, PTEN may be useful as a prognostic biomarker. In contrast, mutations of RAS/RAF/PIK3CA appear only very rarely, if at all, in EAC. A possible predictive role of PTEN in anti-EGFR treatment warrants further investigations, whereas determination of RAS/RAF/PIK3CA mutations may only have a minor impact in this context. PMID:23158210
Bettstetter, Marcus; Berezowska, Sabina; Keller, Gisela; Walch, Axel; Feuchtinger, Annette; Slotta-Huspenina, Julia; Feith, Marcus; Drecoll, Enken; Höfler, Heinz; Langer, Rupert
The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma.
An A to G transition at the 181 base pair position upstream of the transcription initiation site of the matrix metalloproteinase-7 (MMP-7) gene (-181A/G) may modify the development and progression of some diseases via influencing the transcription activity of the promoter. To assess the effects of the functional single nucleotide polymorphism on cancer susceptibility and progression, the MMP-7 -181A/G genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis among 258 patients with esophageal squamous cell carcinoma (ESCC), 201 patients with gastric cardiac carcinoma (GCA), 243 patients with non-small cell lung carcinoma (NSCLC) and 350 healthy individuals without cancer. The result showed that the frequency of the -181G allele in ESCC, GCA and NSCLC patients was significantly higher than that in healthy controls (P = 0.019, 0.023 and 0.004, respectively). Compared with the A/A genotype, genotypes with the -181G allele (A/G + G/G) significantly increased susceptibility to all three tumors, with adjusted odds ratio of 1.83 (95% CI = 1.12-2.99) for ESCC, 1.96 (95% CI = 1.17-3.29) for GCA and 2.00 (95% CI = 1.23-3.24) for NSCLC. Stratification analysis showed that smoking did not significantly influence the association between the MMP-7-181A/G and GCA or NSCLC, while the -181G allele only significantly increased susceptibility to ESCC among smokers. In addition, association between the -181G allele and susceptibility to ESCC and GCA showed significance only among individuals with family history of upper gastrointestinal cancer. The correlation of the MMP-7-181A/G polymorphism with potential of lymphatic metastasis was not observed in all three tumors. The study suggested that, the MMP-7-181A/G polymorphism might be a candidate marker for predicting individuals who are at higher risk to certain tumors but might not be used to predict potential of lymphatic metastasis in ESCC, GCA and NSCLC. PMID:15930031
Zhang, Jianhui; Jin, Xia; Fang, Shumei; Wang, Rui; Li, Yan; Wang, Na; Guo, Wei; Wang, Yimin; Wen, Denggui; Wei, Lizhen; Dong, Zhiming; Kuang, Gang
Four patients with herpetic esophagitis were examined. In three of them, the presenting symptom was odynophagia. Early in the course of herpetic esophagitis, shallow round and oval ulcers were seen on barium esophagograms. Later, the ulcers filled with fibrinous exudate, forming nodular plaques that projected into the esophageal lumen. Although these findings are diagnostic of esophagitis, they are not specific for a herpes virus infection. The definitive diagnosis must be established by histologic examination, which demonstrates the cytopathic effect of the herpes virus infection within the squamous epithelium.
Shortsleeve, M.J.; Gauvin, G.P.; Gardner, R.C.; Greenberg, M.S.
Background\\/Purpose: The purpose of this analysis was to investigate outcomes in newborns with esophageal atresia (EA) or tracheoesophageal fistula (TEF) with respect to prognostic classifications and complications.Methods: Charts of all 144 infants with EA\\/TEF treated at British Columbia Children’s Hospital (BCCH) from 1984 to 2000 were reviewed. Patient demographics, frequency of associated anomalies, and details of management and outcomes were
David E Konkin; Wael A O’Hali; Eric M Webber; Geoffrey K Blair
The development of achalasia in a patient with a history of esophageal atresia (EA) is rare. Here, we report a patient who had undergone surgery for EA at birth and presented achalasia at 30?years of age. He was successfully treated with laparoscopic surgery. PMID:22151015
Marinello, F G; Targarona, E M; Poca, M; Mones, J; Hernández-Ballesteros, C
PurposeEsophageal atresia (EA) with tracheoesophageal fistula (TEF) type C accounts for 85% of all EA. In our center, patients were previously started on total parenteral nutrition (TPN) postoperatively and oral feedings initiated only after a contrast esophagogram. Our aim is to assess the benefit of intraoperatively placed transanastomotic feeding tubes (TAFTs).
Saleh I. Alabbad; Jon Ryckman; Pramod Shailendra Puligandla; Kenneth Shaw; Luong T. Nguyen; Jean-Martin Laberge
Accumulating epidemiological studies have supported the link between increased body mass index, central obesity and esophageal adenocarcinoma. This association appears stronger than that for other types of obesity-related cancers. Central obesity or visceral fat, more often observed in men, is much more strongly associated with adenocarcinoma than body mass index alone, possibly contributing to the imbalance of disease occurrence between the sexes. Potential mechanisms underlying the association between obesity and esophageal adenocarcinoma have been recently identified, including the insulin-like growth factor pathway, adipokines and sex hormone disturbances. These findings are summarized in this review; however, more research is warranted before these mechanisms are conclusively established.
Chen, Qi; Zhuang, Hengguo
Background & Aims: Barrett's esophagus (BE) results from chronic, severe gastroesophageal reflux and predisposes to esophageal adenocarcinoma. Cyclooxygenase (COX)-2 is involved in chronic inflammation and epithelial cell growth. We investigated COX-2 expression in BE and esophageal adenocarcinoma to explore a potential relation between COX-2 expression and metaplasia or carcinogenesis. Methods: Endoscopic mucosal biopsy specimens of Barrett's intestinal metaplasia (n =
Vivian N. Shirvani; Rodica Ouatu-Lascar; Baljeet S. Kaur; M. Bishr Omary; George Triadafilopoulos
Twelve patients with known esophageal varices and willingness to cooperate were included in the study. Medications administered were placebo, 2 mg of glucagon, and 30 mg of propantheline bromide. All medications were given double-blind and crossover. On the basis of this study the authors believe that for optimal visualization of esophageal varices the following is the procedure of choice: (I)
EDWARD M. COCKERILL; ROSCOE E. MILLER; STANLEY M. CHERNISH; GORDON C. McLAUGHLIN; BRUCE E. RODDA
Evaluation of gap length is an important part of preoperative assessment of esophageal atresia (EA) without distal tracheoesophageal fistula. A technique of measuring the esophageal gap in isolated EA using carbon dioxide gas insufflation of the stomach through a port and a laparoscope is described. PMID:23292535
This book contains the proceedings on esophageal cancer. Topics covered include: Scope of the problem, Diagnostic considerations: Methods of early diagnosis, Staging criteria, Elective surgical management, and Postoperative complications.
Delarue, N.C. (Univ. of Toronto, Toronto (CA)); Wilkins, E.W. Jr. (Harvard Medical School, MA (US)); Wong, J. (Dept. of Surgery, Univ. of Hong Kong (HK))
Eosinophilic esophagitis is a chronic inflammatory disorder characterized by dense eosinophilic infiltration of the esophageal\\u000a mucosa. The pathogenesis is incompletely understood and food allergies and aeroallergens have been implicated. The most common\\u000a clinical presentation in adults is dysphagia to solids. Its associated endoscopic findings are distinct and include concentric\\u000a rings and longitudinal furrows, although endoscopy may be unremarkable in a
Fouad J. Moawad; Ganesh R. Veerappan; Roy K. Wong
Despite progress in the management of esophageal perforations by early diagnosis, antibiotics, monitoring, and respiratory and nutritional support, it still remains as a disasterous condition. The most common cause of esophageal perforation is iatrogenic disruption. The result in the management of esophageal perforation is influenced by several factors: localization and size of the rupture, length of delay in diagnosis, age, extent of mediastinal and pleural contamination, the presence of underlying esophageal diseases, and inflammation or tumor at the perforation localization. In this study, 7 cases of esophageal perforations in the last six years have been analysed retrospectively. In study group, there were 5 males and 2 females, and the mean age was 36 (12-75). The most common cause of perforation was gunshot injury (3 cases), and stab wound (1 case), foreign body (1 case), iatrogenic distruption (2 cases). Three patients died and four patients were discharged from hospital with recovery. Esophageal perforation is a life-threatening condition. Early diagnosis and repair reduces the morbidity and mortality. PMID:11705168
Ertekin, C; Yanar, H T; Gülo?lu, R; Tavilo?lu, K; Dilege, S
Intragastric pressure measurements and cineradiographic contrast studies were done in monkeys in order to determine the pressure at which esophageal reflux occurred. Antireflux operative procedures were performed above and below the diaphragm, and the results compared. The Nissen fundoplication proved to be the most effective type of mechanical antireflux valve and worked equally well placed above and below the diaphragm. Of 200 consecutive adult patients undergoing operative correction of esophageal reflux, 19 had severe esophageal strictures. Through a transthoracic approach, two patients had subdiaphragmatic Nissen fundoplications, one with adenocarcinoma of the esophagus had an esophageal resection, and 16 had supradiaphragmatic Nissen fundoplications; those 16 patients form the basis of this report. No patients died; superficial, temporary esophageal ulcerations developed in two. Follow-up times have ranged from six months to eight years; the results in all cases have been good. Experimental and clinical evidence supports the belief that this less radical approach is the treatment of choice in the management of severe esophageal strictures secondary to reflux esophagitis. Images Fig. 1. Fig. 2. Figs. 3. and 4. Figs. 5-7. Figs. 8. and 9. Fig. 10. Figs. 11. and 12.
Pennell, T C
Background/Aim: Thrombocytosis is found to be associated with unfavorable prognosis in esophageal carcinoma. Platelets produce thymidine phosphorylase which is a platelet-derived endothelial cell growth factor with angiogenic activity. Increased platelet count may be translated into enhanced tumor growth. We examined the relation between platelet count and several prognostic variables in patients with esophageal cancer. Patients and Methods: Three hundred and eighty-one cases with esophageal cancer that underwent esophagectomy in a referral cancer institute during a 5-year period were studied retrospectively. The relation between preoperative platelet count and patient age, gender, site of tumor, presence of multiple cancers and clinicopathological characteristics including histological type, tumor size, depth of penetration (T), lymph node involvement (N), distant metastasis (M), degree of differentiation, presence of vascular, lymphatic and perineural invasion was examined. Results: Squamous cell carcinoma (SCC) constituted 93% and adenocarcinoma 7% of cases. Most of patients were in stage III, followed by stage II. The mean platelet count was 245±76 (× 109 /L). There was no statistically significant correlation between platelet counts with prognostic factors except a weak linear correlation between platelet count and and tumor size (P= 0.03, Pearson correlation coefficient: 0.16). Patients with adenocarcinoma had a higher platelet count than those with SCC (P= 0.003). Conclusion: Platelet count does not correlate with prognostic factors in esophageal cancer. However, it is significantly different between SCC and adenocarcinoma of esophagus.
Aminian, Ali; Karimian, Faramarz; Mirsharifi, Rasoul; Alibakhshi, Abbas; Dashti, Habibollah; Jahangiri, Yosra; Safari, Saeed; Ghaderi, Hamid; Noaparast, Morteza; Hasani, Sharareh M.; Mirsharifi, Alireza
Esophageal cancers are highly malignant tumours with often a poor prognostic, except for minimal lesions treated with surgery. Radiation therapy, or combined radiation and chemotherapy is the most used therapeutic modality, alone or before oesophagectomy. The delineation of target volumes is now more accurate owing the possibility to use routinely the new imaging techniques (mainly PET). The aim of this work is to precise the radio-anatomical particularities, the pattern of spread of esophageal cancer and the principles of 3D conformal radiotherapy illustrated with a clinical case. PMID:21129673
Dupuis, O; Ganem, G; Béra, G; Pointreau, Y; Pradier, O; Martin, P; Mirabel, X; Denis, F
Eosinophilic esophagitis is a chronic inflammatory disorder characterized by dense eosinophilic infiltration of the esophageal mucosa. The pathogenesis is incompletely understood and food allergies and aeroallergens have been implicated. The most common clinical presentation in adults is dysphagia to solids. Its associated endoscopic findings are distinct and include concentric rings and longitudinal furrows, although endoscopy may be unremarkable in a minority of patients. A number of management strategies exist; however, data are limited in adults, and only a few are based on randomized controlled trials. Management options include dietary modifications, pharmacological therapy, and endoscopic dilation. PMID:19554448
Moawad, Fouad J; Veerappan, Ganesh R; Wong, Roy K
Congenital esophageal atresia (EA) and\\/or tracheoesophageal fistula (TEF) are common congen- ital anomalies. Respiratory and GI complications occur frequently, and may persist lifelong. Late complications of EA\\/TEF include tracheomalacia, a recurrence of the TEF, esophageal stricture, and gastroesophageal reflux. These complications may lead to a brassy or honking-type cough, dysphagia, recurrent pneumonia, obstructive and restrictive ventilatory defects, and airway hyperreactivity.
Thomas Kovesi; Steven Rubin
Background: For reasons yet unknown, the incidence of esophageal and gastric cardia adenocarcinoma is increasing rapidly and moderately, respectively. These tumors occur predominantly among males. We hypothesized that stressful psychosocial working conditions might be involved in the etiology of these cancers. Objective: To study if job strain, work pace satisfaction and coping are linked to the risk of esophageal or
Catarina Jansson; Anna L. V. Johansson; Kerstin Jeding; Paul W. Dickman; Olof Nyrén; Jesper Lagergren
Esophageal strictures remain the most frequent complication after esophageal atresia (EA) repair despite refinements in operative techniques. With an incidence of anastomotic stricture between 8% and 49%, EA is the most frequent cause of benign esophageal stricture in children. The mainstay of treatment for esophageal stricture is dilatation with a 58-96% success rate. In order to relieve dysphagia, between 1 and 15 dilatations will be required in each EA patient with an esophageal stricture. However dilatations may lead to complications including perforation (0.1-0.4% of all esophageal benign strictures) and sociopsychological morbidity. Fifty percent of EA strictures will improve in 6 months. However, 30% will persist and require repeat dilatations. The present article explores the variety of non-surgical alternative treatments for anastomotic strictures after EA repair, focusing on triamcinolone acetonide, mitomycin C and esophageal stents. We propose an algorithm for a more standardized therapeutic approach, with the hope that an international panel of experts could meet and establish a consensus. PMID:23679028
Lévesque, D; Baird, R; Laberge, J-M
A protocol is suggested of complex diagnosis and treatment of Barrett's esophagus using sparing endoscopic removal of Barrett's epithelium in combination with surgery and medicinal antireflux therapy. Eighty-three patients were diagnosed and treated for hernia of esophageal foramen of the diaphragm and gastro-esophageal reflux complicated by Barrett's esophagus. Ninety-two percent of patients receiving our four-component treatment were cured; no recurrent esophageal adenocarcinoma was reported during the 56.7 +/- 2.4 month follow-up. Conversely, in patients receiving three-component treatment, efficacy was 56%; esophageal adenocarcinoma was reported in 3 (12%). PMID:20210013
Burmistrov, M V; Ivanov, A I; Petrov, S V; Akhmetov, T R; Sigal, E I; Murav'ev, V Iu; Moroshek, A A; Broder, I A
Introduction Esophageal cancer remains a challenging clinical problem, with overall long-term survivorship consistently at a level of approximately\\u000a 30%. The incidence of esophageal cancer is increasing worldwide, with the most dramatic increase being seen with respect to\\u000a esophageal adenocarcinoma.\\u000a \\u000a \\u000a \\u000a \\u000a Discussion Pretreatment staging accuracy has improved with the utilization of CT and PET scans, as well as endoscopic ultrasound and\\u000a endoscopic mucosal resection.
Donald E. Low
Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis of many solid malignancies. The influence of angiogenesis and VEGF expression on progression and recurrence of esophageal cancer has been investigated over the last years. This article reviews the prognostic significance of VEGF expression, microvessel density (MVD), and lymphangiogenic factors in squamous cell carcinoma (SCC), Barrett's dysplasia, and adenocarcinoma (AC) of the esophagus, their predictive value for treatment response to chemo-radiotherapy and new anti-angiogenic treatment strategies. PMID:15282704
Kleespies, Axel; Guba, Markus; Jauch, Karl-Walter; Bruns, Christiane J
Background: Many patients who have esophageal atresia and tracheoesophageal fistula (EA-TEF) have associated tracheomalacia, which is though to be one of the reasons for respiratory complications after surgical correction of the abnormality.Methods: In this study, tracheas from Adriamycin-induced EA-TEF fetal rats were examined histologically and relevant cross-sectional parameters of the tracheas were measured.Results: The tracheal lumen in tracheomalacia was small
Bao Quan Qi; Jamal Merei; Pam Farmer; Suzanne Hasthorpe; John M Hutson; Nate A Myers; Spencer W Beasley
Background\\/Purpose: The organogenesis of esophageal atresia with tracheoesophageal fistula (EA-TEF) is unknown. Using an established model for EA-TEF in rats, the authors proposed to study this aberrancy of development in the hope of gaining insight into its mechanism of formation.Methods: Pregnant Sprague-Dawley rats were injected with 2.2 mg\\/kg of Adriamycin intraperitoneally on days 6 through 9 of gestation. Using microdissection,
Christopher A Crisera; Patrick R Connelly; Alexander R Marmureanu; Kari L Colen; Michael I Rose; Min Li; Michael T Longaker; George K Gittes
Esophageal atresia and tracheoesophageal fistula (EA\\/TEF) are major congenital malformations affecting 1:3500 live births.\\u000a Current research efforts are focused on understanding the etiology of these defects. We describe well-known animal models,\\u000a human syndromes, and associations involving EA\\/TEF, indicating its etiologically heterogeneous nature. Recent advances in\\u000a genotyping technology and in knowledge of human genetic variation will improve clinical counseling on etiologic
Elisabeth M. de Jong; Janine F. Felix; Annelies de Klein; Dick Tibboel
Background\\/purposeFor children with esophageal atresia (EA) or tracheoesophageal fistula (TEF), the first years of life can be associated with many problems. Little is known about the long-term function of children who underwent repair as neonates. This study evaluates outcome and late sequelae of children with EA\\/TEF.
D. C Little; F. J Rescorla; J. L Grosfeld; K. W West; L. R Scherer; S. A Engum
The management of esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) has undergone many changes. As a result of recent advances in neonatal intensive care and pediatric anesthesia, the survival of infants with EA and TEF has improved markedly, but the occurrence of anastomosic complications has remained constant. To overcome this problem, various techniques and suture materials have been
A. H. Al-Salem; S. Qaisaruddin; H. Abu Srair; I. Al Dabbous; R. Al-Hayek
Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease. Despite the increasing diagnosis of EoE globally, the causes of EoE and other esophageal eosinophilic disorders are not clearly understood. EoE pathology includes accumulation of inflammatory cells (e.g., eosinophils, mast cells), characteristic endoscopic features (e.g., furrows, the formation of fine concentric mucosal rings, exudates), and functional impairments (e.g., esophageal stricture, dysmotility). We hypothesized that the esophageal structural pathology and functional impairments of EoE develop as a consequence of the effector functions of the accumulated inflammatory cells. We analyzed eosinophils (anti-major basic protein immunostaining), esophageal stricture (X-ray barium swallowing), and esophageal motility (isometric force) in two established transgenic murine models of EoE (CD2-IL-5 and rtTA-CC10-IL-13) and a novel eosinophil-deficient model (?dblGATA/CD2-IL-5). Herein, we show the following: 1) CD2-IL-5 and doxycycline (DOX)-induced rtTA-CC10-IL-13 mice have chronic eosinophilic and mast cell esophageal inflammation; 2) eosinophilic esophageal inflammation promotes esophageal stricture in both transgenic murine models; 3) the eosinophil-deficient ?dblGATA/CD-2-IL-5 mice were protected from the induction of stricture, whereas the eosinophil-competent CD2-IL-5 mice develop esophageal stricture; 4) esophageal stricture is not reversible in DOX-induced rtTA-CC10-IL-13 mice (8 wk DOX followed by 8 wk no-DOX); and 5) IL-5 transgene-induced (CD2-IL-5) EoE evidences esophageal dysmotility (relaxation and contraction) that is independent of the eosinophilic esophageal inflammation: CD2-IL-5 and ?dblGATA/CD2-IL-5 mice have comparable esophageal dysmotility. Collectively, our present study directly implicates chronic eosinophilic inflammation in the development of the esophageal structural impairments of experimental EoE.
Mavi, Parm; Rajavelu, Priya; Rayapudi, Madhavi; Paul, Richard J.
Purpose: The purpose of this study was to determine whether aortic arch anomalies are associated with long gap esophageal atresia and tracheoesophageal fistula (EA-TEF).Methods: The authors performed a retrospective review of all infants who had EA-TEF from 1980 to 1996 at two pediatric surgery centers. Two hundred three infants who had EA-TEF were identified.Results: Twelve infants were noted to have
T. G Canty; E. M Boyle; B Linden; P. J Healey; D Tapper; D. G Hall; R. S Sawin; J. E Foker
\\u000a Purpose: To present the results of a prospective phase II study in esophageal carcinoma.\\u000a \\u000a \\u000a \\u000a Patients and Methods: Patients received single doses of 1.8 Gy up to 27 Gy, then concomitant boost to a total of 50.4 Gy (PTV2 [planning target\\u000a volume], single dose 1.8 Gy) and 64.8 Gy (PTV1, single dose 1.2 Gy in the morning and 1.8 Gy in the afternoon)
Thomas B. Brunner; Andreas Rupp; Winfrid Melzner; Gerhard G. Grabenbauer; Rolf Sauer
We present a retrospective evaluation of our experience in the period that goes from January 1992 to December 1998, clinical records of 58 patients ages from 2 months old to 15 years, male and female, who were treated at the GI service of Instituto de Salud del Ni o, were reviewed. All of them had esophageal stenosis and were included in the Esophageal Dilatation Program with Savary-Gilliard bougies. The causes of Esophageal Stenosis in the study were: Caustic agents 37.9%, gastro esophageal reflux (GER) 20.7%, surgery sequela 19.0%, related to esophageal esclerotherapy 12.1%, foreign body itself or maneuvers to retrieve them 8.6%, stomach adenocarcinoma invading the esophagus. Patients were classified in three groups: Group 1: stenosis due to caustic agents Group 2: stenosis due to GER Group 3: The remaining causes mentioned above., In each the following was calculated: the arithmetical media, the range of dilatations sessions and the total number of them. The higher figures took place in group 1. So we conclude that the number of sessions is directly related with the cause of the stenosis, requiring more number of dilatations to get a better response. Finally the response to treatment is evaluated considering a good response in 72.4%. A mild response in 15.5% and therapeutic failure in 12.1% of patients. The rate of complications was 10.3 per patient and 1.1 in relation to the total number of dilatation sessions. The main complications were: gastric perforation, duodenal perforation, pneumomediastinum, esophago-tracheal fistulae andi pseudodiverticulum formation, with resolution as seen in posterior controls. These complications occured after the proceeding took place. The treatment was installed according to each case. The patients with duodenal perforation died. We conclude that esophageal dilatations in infants with esophageal stenosis, of different ethiology, are secure and efficient. PMID:12181577
Alarcón, Anibal; Talavera, Godofredo; Gonzales, Jóse; Rivera, Juan
Metastases of esophageal carcinoma to the skeletal muscle are rare, but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT). A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases. Four patients had skeletal muscle metastases of esophageal carcinoma, including two patients with squamous cell carcinoma. In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases, muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma. In all cases, skeletal muscle metastases were the first manifestation of systemic disease. In three patients palliation was obtained with the combination of external beam radiation therapy, systemic chemotherapy or surgical resection. Skeletal muscle metastases are a rare complication of esophageal carcinoma. PMID:23002370
Cincibuch, Jan; Myslive?ek, Miroslav; Melichar, Bohuslav; Neoral, Cestmír; Metelková, Iva; Zezulová, Michaela; Procházková-Študentová, Hana; Flodr, Patrik; Zlevorová, Miloslava; Aujeský, René; Cwiertka, Karel
A more detailed understanding of the somatic genetic events that drive gastrointestinal adenocarcinomas is necessary to improve diagnosis and therapy. Using data from high-density genomic profiling arrays, we conducted an analysis of somatic copy-number aberrations (SCNAs) in 486 gastrointestinal adenocarcinomas including 296 esophageal and gastric cancers. Focal amplifications were substantially more prevalent in gastric/esophageal adenocarcinomas than colorectal tumors. We identified 64 regions of significant recurrent amplification and deletion, some shared and others unique to the adenocarcinoma types examined. Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential utility of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared to colorectal cancers. Amplified loci implicated genes with known involvement in carcinogenesis but also pointed to regions harboring potentially novel cancer genes, including a recurrent deletion found in 15% of esophageal tumors where the Runt transcription factor subunit RUNX1 was implicated, including by functional experiments in tissue culture. Together, our results defined genomic features that were common and distinct to various gut-derived adenocarcinomas, potentially informing novel opportunities for targeted therapeutic interventions.
Dulak, Austin M; Schumacher, Steve; van Lieshout, Jasper; Imamura, Yu; Fox, Cameron; Shim, Byoungyong; Ramos, Alex; Saksena, Gordon; Baca, Sylvan; Baselga, Jose; Tabernero, Josep; Barretina, Jordi; Enzinger, Peter; Corso, Giovanni; Roviello, Franco; Lin, Lin; Bandla, Santhoshi; Luketich, James; Pennathur, Arjun; Meyerson, Matthew; Ogino, Shuji; Shivdasani, Ramesh A; Beer, David G; Godfrey, Tony E; Beroukhim, Rameen; Bass, Adam J
A more detailed understanding of the somatic genetic events that drive gastrointestinal adenocarcinomas is necessary to improve diagnosis and therapy. Using data from high-density genomic profiling arrays, we conducted an analysis of somatic copy-number aberrations in 486 gastrointestinal adenocarcinomas including 296 esophageal and gastric cancers. Focal amplifications were substantially more prevalent in gastric/esophageal adenocarcinomas than colorectal tumors. We identified 64 regions of significant recurrent amplification and deletion, some shared and others unique to the adenocarcinoma types examined. Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared with colorectal cancers. Amplified loci implicated genes with known involvement in carcinogenesis but also pointed to regions harboring potentially novel cancer genes, including a recurrent deletion found in 15% of esophageal tumors where the Runt transcription factor subunit RUNX1 was implicated, including by functional experiments in tissue culture. Together, our results defined genomic features that were common and distinct to various gut-derived adenocarcinomas, potentially informing novel opportunities for targeted therapeutic interventions. PMID:22751462
Dulak, Austin M; Schumacher, Steven E; van Lieshout, Jasper; Imamura, Yu; Fox, Cameron; Shim, Byoungyong; Ramos, Alex H; Saksena, Gordon; Baca, Sylvan C; Baselga, Jose; Tabernero, Josep; Barretina, Jordi; Enzinger, Peter C; Corso, Giovanni; Roviello, Franco; Lin, Lin; Bandla, Santhoshi; Luketich, James D; Pennathur, Arjun; Meyerson, Matthew; Ogino, Shuji; Shivdasani, Ramesh A; Beer, David G; Godfrey, Tony E; Beroukhim, Rameen; Bass, Adam J
Esophageal cancer mortality rates in Central and Eastern Europe have been increasing steadily and are expected to increase further in the future. To evaluate the role of risk factors for esophageal cancer in this population, a multicenter study was conducted, with investigation of tobacco and alcohol as one of the principal aims. We have included 192 squamous cell carcinoma (SCC) and 35 adenocarcinoma cases of the esophagus diagnosed at designated hospitals in 5 centers from Romania, Russia, the Czech Republic and Poland. Controls were frequency matched from patients in the same hospital as the cases (n=1,114). Our results showed that the risk of esophageal SCC may be increased by approximately 7-fold for current smokers (OR=7.41, 95% CI 3.98-13.79) and by 3-fold for ever alcohol drinkers (OR=2.86, 95% CI 1.06-7.74). Dose-response relations were evident for both the frequency and duration of tobacco and of alcohol on the risk of esophageal SCC. Risk estimates for tobacco smoking were highest for lower esophageal SCCs, while risk estimates for alcohol drinking were highest for upper esophageal SCCs; though differences were not statistically significant. For adenocarcinoma of the esophagus, our results suggested a more modest increase in risk because of tobacco smoking than that for SCC of the esophagus and no association with alcohol consumption, although our sample size was small. A synergistic interaction between tobacco and alcohol was observed for the risk of esophageal SCC, highlighting the importance of both factors for esophageal cancers in Central and Eastern Europe. PMID:17205526
Hashibe, Mia; Boffetta, Paolo; Janout, Vladimir; Zaridze, David; Shangina, Oxana; Mates, Dana; Szeszenia-Dabrowska, Neonila; Bencko, Vladimir; Brennan, Paul
Recently, the guidelines for the treatment of gastroesophageal reflux disease (GERD) by the Japanese Society of Gastroenterology. There are many statements including recommended grade (from A to D) and evidence level (from I to VI) for the epidemiology, pathogenesis, diagnosis, medical treatments, surgical treatment of GERD, reflux esophagitis after gastrectomy, and non-typical symptoms of GERD. In this manuscript, we showed the latest date and current status of GERD in Japan used this guidelines. In summary, the prevalence of GERD has been increasing since the end of 1990s, the 1st choice of medical treatment is proton pump inhibitors, endoscopic treatments for GERD are not available in Japan, laparoscopic Toupet fundoplication is superior to laparoscopic Nissen fundoplication as postoperative dysphagia with similar reflux control, and complications of surgical treatment are pneumothorax, splenic injury, aortic injury, gastric ulcer, sever dysphagia, gastric perforation etc., but complication rate is low. PMID:21916192
Omura, Nobuo; Kashiwagi, Hideyuki
Traditionally, open repair of esophageal atresia (EA) with tracheoesophageal fistula (TEF) required thoracotomy. Innovations in minimal access surgery have created a thoracoscopic technique resulting in violation of the pleural space. Most pediatric surgeons favor an extrapleural approach for open repair. We present a novel minimal access, extrapleural technique for repairing EA with TEF. A 2-day-old infant with EA and distal TEF underwent thoracoscopic extrapleural repair that utilized three ports. Initial creation of the extrapleural space was achieved through one of the port sites and was completed thoracoscopically. A thoracoscopic repair of EA with distal TEF was achieved within the extrapleural space. A small tear in the pleura was inadvertently created during the dissection. The child began feeding normally. At 1 year of age, the patient had dysphagia requiring a single esophageal dilatation. This is the first known report of an extrapleural thoracoscopic repair of EA with TEF. Although thoracoscopic repairs of EA/TEF have been previously reported, these were all done transpleurally. Many pediatric surgeons favor the extrapleural approach for two reasons: (1) containment of a potential leak within the extrapleural space, avoiding an empyema, and (2) easier transpleural access for future thoracic procedures. PMID:15789240
Tsao, Kuojen; Lee, Hanmin
A 55-year-old heart transplant recipient with reflux esophagitis presented for routine endoscopic surveillance of an area of Barrett's metaplasia initially seen 3 years previously. Esophagogastroduodenoscopy revealed adenocarcinoma at 33 cm from the incisors. The preoperative clinical stage was T1N0M0 by endoscopic ultrasound. Transhiatal esophagectomy was performed with R0 resection of the cancer, and the patient recovered uneventfully. Pathologic examination confirmed esophageal adenocarcinoma (T1N0M0) in Barrett's mucosa. The patient is doing well, and has no evidence of disease after 18 months. PMID:15276556
Gupta, Dipin; Macha, Mahender; Piacentino, Valentino; Singhal, Arun K; Sasken, Harvey F; Furukawa, Satoshi; Dempsey, Daniel T
Opinion statement Esophageal dilation is the treatment of choice for most patients with esophageal dysphagia (functional and mechanical). Multiple\\u000a forms of esophageal dilators are available. Mechanical dilators (guidewire\\/nonguidewire assisted) are the major forms of dilators\\u000a used. Balloon dilator use has increased but they offer only a marginal advantage over traditional mechanical dilators at a\\u000a greatly increased cost (2° to single use).
Timothy T. Nostrant
In order to asses whether in reflux esophagitis morphological and functional disorders persist after macroscopic healing, cimetidine was given for 6–12 weeks at a dose of 1.6 g\\/day to 30 patients with acid gastroesophageal reflux and esophagitis. The mucosal defects healed in 6 patients, improved in 14 patients, and remained unchanged in 10 patients. Lower esophageal sphincter pressure, acid clearance,
Amnon Sonnenberg; Gerd Lepsien; STEFAN A. MISILLER-LISSNER; Hans R. Koelz; J. Rüdiger Siewert; André L. Blum
The fasting lower esophageal sphincter pressure of 18 normal volunteers was compared to 22 patients with symptoms and objective evidence of gastroesophageal reflux. Lower esophageal sphincter pressure was measured by rapid pull-through using an 8-lumen radially perfused catheter that sampled pressure every45 degrees around the circumference of the sphincter. The 22 reflux patients were subdivided for analysis into two groups, those with an acute inflammatory infiltrate on biopsy and those without inflammation. Those patients without inflammatory esophagitis had normal sphincter pressures. Those with a definite inflammatory infiltrate had pressures significantly less than normal. The least reliable separation between normals and those with inflammatory esophagitis occurred in the anterior orientations. We conclude that while basal lower esophageal sphincter pressure measurement may identify patients with reflux and inflammatory esophagitis, it is of no help in identifying those patients with reflux unassociated with inflammation. Decreased basal fasting LESP does not appear to be the most important primary determinant of gastroesophageal reflux. PMID:7379675
Welch, R W; Luckmann, K; Ricks, P; Drake, S T; Bannayan, G; Owensby, L
We reviewed the available literature on the role of minimally invasive techniques for esophageal atresia (EA)/tracheoesophageal fistula (TEF) repair. No prospective studies have been published to date. According to the recent classification of the Oxford Centre for Evidence based Medicine, the best available evidence for studies comparing the minimally invasive versus open approach for EA/TEF repair is Level 3 (a, b). Similar postoperative results of the thoracoscopic versus conventional repair are confirmed in four retrospective comparative studies and one meta-analysis. However, the available data on complications and postoperative esophageal function are derived from series operated by experienced surgeons in specialized centers. More data on the impact of the learning curve are mandatory before a recommendation on a widespread use can be made. Patient selection and a low threshold for conversion may further improve results. PMID:23720207
Dingemann, Carmen; Ure, Benno M
Esophageal atresia with tracheoesophageal fistula (TEF with EA) is a common disease which is associated with many other congenital abnormalities. The most common association is with VACTERL syndrome.. Various types of ear malformations have been reported in CHARGE syndrome associated with EA and TEF. However, absence of external ear has not been described which is being reported in this article. We could not found this association even on extensive search of literature. PMID:23904729
Upadhyaya, Vijai D; Gangopadhyay, Ajay N; Srivastava, Punit K; Hasan, Zaheer; Sharma, Shiv P
Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative. PMID:23569349
Zhou, Yong; Wu, Xu-Dong; Shi, Quan; Jia, Jing
Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.
Zhou, Yong; Wu, Xu-Dong; Shi, Quan; Jia, Jing
The functional esophageal disorders include globus, rumination syndrome, and symptoms that typify esophageal diseases (chest pain, heartburn, and dysphagia). Factors responsible for symptom production are poorly understood. The criteria for diagnosis rest not only on compatible symptoms but also on exclusion of structural and metabolic disorders that might mimic the functional disorders. Additionally, a functional diagnosis is precluded by the presence of a pathology-based motor disorder or pathological reflux, defined by evidence of reflux esophagitis or abnormal acid exposure time during ambulatory esophageal pH monitoring. Management is largely empirical, although efficacy of psychopharmacological agents and psychological or behavioral approaches has been established for serveral of the functional esophageal disorders. As gastroesophageal reflux disease overlaps in presentation with most of these disorders and because symptoms are at least partially provoked by acid reflux events in many patients, antireflux therapy also plays an important role both in diagnosis and management. Further understanding of the fundamental mechanisms responsible for symptoms is a priority for future research efforts, as is the consideration of treatment outcome in a broader sense than reduction in esophageal symptoms alone. Likewise, the value of inclusive rather than restrictive diagnostic criteria that encompass other gastrointestinal and non-gastrointestinal symptoms should be examined to improve the accuracy of symptom-based criteria and reduce the dependence on objective testing.???Keywords: globus; rumination; chest pain; esophageal motility disorders; esophageal spasm; gastroesophageal reflux disease; Rome II
Clouse, R; Richter, J; Heading, R; Janssens, J; Wilson, J
... they can bleed severely. Any type of chronic liver disease can cause esophageal varices. Varices can also occur ... People with chronic liver disease and esophageal varices may have no symptoms. If there is only a small amount of bleeding, the only symptom ...
The aberrant DNA methylation of tumor suppressor genes is well documented in esophageal cancer, including adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) as well as in Barrett's esophagus (BE), a pre-malignant condition that is associated with chronic acid reflux. BE is a well-recognized risk factor for the development of EAC, and consequently the standard of care is for individuals with BE to be placed in endoscopic surveillance programs aimed at detecting early histologic changes that associate with an increased risk of developing EAC. Yet because the absolute risk of EAC in individuals with BE is minimal, a clinical need in the management of BE is the identification of additional risk markers that will indicate individuals who are at a significant absolute risk of EAC so that they may be subjected to more intensive surveillance. The best currently available risk marker is the degree of dysplasia in endoscopic biopsies from the esophagus; however, this marker is suboptimal for a variety of reasons. To date, there are no molecular biomarkers that have been translated to widespread clinical practice. The search for biomarkers, including hypermethylated genes, for either the diagnosis of BE, EAC, or ESCC or for risk stratification for the development of EAC in those with BE is currently an area of active research. In this review, we summarize the status of identified candidate epigenetic biomarkers for BE, EAC, and ESCC. Most of these aberrantly methylated genes have been described in the context of early detection or diagnostic markers; others might prove useful for estimating prognosis or predicting response to treatment. Finally, special attention will be paid to some of the challenges that must be overcome in order to develop clinically useful esophageal cancer biomarkers. PMID:22406828
Kaz, Andrew M; Grady, William M
Eosinophilic esophagitis and eosinophilic gastroenteritis is being recognized more frequently among the adult patients. The disease is characterized by massive infiltration of the wall of gastrointestinal tract by sheets of eosinophils. The clinical features depend upon the site of involvement. They include dyspepsia, dysphagia, nausea, vomiting, chest pain, diarrhea and protein-losing enteropathy. Eosinophilic esophagitis may present as chest pain, dysphagia or dyspepsia. The characteristic endoscopic feature of eosinophilic esophagitis is the formation of fine concentric mucosal rings (corrugated esophagus). Regarding the pathogenesis of these mucosal rings our hypothesis is that mast cells in the esophageal wall in response to allergens release histamine, eosinophilic chemotactic factor and platelet activating factor, etc. which activate eosinophils to release toxic cationic proteins. Activation of acetyl choline by histamine may cause contraction of the muscle fibers in the muscularis mucosae resulting in the formation of esophageal rings. This hypothesis can be tested by demonstrating the contraction of muscle layers of muscularis mucosae with the use of high frequency endoscopic ultrasonic probe introduced via the biopsy channel of an endoscope. PMID:15617859
Mann, N S; Leung, J W
We report the case of a 65-year-old woman who presented to the Hermanos Ameijeiras Hospital in Cuba due to dysphagia for the previous 5 months. Forty years previously, she had undergone esophagocoloplasty for caustic esophagitis. Adenocarcinoma was diagnosed in the colonic interposition. The tumor was resected with oncologic margins and food transit was successfully restored. PMID:16420883
Martín, Miguel Angel; Ferrás, Albio
Advances in molecular genetics have accelerated the understanding of the genetic basis of many diseases. This is particularly true for esophageal adenocarcinoma with its well-defined premalignant lesions. At the same time, remarkable progress in recombinant DNA technology has enabled the development of molecular treatments for inherited disorders, infectious diseases and cancer. In recent years, especially the development of gene therapy
Christianne J. Buskens; Willem A. Marsman; Piter J. Bosma; J. Jan B. van Lanschot
Background Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis. Methods The expression of CDX2 hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: <10 weeks; Group B: 10–30 weeks; Group C: >30 weeks). Results No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. De novo Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (p = 0.001). Conclusion De novo expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma.
Since 1962, the Waterston classification has been used to stratify neonates who have esophageal atresia (EA) and\\/or tracheoesophageal fistula (TEF) into prognostic categories based on birth weight, the presence of pneumonia, and the identification of other congenital anomalies. In response to advances in neonatal care, the surgeons from the Montreal Children's Hospital proposed a new categorization system in 1993 in
Steven Teich; Daniel P Barton; Margaret E Ginn-Pease; Denis R King
MicroRNAs (miRNAs) can act as oncogenes or tumor suppressors and modulate the expression of approximately one-third of all human genes. To test the hypothesis that adverse alleles in miRNA-related genes may increase the risk for esophageal cancer, we assessed the associations between esophageal cancer risk and 41 potentially functional single-nucleotide polymorphisms (SNPs) in 26 miRNA-related genes in a case-control study of 346 Caucasian esophageal-cancer patients (85.5% with esophageal adenocarcinoma) and 346 frequencymatched (age, gender, and ethnicity) controls. Seven SNPs were significantly associated with esophageal cancer risk. The most notable finding was that the SNP rs6505162, which is located in the pre-mir423 region, was associated with a per-allele odds ratio of 0.64 (95% confidence interval [CI], 0.51-0.80; P for trend < 0.0001). This association remained significant after we corrected for multiple comparisons. A common haplotype of the GEMIN4 gene was associated with a significantly reduced risk of esophageal cancer (odds ratio = 0.65; 95% CI, 0.42-0.99). We performed a combined unfavorable genotype analysis to further evaluate the cumulative effects of the promising (risk-associated) SNPs. In comparison with the low-risk group (fewer than three unfavorable genotypes), the medium-risk group (three unfavorable genotypes) had a 2.00-fold (95% CI=1.31-3.08) increased risk and the high-risk group (more than three unfavorable genotypes) had a 3.14-fold (95% CI=2.03-4.85) increased risk (P for trend < 0.0001). Results for the risk of esophageal adenocarcinoma were similar to the overall risk results. The present study provides the first evidence that miRNAs may affect esophageal cancer risk in general and that specific genetic variants in miRNA-related genes may affect esophageal cancer risk individually and jointly.
Ye, Yuanqing; Wang, Kenneth K.; Gu, Jian; Yang, Hushan; Lin, Jie; Ajani, Jaffer A.
Esophageal neoplasms have a wide spectrum of clinical features, pathologic findings, and imaging manifestations. Leiomyomas are the most common benign esophageal neoplasm, typically appearing as smoothly marginated intramural masses. Fibrovascular polyps arise in the cervical esophagus, gradually elongating as they are pulled inferiorly by esophageal peristalsis. Granular cell tumors are generally incidental small intramural masses with an appearance similar to that of leiomyomas. Malignant esophageal neoplasms are a common cause of cancer mortality, particularly squamous cell carcinoma (SCC) and adenocarcinoma. Both of these tumors occur in older men, most often appearing as irregular infiltrative lesions at barium examination, with evidence of tumor spread beyond the esophagus at cross-sectional imaging. Adenocarcinoma arises from Barrett esophagus and is much more likely than SCC to involve the gastroesophageal junction. Esophageal involvement by lymphoma is usually secondary to tumor spread from the stomach or mediastinum. Spindle cell carcinoma is a biphasic malignancy with carcinomatous and sarcomatous elements that forms a bulky polypoid intraluminal mass. Neuroendocrine carcinoma is an aggressive neoplasm that may be hypervascular and is usually associated with metastatic disease at presentation. Understanding the imaging appearances and pathologic bases of esophageal neoplasms is essential for their detection, differential diagnosis, staging, and treatment planning. PMID:23842973
Lewis, Rachel B; Mehrotra, Anupamjit K; Rodriguez, Pablo; Levine, Marc S
Hedgehog (Hh) signaling is frequently activated in human cancer, including esophageal cancer. Most esophageal cancers are diagnosed in the advanced stages, therefore, identifying the very alterations that drive esophageal carcinogenesis may help designing novel strategies to diagnose and treat the disease. Analysis of Hh signaling in precancerous lesions is a critical first step in determining the significance of this pathway for carcinogenesis. Here we report our data on Hh target gene expression in 174 human esophageal specimens [28 esophageal adenocarcinomas (EAC), 19 Barrett’s esophagus, 103 cases of esophageal squamous cell carcinoma (ESCC), and 24 of squamous dysplastic lesions], and in two rat models of esophageal cancer. We found that 96% of human EAC express Hh target genes. We showed that PTCH1 expression is the most reliable biomarker. In contrast to EAC, only 38% of ESCC express Hh target genes. We found activation of Hh signaling in precancerous lesions of ESCCs and EACs in different degrees (21% and 58% respectively). Expression of Hh target genes is frequently detected in severe squamous dysplasia/ carcinoma in situ (p=0.04) and Barrett’s esophagus (p=0.01). Unlike EAC, sonic hedgehog (Shh) expression was rare in ESCCs. Consistent with the human specimen data, we found a high percentage of Hh signaling activation in precancerous lesions in rat models. These data indicate that Hh signaling activation is an early molecular event in the development of esophageal cancer, particularly EAC.
Yang, Ling; Wang, Li-Shu; Chen, Xiaoxin (Luke); Gatalica, Zoran; Qiu, Suimin; Liu, Zhihua; Stoner, Gary; Zhang, Hongwei; Weiss, Heidi; Xie, Jingwu
There are very few xenograft models available for the study of esophageal (E) and gastro-esophageal junction (GEJ) cancer. Using a NOD/SCID model, we implanted 90 primary E and GEJ tumors resected from patients and six endoscopic biopsy specimens. Of 69 resected tumors with histologically confirmed viable adenocarcinoma or squamous cell carcinoma, 22 (32%) was engrafted. One of 11 tumors, considered to have had a complete pathological response to neo-adjuvant chemo-radiation, also engrafted. Of the 23 patients whose tumors were engrafted, 65% were male; 30% were early stage while 70% were late stage; 22% received neo-adjuvant chemo-radiation; 61% were GEJ cancers. Engraftment occurred in 18/54 (33%) adenocarcinomas and 5/16 (31%) squamous cell carcinomas. Small endoscopic biopsy tissue had a 50% (3/6) engraftment rate. Of the factors analyzed, pretreatment with chemo-radiation and well/moderate differentiation showed significantly lower correlation with engraftment (P<0.05). In the subset of patients who did not receive neo-adjuvant chemo-radiation, 18/41 (44%) engrafted compared with those with pretreatment where 5/29 (17%, P=0.02) engrafted. Primary xenograft lines may be continued through 4-12 passages. Xenografts maintained similar histology and morphological characteristics with only minor variations even after multiple passaging in most instances. PMID:23399854
Dodbiba, Lorin; Teichman, Jennifer; Fleet, Andrew; Thai, Henry; Sun, Bin; Panchal, Devang; Patel, Devalben; Tse, Alvina; Chen, Zhuo; Faluyi, Olusola O; Renouf, Daniel J; Girgis, Hala; Bandarchi, Bizhan; Schwock, Joerg; Xu, Wei; Bristow, Robert G; Tsao, Ming-Sound; Darling, Gail E; Ailles, Laurie E; El-Zimaity, Hala; Liu, Geoffrey
Metastatic involvement (59.2%) was noted in esophageal cancer during autopsy on 710 cases, with lymphogenic metastasis predominating over hematogenic metastasis. In those dying soon after radiation therapy there were metastasis in 49% and in 30% after sur...
A. I. Pirogov V. D. Ryndin
... the type of cells that become malignant (cancerous): Squamous cell carcinoma : Cancer that begins in squamous cells , the thin, ... chance of developing esophageal cancer increases with age. Squamous cell carcinoma of the esophagus is more common in blacks ...
Eosinophilic esophagitis (EE) is an emerging worldwide food allergic disorder associated with polysensitization to multiple food allergens, resulting in greatly restricted diets and chronic gastroesophageal reflux disease-like symptoms in many individuals...
M. E. Rothenberg
Eosinophilic esophagitis (EE) is an emerging worldwide food allergic disorder associated with polysensitization to multiple food allergens, resulting in greatly restricted diets and chronic gastroesophageal reflux disease-like symptoms in many individuals...
Esophageal carcinoma is the fifth most common gastrointestinal cancer, and the recent data suggests that it is rising in incidence\\u000a faster than any other malignancy. Although esophageal carcinoma is generally felt to have a poor prognosis, this is largely\\u000a owing to the heterogeneity of patients. As with any malignancy, the stage of the tumor predicts prognosis and determines treatment\\u000a options.
Jason Vollweiler; Gregory Zuccaro
Small numbers of intraepithelial esophageal eosinophils (IEE) may be seen in 50% of patients with gastroesophageal reflux disease and occasionally in normal volunteers. High concentrations of IEE are rarely seen in either setting. During a two-year period we idetified 12 adult patients with very dense eosinophil infiltrates in esophageal biopsies (defined as >20 IEE\\/high-power field). Dysphagia was the presenting complaint
Stephen E. A. Attwood; Thomas C. Smyrk; Tom R. Demeester; James B. Jones
The esophagus is a hollow muscular tube with ends closed proximally and distally by muscular sphincters. The upper esophageal sphincter and proximal one third of the esophageal body are composed of striated muscle. There is then a transition zone where striated and smooth muscle mix together. The lower esophageal sphincter and the distal one half to two thirds of the
Diffuse esophageal spasm is an uncommon motility disorder that is found in less than 5% of patients undergoing esophageal motility testing for dysphagia. It is defined manometrically by the presence of 20% or more simultaneous contractions in the distal esophageal body with normal peristalsis. This motility abnormality has been traditionally identified as occurring primarily in the smooth muscle portion of
Monicca Sperandio; Radu Tutuian; R. Matthew Gideon; Philip O. Katz; Donald O. Castell
The authors report the case of lower carvical\\/ upper thoracic esophageal duplication associated with an obstructing esophageal web. This presented in the newborn period as an esophageal atresia. Initial resection of the web and closure of the fistula were performed. The duplication was excised electively at 2 months of age. Persistent symptomatic tracheomalacia required aortopexy, after which the child recovered
Charles L Snyder; Steven W Bickler; George K Gittes; V Ramachandran; Keith W Ashcraft
This article reviews the current management of esophageal cancer, including staging and treatment options, as well as providing support for using multidisciplinary teams to better manage esophageal cancer patients. PMID:23453332
Mulligan, Charles R
... tests to evaluate for achalasia and other esophageal motility disorders is manometry. This test is performed on an outpatient basis. A small ... coordination of contractions of the esophageal muscles. Some motility disorders, including ... TREATMENTS ARE AVAILABLE FOR ACHALASIA? Endoscopic Treatment ...
MENU Return to Web version Esophageal Atresia and Tracheoesophageal Fistula Overview What is esophageal atresia? In babies who ... swallows gets into the stomach. What is a tracheoesophageal fistula? A fistula (say “fist-you-lah”) is a ...
Cancers of the esophagus, stomach and colon contribute to a major health burden worldwide and over 20% of all cancer deaths. Biomarkers that should indicate pathogenic process and are measureable in an objective manner for these tumors are rare and not established in the clinical setting. In general biomarkers can be very useful for cancer management as they can improve clinical decision-making regarding diagnosis, surveillance, and therapy. Biomarkers can be different types of molecular entities (such as DNA, RNA or proteins), which can be detected, in different tissues or body fluids. However, more important is the type of biomarker itself, which allows diagnostic, prognostic or predictive analyses for different clinical problems. This review aims to systematically summarize the recent findings of genetic and epigenetic markers for gastrointestinal tumors within the last decade. While many biomarkers seem to be very promising, especially if used as panels, further development is urgently needed to address practical considerations of biomarkers in cancer treatment. PMID:23791941
Tänzer, Marc; Liebl, Magdalena; Quante, Michael
Esophageal perforation is usually an acute, life-threatening event, and its diagnosis can be established on the basis of obvious clinical and radiographic findings. This article describes two cases whereby symptoms of esophageal perforations were masked by concomitant administration of steroids, thus causing marked delay in diagnosis and treatment. Esophageal rupture should be considered when patients receiving steroids develop unexplained fever
Linas M. Klygis; Rome Jutabha; Michael B. McCrohan; Arvydas D. Vanagunas
Reflux-induced injury promotes esophageal adenocarcinoma, one of the most rapidly increasing, highly lethal cancers in Western countries. Here we investigate the efficacy of a combinatorial chemoprevention strategy for esophageal adenocarcinoma and characterize the underlying molecular mechanisms. Specifically, our approach involves the use of Ursodeoxycholic acid (Urso) due to its ability to decrease injury-inducing bile salts in combination with Aspirin to mitigate the consequences of injury. We find that Urso-Aspirin combination reduces the risk of adenocarcinoma in-vivo in animals with reflux, decreases the proliferation of esophageal adenocarcinoma cells and down-regulates a key cell cycle regulator, CDK2. Mechanistically, using cell growth, luciferase-reporter, expression and ChIP assays, we identify GLI1, a Hedgehog-regulated transcription factor, as a novel target of Urso-Aspirin combination. We demonstrate that GLI1 is upregulated during esophageal carcinogenesis and GLI1 can bind to the CDK2 promoter and activate its expression. While the Urso-Aspirin combination downregulates GLI1, the GLI1 overexpression not only abrogates the effect of this combination on proliferation but it also restores CDK-2 expression. These findings support that the chemopreventive effect of the Urso-Aspirin combination occurs, at least in part, via a novel GLI1-CDK2-dependent mechanism. To further understand the regulation of CDK2 by GLI1, both pharmacologic and RNAi-mediated approaches demonstrate that GLI1 is a transcriptional activator of CDK2 and this regulation occurs independent of Smoothened, the central transducer of the Hedgehog canonical pathway. Collectively, these results identify a novel GLI1-to-CDK2 pathway in esophageal carcinogenesis, which is a bona fide target for effective combinatorial chemoprevention with Urso and Aspirin.
Rizvi, Sumera; DeMars, Cathrine J.; Comba, Andrea; Gainullin, Vladimir; Rizvi, Zaheer; Almada, Luciana L.; Wang, Kenneth; Lomberk, Gwen; Fernandez-Zapico, Martin E.; Buttar, Navtej S.
Cervical esophageal cancer and hypopharyngeal cancer represent a major diagnostic issue in early stages, considering the fact that the implication of both cervical esophageal and hypopharyngeal cancers shows a poor prognostic from the very beginning. Positive diagnosis can only be made after histopathological analysis and immunohistochemical analysis in addition. The bioptic material is sampled by rigid endoscopy this being the only viable method of assessing data on the tumor prior to the surgery. As much as 95% of tumors located at this site are epidermoid carcinomas with different staging and characteristics, other types of tumors being adenocarcinomas, lymphomas, etc. Several risk factors influence the biology of this site thus inflicting both cellular and molecular modifications that are the origin of cancer development. PMID:22732792
Popescu, B; Popescu, C R; Grigore, Raluca; Mogoant?, Carmen Aurelia; Ioni??, Elena; Moculescu, C; Berte?teanu, ? V G
Objective: To evaluate the outcome of aggressive conservative therapy in patients with esophageal perforation. Summary Background Data: The treatment of esophageal perforation remains controversial with a bias toward early primary repair, resection, and/or proximal diversion. This review evaluates an alternate approach with a bias toward aggressive drainage of fluid collections and frequent CT and gastographin UGI examinations to evaluate progress. Methods: From 1992 to 2004, 47 patients with esophageal perforation (10 proximal, 37 thoracic) were treated (18 patients early [<24 hours], 29 late). There were 31 male and 16 females (ages 18–90 years). The etiology was iatrogenic (25), spontaneous (14), trauma (3), dissecting thoracic aneurysm (3), and 1 each following a Stretta procedure and Blakemore tube placement. Results: Six of 10 cervical perforations underwent surgery (3 primary repair, 3 abscess drainage). Nine of 10 perforations healed at discharge. In 37 thoracic perforations, 2 underwent primary repair (1 iatrogenic, 1 spontaneous) and 4 underwent limited thoracotomy. Thirty-4 patients (4 cervical, 28 thoracic) underwent nonoperative treatment. Thirteen of the 14 patients with spontaneous perforation (thoracic) underwent initial nonoperative care. Overall mortality was 4.2% (2 of 47 patients). These deaths represent 2 of 37 thoracic perforations (5.4%). There were no deaths in the 34 patients treated nonoperatively. Esophageal healing occurred in 43 of 45 surviving patients (96%). Subsequent operations included colon interposition in 2, esophagectomy for malignancy in 3, and esophagectomy for benign stricture in 2. Conclusions: Aggressive treatment of sepsis and control of esophageal leaks leak lowers mortality and morbidity, allow esophageal healing, and avoid major surgery in most patients.
Vogel, Stephen B.; Rout, W Robert; Martin, Tomas D.; Abbitt, Patricia L.
Ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) commonly occurs secondary to neuroendocrine tumours and small cell carcinoma of lung. EAS has also been reported in association with gastric carcinoids. But, the occurrence of EAS secondary to gastric adenocarcinoma has rarely been reported. A 45-year-old male patient from Bangladesh presented with abdominal pain, jaundice and hyperpigmentation. Extensive work-up revealed poorly differentiating mucin-secreting adenocarcinoma of stomach with lymphangitis carcinomatosa of lung, bilateral adrenal metastasis and malignant common bile duct (CBD) stricture. Laboratory reports were suggestive for ectopic ACTH production. Most of these features are very rare in adenocarcinoma of stomach, and all these rare events occurring in a single patient is probably the rarest. PMID:22560823
Guha, Pradipta; Sahai, Shivesh Shankar; Sarkar, Debasis; Sardar, Partha; Mandal, Biplab; Das, Bidyut Kumar; Chatterjee, Sanjoy Kumar
The author reviewed 910 cases of consecutive esophageal biopsies in the last 15 year in the pathology laboratory of our hospital. There were 693 normal mucosa and benign lesions (76.2%) and 217 malignant lesions (23.8%). No significant changes were recognized in the esophagus in 50 biopsies (5.5%). In benign lesions, the number and frequency (percentages) were as follows: 263 chronic esophagitis (28.9%), 98 heterotopic gastric mucosa (10.8%), 3 heterotopic colonic mucosa (0.3%), 71 glycogenic acanthosis (7.8%), 68 candidiasis (7.5%), 35 benign ulcer (3.8%), 41 squamous papilloma (4.5%), 4 granular cell tumor (0.4%), 1 tubular adenoma (0.1%), 2 cytomegalovirus esophagitis (0.2%), 3 leiomyoma (0.3%), 17 basal cell hyperplasia (1.9%), and 37 Barrett’s epithelium (4%). In malignant lesions, the number and frequency (percentages) were as follows: 53 mild dysplasia (5.8%), 29 moderate dysplasia (3.2%), 31 severe dysplasia (3.4%), 13 carcinoma in situ (1.4%), 68 squamous cell carcinoma (7.5%), 7 primary adenocarcinoma (0.8%), 1 primary signet ring cell carcinoma (0.1%), 4 primary small cell carcinoma (0.4%), 2 primary amelanotic malignant melanoma (0.2%), 1 primary undifferentiated sarcoma (0.1%), 7 gastric cancer invasion (0.8%), and 1 primary adenoid cystic carcinoma (0.1%). In this article, the clinicopathologic features of these esophageal lesions were described.
This paper presents commentaries on whether eosinophilic esophagitis is a food allergy; inflammation in the context of eosinophilic esophagitis; whether eosinophilic esophagitis a cause of noncardiac chest pain; the role of endoscopy in the evaluation of eosinophilic esophagitis; and whether response to proton pump inhibitor therapy can distinguish eosinophilic esophagitis from gastroesophageal reflux disease. PMID:24117638
Chehade, Mirna; Lucendo, Alfredo J; Achem, Sami R; Souza, Rhonda F
Esophageal motility testing is the method of choice in evaluating esophageal motor disorders. Some physicians, however, question the clinical utility of esophageal motility testing, since the results are often normal in symptomatic patients. The clinical utility of esophageal motility testing is reviewed for patients with a complaint of noncardiac chest pain, dysphagia or symptoms of gastroesophageal reflux disease. Esophageal motility
Melvin L. Allen; Richard B. Lynn; Saeed Zamani
Spontaneous esophageal rupture is an uncommon and poorly understood condition. Recurrent rupture is extremely rare, with only one previously reported case in the literature. Here, we present a case series of two patients who had recurrent ruptures, and discuss the principles underlying the management of such cases.
Omar A. Khan; Clifford W. Barlow; David F. Weeden; Khalid M. Amer
Herpes simplex virus esophagitis has rarely been reported in immunocompetent children. We describe 2 immunocompetent wrestlers on the same team who presented with fever, odynophagia, and dysphagia. Histologic examination of the esophagus showed ulceration and exudate, herpes simplex virus was detected by polymerase chain reaction. We propose that wrestling may be a mode of transmission for this disease. PMID:21544004
Khlevner, Julie; Beneri, Christy; Morganstern, Jeffrey A
... determine if you have a ring or a web, your doctor may order one of these tests: Barium swallow test. This allows the radiologist to ... contribute to the development of esophageal rings and webs, your doctor probably will order a blood test for iron levels and, if you are deficient, ...
Esophageal manometry was performed in 20 patients with esophagopharyngeal regurgitation, in 20 patients with severe chronic heartburn but without regurgitation, and in 20 normal subjects. The purpose of the procedure was to identify possible differences between these groups in upper esophageal sphincter and lower esophageal sphincter resting pressures, and in amplitude of peristaltic contraction in the distal esophagus. The mean peak upper esophageal sphincter pressures in normal subjects and in patients with chronic heartburn were significantly greater than in the patients with esophagopharyngeal regurgitation (101 and 108 vs. 54 mmHg, respectively). In the normal subjects, the mean lower esophageal sphincter resting pressure (19 mmHg) was significantly greater than for the heartburn group (14 mmHg) and for the patients with esophagopharyngeal regurgitation (10 mmHg). The amplitude of peristalsis was significantly lower in the group with regurgitation than in both normal subjects and the group with chronic heartburn. Nine normal subjects responded to intraesophageal infusion of 0.9% NaCl and 0.1 N HCl with a significant increase in upper esophageal sphincter resting pressure, but the group with esophagopharyngeal regurgitation showed no significant change. Patients with esophagopharyngeal regurgitation have lower esophageal sphincter hypotension, diminished peristaltic amplitude, upper esophageal sphincter hypotension, and diminished upper esophageal sphincter response to intraesophageal fluid. We conclude there is in these patients a breakdown of several normal esophageal mechanisms which ordinarily serve as barriers to esophagopharyngeal regurgitation. PMID:7053042
Gerhardt, D C; Castell, D O; Winship, D H; Shuck, T J
...Devices Â§ 878.3610 Esophageal prosthesis. (a) Identification. An esophageal prosthesis is a rigid, flexible, or expandable tubular device made of a...esophagus. The metal esophageal prosthesis may be uncovered or...
...Devices Â§ 878.3610 Esophageal prosthesis. (a) Identification. An esophageal prosthesis is a rigid, flexible, or expandable tubular device made of a...esophagus. The metal esophageal prosthesis may be uncovered or...
Despite early surgical repair, congenital esophageal atresia with or without tracheoesophageal fistula (EA ± TEF) has long-term effects on respiratory and gastrointestinal function. This review updates summarizes research published since 2003 on long-term respiratory complications in patients with a history of EA ± TEF. Pulmonary hypoplasia appears to not be rare in patients with EA ± TEF. Tracheomalacia is common and is associated with respiratory symptoms in childhood. Aspiration, associated with esophageal dysmotility and/or gastroesophageal reflux, may lead to reduced pulmonary function and bronchiectasis. Pulmonary function is generally normal, although lower than in control patients, and restrictive defects tend to be commoner than obstructive defects. Abnormal airway reactivity is common and, along with respiratory symptoms, is associated with atopy. However, the inflammatory profile in EA ± TEF patients based on bronchial biopsies and exhaled nitric oxide differs from typical allergic asthma. Recent studies suggest that in older patients, respiratory symptoms tend to be associated with atopy, but abnormal lung function tends to be associated with gastroesophageal reflux and with chest wall abnormalities. Early detection and management of aspiration may be important to help prevent decrements in pulmonary function and serious long-term complications in EA ± TEF patients. PMID:23679034
BACKGROUND: The progression from Barrett's metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA) has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to
Eileen Looby; Mohamed MM Abdel-Latif; Veronica Athié-Morales; Shane Duggan; Aideen Long; Dermot Kelleher
Cytochrome P450 epoxygenases (CYP450) have been recently shown to promote malignant progression. Here we investigated the mRNA and protein expression and potential clinical relevance of CYP2C9 in esophageal cancer. Highest expression was detected in esophageal adenocarcinoma (EAC; n=78) and adjacent esophageal mucosa (NEM; n=79). Levels of CYP2C9 in EAC and NEM were significantly higher compared to esophageal squamous cell carcinoma (ESCC; n=105). Early tumor stages and well-differentiated tumors showed a significantly higher CYP2C9 expression compared to progressed tumors. Moreover, CYP2C9 expression was correlated to high Ki-67 labeling indices in EAC and Ki-67 positive tumor cells in EAC and ESCC. Selective inhibition of CYP2C9 decreased tumor cell proliferation (KYSE30, PT1590 and OE19) in vitro, which was abolished by 11,12-epoxyeicosatrienoic acid (11,12-EET). Cell-cycle analysis using FACS revealed that inhibition of CYP2C9 leads to a G0/G1 phase cell-cycle arrest. CYP2C9 seems to be relevant for early esophageal cancer development by promoting tumor cell proliferation. Pharmacological inhibition of CYP2C9 might contribute to a more efficient therapy in CYP2C9 highly expressing esophageal cancers. PMID:21167292
Schmelzle, Moritz; Dizdar, Levent; Matthaei, Hanno; Baldus, Stephan E; Wolters, Judith; Lindenlauf, Nina; Bruns, Ingmar; Cadeddu, Ron-Patrick; Kröpil, Feride; Topp, Stefan A; Schulte am Esch, Jan; Eisenberger, Claus F; Knoefel, Wolfram T; Stoecklein, Nikolas H
Nonmuscle myosin IIA (myosin IIA) is a force-producing protein involved in the process of cell migration. Its expression has been considered as a bad prognostic indicator in stage I lung adenocarcinoma. However, the expression and clinical significance of myosin IIA in esophageal cancer has not been explored. In this study, we investigate the expression level of myosin IIA in 50 esophageal squamous cancer and 30 adjacent normal esophageal tissues by immunohistochemical staining and correlated its expression with clinicopathological features. Myosin IIA was expressed in all esophageal squamous cancer tissues (100%) and 8 of 30 adjacent normal tissues (26.7%, P = 0.000). In cancer tissues, elevated myosin IIA expression level was significantly correlated with increasing metastatic lymph nodes, poorer cancer differentiation, and advanced tumor stage. Further univariate analysis suggested that strong myosin IIA expression was associated with a significantly shorter overall survival (P = 0.021). In addition, MYH9 SiRNA was transfected into esophageal squamous cancer cell line (KYSE-510) to study the role of myosin IIA in cell migration. SiRNA-mediated depletion of myosin IIA in KYSE-510 cells significantly increased cell-matrix adhesion and attenuated cell migration ability (P = 0.000). In conclusion, these findings indicate that overexpression of myosin IIA may contribute to the progression and poor prognosis of esophageal squamous cancer, and this effect may be associated with increased cancer cell migration. PMID:21951916
Xia, Z-K; Yuan, Y-C; Yin, N; Yin, B-L; Tan, Z-P; Hu, Y-R
\\u000a A subset of patients with esophageal\\u000a atresia (EA) have an associated short esophagus and require an\\u000a antireflux procedure. The Collis-Nissen procedure, which consists of a\\u000a combination of Collis gastroplasty and Nissen fundoplication, is\\u000a considered an option in such conditions. The long-term results of EA\\u000a patients undergoing this procedure have rarely been reported. The\\u000a results of the Collis-Nissen procedure were
Hisayoshi Kawahara; Kenji Imura; Makoto Yagi; Akio Kubota; Akira Okada
Bleeding per rectum is a common complaint in pediatric age group and mostly relates to benign conditions. Underlying colorectal carcinoma is a rare cause and carries a poor prognosis. We report two cases of mucinous adenocarcinoma of colon, one in a 9 years old male and other in a female of 12 years. The boy presented with rectal bleeding and increasing constipation of more than three years duration. He had mucinous adenocarcinoma (T3N0MX) of rectosigmoid region and underwent local complete resection of the tumor with colostomy. He also received postoperative chemotherapy and later underwent colostomy reversal. He is tumor free at two years follow up. The girl presented with signs of intestinal obstruction and at colonoscopy a stricture found in descending colon. The tumor was resected and biopsy reported as poorly differentiated mucinous adenocarcinoma with positive mesenteric nodes positive for tumor (T3N2MX). She is on chemotherapy.
Ahmed, Soofia; Akhtar, Jamshed
The objective of this paper is to study the dosimetric impact of respiratory gated radiotherapy in locally advanced esophageal carcinomaand to define the optimal respiratory phase for this treatment.The study included 8 consecutive patients with squamous-cell carcinoma (SCC) or histologically proved adenocarcinoma, for both at least T3–T4 NX or TX N1 M0 stage. Informed consent was obtained before beginning the
J. L. Dumas; A. Noël; D. Wolf; J. F. Bosset; P. Aletti
A wide variety of architectural patterns of adenocarcinoma may be seen in the prostate. We have recently encountered a hithertoundescribed pattern of growth characterized by intraluminal ball-like clusters of cancer cells reminiscent of renal glomeruli, which we refer to as prostatic adenocarcinoma with glomeruloid features. To define the architectural features, frequency, and distribution of prostatic adenocarcinoma with glomeruloid features, we
Anna Pacelli; Antonio Lopez-Beltran; A. J. Matthew Egan; David G Bostwick
OBJECTIVE:Increased expression of the inducible cyclooxygenase 2 (COX-2) enzyme has been detected in esophageal and colonic adenocarcinoma, and intake of aspirin and nonsteroidal anti-inflammatory drugs, known COX-2 inhibitors, have been associated with reduced tumor formation. Elevated COX-2 mRNA but variable protein expression has been demonstrated in Barrett's epithelium, and we have, therefore, sought to evaluate the expression of COX-2 protein
Clive D. Morris; Gordon R. Armstrong; Graham Bigley; Helen Green; Stephen E. A. Attwood
BACKGROUND: CREST (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasias) syndrome has been rarely associated with other malignancies (lung, esophagus).This is the first report of a primary adenocarcinoma of the third portion of the duodenum in a patient with CREST syndrome. CASE PRESENTATION: A 54-year-old male patient with CREST syndrome presented with colicky postprandial pain of the upper abdomen, diminished
Georgios Anastasopoulos; Athanasios Marinis; Christos Konstantinidis; Theodosios Theodosopoulos; Georgios Fragulidis; Ioannis Vassiliou
Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21, and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126, and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-?2 expression and increased tumor cell proliferation. Furthermore, we found that miR-126 expression was associated with tumor cell de-differentiation and lymph node metastasis, miR-16-2 was associated with lymph node metastasis, and miR-195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan-Meier analysis showed that miR-16-2 expression and miR-30e expression were associated with shorter overall and disease-free survival in all esophageal cancer patients. In addition, miR-16-2, miR-30e, and miR-200a expression were associated with shorter overall and disease-free survival in esophageal adenocarcinoma patients; however, miR-16-2, miR-30e, and miR-200a expression was not associated with overall or disease-free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR-30e and miR-16-2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR-34a in esophageal cancer also warrants further study.
Hu, Yuxin; Correa, Arlene M.; Hoque, Ashraful; Guan, Baoxiang; Ye, Fei; Huang, Jie; Swisher, Stephen G.; Wu, Tsung Teh; Ajani, Jaffer A.; Xu, Xiao-chun
Esophageal pain manifests as symptoms of heartburn, chest pain, or both. It shares features with other types of visceral pain\\u000a in that it is poorly characterized and not well localized, owing to the divergence of visceral afferents. The esophagus is\\u000a innervated by vagal and visceral spinal afferents, both of which are activated by noxious stimuli and convey information to\\u000a specific
Robert Lee; Ravinder K. Mittal
In spite of the interest paid by pediatric surgeons to esophageal atresia (EA) with tracheoesophageal fistula (TEF), no animal experimental model has been available for investigation. This preliminary report describes a reproducible fetal model of these malformations. Time-mated pregnant rats were given 1.5, 1.75, or 2 mg\\/kg of Adriamycin intraperitoneally on days 6 to 9 of gestation, and the litters
Juan A. Diez-Pardo; Qi Baoquan; C. Navarro; Juan A. Tovar
Esophageal adenocarcinoma (EAC) is characterized by resistance to chemotherapy and poor outcome. Although cisplatin (CDDP) has been used as a first-line therapy in patients with EAC, resistance remains a major clinical problem. The AXL receptor tyrosine kinase, originally isolated as a transforming gene from leukemia, is overexpressed in several solid tumors. Herein, we assessed AXL protein expression in human EACs and examined its role in CDDP resistance in human EAC cells. AXL overexpression was detected in more than 50% of tumors examined. Elevating AXL in nonoverexpressing cells doubled the CDDP IC(50) and increased cell survival three-fold, while attenuating AXL in overexpressing cells reduced survival two-fold. The effects of AXL modulation on cell survival were associated with changes in cellular and molecular markers of apoptosis. Mechanistic investigations revealed that AXL blocked CDDP-induced activation of endogenous p73? (TP73), reducing its protein half-life, and inhibited CDDP-induced levels of p-c-ABL(Y412) and p-p73?(Y99). These changes were associated with a disruption of c-ABL/p73? protein interactions due to association with c-ABL in the cytoplasm, thereby blocking nuclear accumulation of c-ABL and phosphorylation of p73? in response to DNA damage. Together, our results establish that AXL promotes CDDP resistance in esophageal adenocarcinoma and argue that therapeutic targeting of AXL may sensitize these cancers to DNA-damaging drugs. PMID:23117882
Hong, Jun; Peng, Dunfa; Chen, Zheng; Sehdev, Vikas; Belkhiri, Abbes
Background Esophageal adenocarcinoma (EAC) often presents at a late, incurable stage, and mortality has increased substantially, due to an increase in incidence of EAC arising out of Barrett’s esophagus. When diagnosed early, however, the combination of surgery and adjuvant therapies is associated with high cure rates. Metabolomics provides a means for non- invasive screening of early tumor-associated perturbations in cellular metabolism. Methods Urine samples from patients with esophageal carcinoma (n = 44), Barrett’s esophagus (n = 31), and healthy controls (n = 75) were examined using 1H-NMR spectroscopy. Targeted profiling of spectra using Chenomx software permitted quantification of 66 distinct metabolites. Unsupervised (principal component analysis) and supervised (orthogonal partial least-squares discriminant analysis OPLS-DA) multivariate pattern recognition techniques were applied to discriminate between samples using SIMCA-P+ software. Model specificity was also confirmed through comparison with a pancreatic cancer cohort (n = 32). Results Clear distinctions between esophageal cancer, Barrett’s esophagus and healthy controls were noted when OPLS-DA was applied. Model validity was confirmed using two established methods of internal validation, cross-validation and response permutation. Sensitivity and specificity of the multivariate OPLS-DA models were summarized using a receiver operating characteristic curve analysis and revealed excellent predictive power (area under the curve = 0.9810 and 0.9627 for esophageal cancer and Barrett’s esophagus, respectively). The metabolite expression profiles of esophageal cancer and pancreatic cancer were also clearly distinguishable with an area under the receiver operating characteristics curve (AUROC) = 0.8954. Conclusions Urinary metabolomics identified discrete metabolic signatures that clearly distinguished both Barrett’s esophagus and esophageal cancer from controls. The metabolite expression profile of esophageal cancer was also discrete from its precursor lesion, Barrett’s esophagus. The cancer-specific nature of this profile was confirmed through comparison with pancreatic cancer. These preliminary results suggest that urinary metabolomics may have a future potential role in non-invasive screening in these conditions.
Esophageal cancer incidence is increasing and has few treatment options. In studying receptor tyrosine kinases associated with esophageal cancers, we have identified EPHB4 to be robustly overexpressed in cell lines and primary tumor tissues. In total, 94 squamous cell carcinoma, 82 adenocarcinoma, 25 dysplasia, 13 Barrett esophagus, and 25 adjacent or unrelated normal esophageal tissues were evaluated by immunohistochemistry. EPHB4 expression was significantly higher in all the different histologic categories than in adjacent normal tissues. In 13 esophageal cancer cell lines, 3 of the 9 SCC cell lines and 2 of the 4 adenocarcinomas expressed very high levels of EPHB4. An increased gene copy number ranging from 4 to 20 copies was identified in a subset of the overexpressing patient samples and cell lines. We have developed a novel 4-nitroquinoline 1-oxide (4-NQO)-induced mouse model of esophageal cancer that recapitulates the EPHB4 expression in humans. A specific small-molecule inhibitor of EPHB4 decreased cell viability in a time- and dose-dependent manner in 3 of the 4 cell lines tested. The small-molecule inhibitor and an EPHB4 siRNA also decreased cell migration (12%-40% closure in treated vs. 60%-80% in untreated), with decreased phosphorylation of various tyrosyl-containing proteins, EphB4, and its downstream target p125FAK. Finally, in a xenograft tumor model, an EPHB4 inhibitor abrogated tumor growth by approximately 60% compared with untreated control. EphB4 is robustly expressed and potentially serves as a novel biomarker for targeted therapy in esophageal cancers. PMID:23100466
Hasina, Rifat; Mollberg, Nathan; Kawada, Ichiro; Mutreja, Karun; Kanade, Geetanjali; Yala, Soheil; Surati, Mosmi; Liu, Ren; Li, Xiuqing; Zhou, Yue; Ferguson, Benjamin D; Nallasura, Vidya; Cohen, Kenneth S; Hyjek, Elizabeth; Mueller, Jeffery; Kanteti, Rajani; El Hashani, Essam; Kane, Dorothy; Shimada, Yutaka; Lingen, Mark W; Husain, Aliya N; Posner, Mitchell C; Waxman, Irving; Villaflor, Victoria M; Ferguson, Mark K; Varticovski, Lyuba; Vokes, Everett E; Gill, Parkash; Salgia, Ravi
The following on molecular aspects of esophageal development contains commentaries on esophageal striated myogenesis and transdifferentiation; conversion from columnar into stratified squamous epithelium in the mouse esophagus; the roles for BMP signaling in the developing esophagus and forestomach; and evidence of a direct conversion from columnar to stratified squamous cells in the developing esophagus. PMID:21950820
Rishniw, Mark; Rodriguez, Pavel; Que, Jianwen; Burke, Zoe D; Tosh, David; Chen, Hao; Chen, Xiaoxin
The following on molecular aspects of esophageal development contains commentaries on esophageal striated myogenesis and transdifferentiation; conversion from columnar into stratified squamous epithelium in the mouse esophagus; the roles for BMP signaling in the developing esophagus and forestomach; and evidence of a direct conversion from columnar to stratified squamous cells in the developing esophagus.
Rishniw, Mark; Rodriguez, Pavel; Que, Jianwen; Burke, Zoe D.; Tosh, David; Chen, Hao; Chen, Xiaoxin
We report four cases of esophageal injury associated with the ingestion of commonly prescribed tablets or capsules. History and clinical characteristics of these cases suggest that the medications failed to transit the esophagus and acted locally to produce esophagitis. A search of English- and foreign-language medical journals documented 221 similar cases due to 26 different types of medication. While most
James Walter Kikendall; Arnold C. Friedman; Morakinyo Anthony Oyewole; David Fleischer; Lawrence F. Johnson
...Esophageal stethoscope with electrical conductors. 868.1920 Section...Esophageal stethoscope with electrical conductors. (a) Identification...esophageal stethoscope with electrical conductors is a device that...
...Esophageal stethoscope with electrical conductors. 868.1920 Section 868...Esophageal stethoscope with electrical conductors. (a) Identification. An esophageal stethoscope with electrical conductors is a device that is...
Esophageal leiomyosarcoma accounts for only 0.5% of all esophageal tumors. This rare tumor has been reported in middle-aged or elderly patients. In contrast, pediatric esophageal leiomyosarcomas have never been reported. The case described herein is the first report of an esophageal leiomyosarcoma in a pediatric patient with its own characteristics. The patient had symptoms of mild cough without dysphagia. The
Wen-xian Wang; Desai Gaurav; Li Wen; Ming-fu Ye; Qing-rong Sun; Wei-jin Liu; Dong Zhang
Background Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose–response, and duration of cigarette smoking cessation. Methods We used primary data from 10 population-based case–control studies and two cohort studies from the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided. Results The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose–response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and ?10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar. Conclusions Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.
Kamangar, Farin; Whiteman, David C.; Freedman, Neal D.; Gammon, Marilie D.; Bernstein, Leslie; Brown, Linda M.; Risch, Harvey A.; Ye, Weimin; Sharp, Linda; Pandeya, Nirmala; Webb, Penelope M.; Wu, Anna H.; Ward, Mary H.; Giffen, Carol; Casson, Alan G.; Abnet, Christian C.; Murray, Liam J.; Corley, Douglas A.; Nyren, Olof; Vaughan, Thomas L.; Chow, Wong-Ho
Background/Aims The management of asymptomatic erosive esophagitis is controversial. We surveyed physicians' opinions on asymptomatic erosive esophagitis using e-mail. Methods All members of the Korean Society of Neurogastro-enterology and Motility were invited to answer the questionnaire on the treatment and follow-up of patients with asymptomatic erosive esophagitis by e-mail. Results A total of 73 members answered the questionnaire (response rate, 18%). As initial management, 41% of respondents chose pharmacologic treatment, whereas 59% chose nonpharmacologic treatment. In the case of pharmacologic treatment, proton pump inhibitors were the preferred medication. The most common treatment duration was 4 weeks (43%), followed by 8 weeks (38%), and 6 months (11%). Sixty-two percent of the respondents recommended follow-up endoscopy annually, whereas 29% chose no endoscopic follow-up. Thirty-four percent of the respondents answered that they would talk about reflux-related sleep disturbances. Only 25% of the respondents explained the possibility of Barrett's esophagus or esophageal adenocarcinoma to their patients. Conclusions There are substantial practice variations in the management of asymptomatic erosive esophagitis in Korea.
Lim, Seong Woo; Kim, Jie-Hyun; Kim, Jeong Hwan; Kim, Heung Up; Jeon, Seong Woo
Opinion statement Cervical adenocarcinomas are increasing in incidence each year, comprising up to 25% of all cervical cancers diagnosed in\\u000a the United States. This increase largely reflects the inherent difficulty in detecting glandular precursor lesions using current\\u000a screening practices. However, there also appears to be a recent shift in the epidemiology of the disease process with younger\\u000a women being diagnosed more
John O. Schorge; Lynne M. Knowles; Jayanthi S. Lea
A 67-year-old male smoker presented with hemoptysis and recurrent pneumonia. Chest computed tomography showed an emphysematous cyst and air-fluid level cavities in the left lower lobe. A left lower lobectomy was performed. The intraoperative finding was intralobar sequestration. Histopathology revealed adenocarcinoma within the sequestrated lobe. Only 8 cases of lung cancer and sequestration have been reported since 1963. PMID:22160418
Lawal, Lukman; Mikroulis, Dimitrios; Eleftheriadis, Savvas; Karros, Panagiotis; Bougioukas, Ioannis; Bougioukas, Georgios
Gastroesophageal reflux (GER) is almost constant in esophageal atresia and tracheoesophageal fistula (EA/TEF). These patients resist medical treatment and require antireflux surgery quite often. The present review examines why this happens, the long-term consequences of GER and the main indications and results of fundoplication in this particular group of patients. The esophagus of EA/TEF patients is malformed and has abnormal extrinsic and intrinsic innervation and, consequently, deficient sphincter function and dysmotility. These anomalies are permanent. Fifty percent of patients overall have GER, and one-fifth have Barrett's metaplasia. Close to 100%, GER of pure and long-gap cases require fundoplication. In the long run, these patients have 50-fold higher risk of carcinoma than the control population. GER in EA/TEF does not respond well to dietary, antacid, or prokinetic medication. Surgery is necessary in protracted anastomotic stenoses, in pure and long-gap cases, and when there is an associated duodenal atresia. It should be indicated as well in other symptomatic cases when conservative treatment fails. However, confection of a suitable wrap is anatomically difficult in this condition as shown by a failure rate of 30% that is also explained by the persistence for life of the conditions facilitating GER. PMID:23679031
Tovar, J A; Fragoso, A C
Survival rates in esophageal atresia (EA) patients have reached 90%. In long-term follow-up studies the focus has shifted from purely surgical or gastrointestinal evaluation to a multidisciplinary approach. We evaluated the long-term morbidity in adolescent and adult EA patients and discussed mainly nonsurgical issues. Dysphagia is common and reported in up to 85% of patients. In young adults gastroesophageal reflux disease occurs frequently with development of Barrett esophagus in 6% reported in different series. It is difficult to estimate respiratory morbidity from the literature because many different definitions, questionnaires, and study designs have been used. However, many patients seem to suffer from respiratory problems even into adulthood. In conclusion, morbidity is not only restricted to surgical problems but many different domains are involved. These are all related and together determine to a large extent the quality of life of EA patients and also of their families. We assume that a multidisciplinary care approach seems best to address their special needs. PMID:23679035
Ijsselstijn, H; van Beelen, N W G; Wijnen, R M H
When radiation therapy is used for palliation of obstruction in patients with advanced esophageal carcinoma, an improvement in dysphagia can be expected in approximately 50% of patients. Major objective responses have rarely been quantitied but, in one study, were seen in 33% patients. Recurrence of dysphagia is usually seen within 2-6 months of treatment. Radiation toxicities and complications, even when used with palliative intent, can be substantial and include esophagitis, tracheoesophageal or esophageal-aortic fistula, mediastinitis, hemorrhage, pneumonitis, and myelosuppression. (JMT)
The principal radionuclide procedures involved in the evaluation of esophageal disorders that are amenable to surgery are illustrated and briefly described. The role of the radionuclide esophagogram (RE) in the diagnosis and management of achalasia, oculopharyngeal muscular dystrophy and its complications, tracheoesophageal fistulae, pharyngeal and esophageal diverticulae, gastric transposition, and fundoplication is discussed. Detection of columnar-lined esophagus by Tc-99m pertechnetate imaging and of esophageal carcinoma by Ga-67 citrate and Tc-99m glucoheptonate studies also is presented. 37 references.
Taillefer, R.; Beauchamp, G.; Duranceau, A.C.; Lafontaine, E.
The A-kinase anchoring protein 12 (AKAP12) is a kinase scaffold protein with known tumor suppressor activity. Recently, AKAP12 promoter hypermethylation was reported in gastric and colorectal cancers. We examined AKAP12 promoter hypermethylation using real-time methylation-specific PCR in 259 human esophageal tissues. AKAP12 hypermethylation showed highly discriminative receiver-operator characteristic (ROC) curve profiles, clearly distinguishing esophageal adenocarcinoma (EAC) from esophageal squamous cell carcinoma and normal esophagus (P < 0.0001). AKAP12-normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's, and EAC than in normal esophagus (P < 0.0000001). AKAP12 hypermethylation frequency was zero in normal esophagus but increased early during neoplastic progression, to 38.9% in BE from patients with Barrett's alone, 52.5% in dysplastic Barrett's metaplasia, and 52.2% in EAC. AKAP12 hypermethylation levels were significantly higher in normal esophageal epithelia from patients with EAC (mean = 0.00082) than in normal esophagi from patients without Barrett's or esophageal cancer (mean = 0.00007; P = 0.006). There was a significant correlation between AKAP12 hypermethylation and BE segment length, a known clinical neoplastic progression risk factor. In contrast, only 2 (7.7%) of 26 esophageal squamous cell carcinomas exhibited AKAP12 hypermethylation. Treatment of BIC and OE33 EAC cells with 5-aza-2'-deoxycytidine reduced AKAP12 methylation and increased AKAP12 mRNA expression. AKAP12 mRNA levels in EACs with unmethylated AKAP12 (mean = 0.1663) were higher than in EACs with methylated AKAP12 (mean = 0.0668). We conclude that promoter hypermethylation of AKAP12 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker for the early detection of EAC. PMID:18199717
Jin, Zhe; Hamilton, James P; Yang, Jian; Mori, Yuriko; Olaru, Alexandru; Sato, Fumiaki; Ito, Tetsuo; Kan, Takatsugu; Cheng, Yulan; Paun, Bogdan; David, Stefan; Beer, David G; Agarwal, Rachana; Abraham, John M; Meltzer, Stephen J
Tracheal mucosal damage has been reported in autopsy specimens of cases with proximal esophageal atresia and distal tracheoesophageal fistula (EA-TEF) (Gross classification type C). Such changes have not been reported for isolated EA (Gross classification type A). Our hypothesis is that passage of amniotic fluid (AF) through fistula via larynx and trachea may damage tracheal mucosa. An experimental study was conducted to investigate this hypothesis in the Adriamycin-induced EA-TEF model. In the first stage of the study, we tested whether the fetuses with EA-TEF associated with pyloric atresia cannot swallow AF whereas the fetuses EA-TEF without intestinal atresia can swallow AF. Carbon solution was injected into the AF for this purpose. In the second stage of study, at the 21st day of their gestation, fetuses were extirpated and dissected under microscope. In both stages, fetuses were divided into four groups as control, fetuses without tracheoesophageal abnormalities, fetuses with EA-TEF only, fetuses with pyloric atresia associated with EA-TEF. Lungs and tracheas of the all fetuses were removed for histopathological examination. While carbon particles were present in the trachea, stomachs of the fetuses without tracheoesophageal anomalies, with EA-TEF only and control fetuses, carbon particles were absent in both trachea and stomachs of the fetuses with pyloric atresia associated with EA-TEF. Histopatological examination of the tracheal mucosa showed damage throughout the trachea in the fetuses with EA-TEF only group. Tracheal mucosa was found to be normal in other groups. Bronchial mucosa and lung tissues were found to be normal in all groups. Amniotic fluid swallowed through the TEF causes histopathological changes in the tracheal mucosa of the fetuses with EA-TEF only group. These findings may also contribute to the development of new fetal treatment modalities. PMID:16871620
Ate?, O?uz; Hakgüder, Gülce; Olguner, Mustafa; Ozer, Erdener; Akgür, Feza M
A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly sug- gest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement. Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus. Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease, important barriers remain that need to be addressed.
Totonelli, Giorgia; Maghsoudlou, Panagiotis; Fishman, Jonathan M; Orlando, Giuseppe; Ansari, Tahera; Sibbons, Paul; Birchall, Martin A; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo
The charts of 83 children with chest pain who underwent esophageal manometry followed by esophagogastroscopy were reviewed. Forty-seven (57%) had normal esophageal histology and normal motility (group I). Esophagitis and normal motility were demonstrated in 15 children (group II), normal esophageal histology and esophageal dysmotility in 13 (group III), and both esophagitis and abnormal motility in 8 (group IV). Diffuse
Mark S. Glassman; Marvin S. Medow; Stuart Berezin; Leonard J. Newman
The aim of the present study was to investigate esophageal motor function by means of krypton-81m esophageal transit scintigraphy and to compare the results with the functional and morphological data obtained by means of triple lumen manometry and endoscopy. In acute and subacute stages of the disease, all clinical, anatomical, and functional parameters were in good agreement, revealing significant impairment. In chronic stages, the severity of the dysphagia was not correlated to the importance of the residual stenosis. Conversely, 81mKr esophageal transit and manometric's findings were in good agreement with the clinical symptoms, during the entire follow-up period ranging between 3 months to 7 years. The 81mKr test is undoubtedly the easiest and probably the most physiological technique currently available for long-term functional evaluation of caustic esophagitis.
Cadranel, S.; Di Lorenzo, C.; Rodesch, P.; Piepsz, A.; Ham, H.R. (Children University Hospital, Brussels (Belgium))
Primary esophageal schwannomas are uncommon. We describe a case of a large asymptomatic primary esophageal schwannoma in a 65-year-old patient. Computed tomography and positron emission tomography revealed an (18)F-fluorodeoxyglucose-avid 11-cm mass arising from the esophagus. A preoperative diagnosis was made via endoscopic ultrasound. The patient underwent a three-field esophagogastrectomy with cervical esophagogastric anastomosis. He remains well and free of recurrence 10 months after treatment. PMID:22450109
Kassis, Edmund S; Bansal, Shelly; Perrino, Carmen; Walker, Jon P; Hitchcock, Charles; Ross, Patrick; Daniel, Vincent C
We report a rare case of a patient with esophageal carcinoma diagnosed using transthoracic echocardiography. This examination proved to be useful in the identification of a paracardiac mediastinal mass. Images of the esophageal carcinoma, of the stent in the esophagus, and the bubbles inside the stent generated with the ingestion of a carbonated beverage, have not been previously published. Therefore, we believe our findings may be useful to other echocardiographers. PMID:23834459
Cianciulli, Tomás F; Saccheri, María C; Lax, Jorge A; Bianchi, Ricardo A; Beck, Martín A; Ferreiro, Daniel E
Pancreatic adenocarcinoma is an important cause of death from cancer throughout the developed world. There are few established environmental risk factors, but a previous history of pancreatitis and exposure to tobacco and salted food appear to be the most important. A family history of pancreatic adenocarcinoma is not common in patients with this disease, but recent research has shown that
T Y Flanders; W D Foulkes
Background: We observed an endoscopic abnormality in a group of children with histological esophagitis. We termed this finding “vertical lines in esophageal mucosa” (VLEM). We examined the relationship between the presence of VLEM and significant histologic changes in esophageal mucosal biopsies. Methods: Between January 1, 1992, and August 31, 1994, the senior author (JFF) performed 255 esophageal biopsies. The procedure
Sandeep K. Gupta; Joseph F. Fitzgerald; Sonny K. F. Chong; Joseph M. Croffie; Margaret H. Collins
Esophageal atresia (EA) is a congenital developmental defect of the alimentary tract concerning the interruption of the esophagus with or without connection to the trachea. The incidence of EA is 1 in 3000-3500 of live-born infants, and occurs in both isolated and syndromic (in combination with abnormalities in other organ systems) forms. The molecular mechanisms underlying the development of EA are poorly understood. Knockout studies in mice indicate that genes like Sonic hedgehog, Gli2, and Gli3 play a role in the etiology of EA. These facts led us to hypothesize that Sonic hedgehog-GLI gene rearrangements are associated with EA in humans. To test this hypothesis, we screened patients with isolated and syndromic EA for GLI2 and/or GLI3 microrearrangements using methods to estimate the copy number (Multiplex Ligation-dependent Probe Amplification, real-time polymerase chain reaction). To our best knowledge this is the first study assessing copy number of GLI2 and GLI3 genes in patients with EA. PMID:23442119
Bednarczyk, D; Smigiel, R; Patkowski, D; Laczmanska, I; Lebioda, A; Laczmanski, L; Sasiadek, M M
Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient’s age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary.
Zakharova, Olga P; Karmazanovsky, Grigory G; Egorov, Viacheslav I
Mullerian tumors are extremely rare malignancies in the retroperitoneum. We report a case of a 46-year old woman who presented with an eight year history of lower abdominal mass. Ultrasonography (US) and computed tomography (CT) demonstrated a 15×10 cm cystic mass in the left lower retroperitoneum. As serial percutaneous needle aspiration cytology was negative for malignancy, she was observed for seven years. Eleven months ago, the mass was excised. The histopathology was reported as mucinous adenocarcinoma of the retroperitoneum. Six cycles of intraperitoneal (IP) chemotherapy was administered during the last six months after diagnosis of recurrence by aspiration cytology and high serum tumor markers (CEA, CA19-9). A few days ago, positron emission tomographic (PET) scanning showed evidence of local recurrence and single vertebral metastasis, so she was admitted again for systemic chemotherapy. Meticulous revision of additional sections of the tumor revealed papillary, serous, mucinous, and endometrioid subtypes of the mullerian adenocarcinoma. To our knowledge, there has been no similar case described in the literature.
Elnemr, Ayman; Yonemura, Yutaka; Shinbo, Masaya; Nishino, Eisei
Mullerian tumors are extremely rare malignancies in the retroperitoneum. We report a case of a 46-year old woman who presented with an eight year history of lower abdominal mass. Ultrasonography (US) and computed tomography (CT) demonstrated a 15×10 cm cystic mass in the left lower retroperitoneum. As serial percutaneous needle aspiration cytology was negative for malignancy, she was observed for seven years. Eleven months ago, the mass was excised. The histopathology was reported as mucinous adenocarcinoma of the retroperitoneum. Six cycles of intraperitoneal (IP) chemotherapy was administered during the last six months after diagnosis of recurrence by aspiration cytology and high serum tumor markers (CEA, CA19-9). A few days ago, positron emission tomographic (PET) scanning showed evidence of local recurrence and single vertebral metastasis, so she was admitted again for systemic chemotherapy. Meticulous revision of additional sections of the tumor revealed papillary, serous, mucinous, and endometrioid subtypes of the mullerian adenocarcinoma. To our knowledge, there has been no similar case described in the literature. PMID:21139951
Elnemr, Ayman; Yonemura, Yutaka; Shinbo, Masaya; Nishino, Eisei
MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2?-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors.
Jin, Zhe; Cheng, Yulan; Gao, Yan; Feng, Xianling; Dong, Ming; Cao, Ziyi; Chen, Si; Yu, Huimin; Zhao, Zhenfu; Zhang, Xiaojing; Liu, Jie; Mori, Yuriko; Fan, Xinmin; Meltzer, Stephen J.
...Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices Â§ 868.1910 Esophageal stethoscope. (a) Identification. An esophageal...
...Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices Â§ 868.5650 Esophageal obturator. (a) Identification. An esophageal...
We report a case of esophageal web demonstrated with sonography in a 45-year-old woman with dysphagia. The esophageal web was incidentally detected as a circumferential hypoechoic membrane on sonograms of the cervical esophagus. PMID:16547989
Rokade, Muktachand Laxman
...FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices Â§ 876.5365 Esophageal dilator. (a) Identification. An esophageal...
We recently reported on a new fetal rat model of esophageal atresia (EA) with tracheoesophageal fistula (TEF) induced by prenatal exposure to adriamycin (1.75 mg\\/kg i. p. injected daily to the pregnant dam from the 6th to 9th gestational days). With this treatment regime, many fetuses were resorbed and the number of associated malformations was very high. The present study
B. Qi; J. A. Diez-Pardo; C. Navarro; J. A. Tovar
AIM: To evaluate the association between xeroderma pigmentosum group D (XPD), genetic polymorphism Lys751Gln and esophageal cancer risk. METHODS: We searched PubMed up to September 1, 2010 to identify eligible studies. A total of 10 case-control studies including 2288 cases and 4096 controls were included in the meta-analysis. Statistical analysis was performed with Review Manage version 4.2. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS: The results suggested that there is no significant association between XPD Lys751Gln polymorphism and esophageal cancer susceptibility in the overall population. However, in subgroup analysis by histology type, a significant association was found between XPD Lys751Gln polymorphism and esophageal adenocarcinoma (for CC vs AA: OR = 1.25, 95% CI = 1.01-1.55, P = 0.05 for heterogeneity). CONCLUSION: Our meta-analysis suggested that XPD Lys751Gln polymorphism may be associated with increased risk of esophageal adenocarcinoma.
Yuan, Ling; Cui, Dan; Zhao, Er-Jiang; Jia, Chen-Zhi; Wang, Li-Dong; Lu, Wei-Quan
Background Many studies have been carried out to test the hypothesis that the NQO1 C609T polymorphism might be associated with the risk of esophageal cancer. However, the results are poorly consistent, partly due to genetic or other sources of heterogeneity. To investigate the association between this polymorphism and the risk of esophageal cancer, a meta-analysis was performed. Methods We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of association. The frequency of the putative risk allele in the controls was estimated by the inverse-variance method. Cochran’s Q statistic and the inconsistency index (I2) were used to check heterogeneity. Egger’s test and an inverted funnel plot were used to assess the publication bias. Results Our study included eight published case-control studies about the NQO1 C609T polymorphism and esophageal cancer, including a total of 1,217 esophageal cancer patients and 1,560 controls. Overall, a significant association was found between the NQO1 C609T variant and esophageal cancer under a recessive model (OR?=?1.647; 95% CI?=?1.233-2.200). Regarding histological type, more significant evidence was found for esophageal squamous cell carcinoma (ESCC) (OR?=?2.03; 95% CI?=?1.29-3.19) than esophageal adenocarcinoma (EAC) (OR?=?1.61; 95% CI?=?1.01-2.56) under a recessive model. Conclusions The meta-analysis suggests that the NQO1 C609T polymorphism considerably increases the risk of esophageal cancer.
The long-term effects of gastric banding on esophageal function are not well described. This report describes a 28-year-old woman who developed signs and symptoms of abnormal esophageal motility and lower esophageal sphincter hypotension after gastric banding for morbid obesity. The current literature addressing the effects of gastric banding on esophageal function in light of this case report is discussed. PMID:17509126
O'Rourke, R W; Deveney, C W; McConnell, D B; Wolfe, B M; Jobe, B A
Esophageal stents are important tools for palliative treatment of inoperable esophageal malignancies. With the development of multiple self-expandable stents, there are now several therapeutic options for managing benign and malignant esophageal diseases. This paper discusses the various types of esophageal stents currently available, indications for their placement, challenges and complications that gastroenterologists face when placing these stents, and some of the innovations that will become available in the near future.
Hong, Jinwha; Lam-Tsai, Yvette; Gress, Frank
The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms. PMID:16331610
Kang, Sokbom; Kim, Jae Weon; Kang, Gyeong Hoon; Lee, Sun; Park, Noh Hyun; Song, Yong Sang; Park, Sang Yoon; Kang, Soon Beom; Lee, Hyo Pyo
EA-BRACHI (Experimental Apparatus for Basic study of Radiation Chemistry with Heavy Ions) has been constructed at a vertical port of AVF cyclotron in TIARA (Takasaki Ion Accelerators for Advanced Radiation Application) facility. This apparatus is used for...
M. Taguchi H. Namba Y. Aoki R. Watanabe Y. Matsumoto
The objectives were to produce clinical local electroanesthesia (EA) of the extremities, and produce electrical spinal anesthesia in monkeys. A form of anesthesia of the hand which entailed very severe muscle spasm was produced. The anesthesia was judged ...
R. H. Smith
A review examined six consecutive cases of patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) who underwent cardiac surgery at the authors' institution between 2001 and 2011 for associated complex congenital heart diseases. All the patients had a normal karyotype and showed EA with distal TEF. In all cases, gastrostomy was the initial surgical intervention. Cardiac surgery was performed concurrently with gastrostomy for one patient who had a total anomalous pulmonary venous connection with pulmonary venous obstruction. For two patients with duct-dependent pulmonary circulation, EA/TEF was corrected in the neonatal period, and an aortopulmonary shunt operation was electively performed after the first month of life. For two patients with duct-dependent systemic circulation, repair of EA/TEF was performed concurrently with gastrostomy, followed by palliative cardiac surgery during the neonatal period. For another patient without duct-dependent circulation, repair of EA/TEF was performed in the neonatal period. No mortality occurred during a median follow-up period of 6.2 years. However, respiratory complications including severe tracheomalacia for two patients, recurrent episodes of respiratory infection for three patients, and severe gastroesophageal reflux for five patients caused considerable long-term morbidity. PMID:22639007
Hayashi, Taiyu; Inuzuka, Ryo; Shiozawa, Yusuke; Shindo, Takahiro; Shimizu, Nobutaka; Katori, Tatsuo
There has been a suggestion that esophageal atresia with tracheoesophageal fistula (EA/TEF) may be related to the occurrence of infectious disease in the population during the time of early gestation. There is therefore a need for further data on trends in incidence related to infectious diseases. Data on the occurrence of EA/TEF with and without additional congenital malformations may also be relevant. The British Columbia Health Surveillance Registry is population-based with excellent case ascertainment of birth defects, and data are available on the incidence of infectious diseases for B.C., allowing comparison of trends to be made. One hundred forty-nine cases of EA/TEF occurred among 534,834 consecutive livebirths during the period 1966-1980 for an incidence rate of 1/3,590. No significant (p less than 0.05) annual, seasonal or monthly incidence trends were observed. In addition, the occurrence of EA/TEF could not be correlated with the prior incidence of infectious hepatitis, rubella, salmonella, or rubeola. Fifty-five percent of individuals with EA/TEF had congenital malformations in other systems, most frequently cardiovascular, gastrointestinal, and genitourinary. Most individuals with additional congenital malformations had multiple system involvement. PMID:3424224
Fraser, C; Baird, P A; Sadovnick, A D
Ga-67 scanning has been used to evaluate esophageal carcinoma. It has demonstrated candidal infection in other body sites and, in one previous case, in the esophagus. The authors present a case of diffuse esophageal uptake of Ga-67 in esophageal candidiasis.
Rundback, J.H.; Goldfarb, C.R.; Ongseng, F. (Beth Israel Medical Center, New York, NY (USA))
Background: Esophageal replacement is associated with significant morbidity that may lead to operative interventions. This study reviews the management and outcome of children who underwent reoperation after esophageal replacement.Methods: Eighteen patients who underwent esophageal replacement from 1985 to 1997 were reviewed retrospectively. Ten patients underwent reoperation. Patient management, perioperative morbidity, and the dietary intake at follow-up were recorded for each
James C. Y Dunn; Eric W Fonkalsrud; Harry Applebaum; William W Shaw; James B Atkinson
An attempt is made to explore those aspects of the history of esophageal surgery relevant to pediatric practice. In some areas, the history is entirely focused on conditions of particular pediatric significance; esophageal atresia is a classic example of this group. In other areas there is considerable overlap, which varies in extent, with the history of esophageal surgery in adult.
N. A. Myers
Background. Armillaridin (AM) is isolated from Armillaria mellea. We examined the anticancer activity and radiosensitizing effect on human esophageal cancer cells. Methods. Human squamous cell carcinoma (CE81T/VGH and TE-2) and adenocarcinoma (BE-3 and SKGT-4) cell lines were cultured. The MTT assay was used for cell viability. The cell cycle was analyzed using propidium iodide staining. Mitochondrial transmembrane potential was measured by DiOC6(3) staining. The colony formation assay was performed for estimation of the radiation surviving fraction. Human CE81T/VGH xenografts were established for evaluation of therapeutic activity in vivo. Results. AM inhibited the viability of four human esophageal cancer cell lines with an estimated concentration of 50% inhibition (IC50) which was 3.4-6.9??M. AM induced a hypoploid cell population and morphological alterations typical of apoptosis in cells. This apoptosis induction was accompanied by a reduction of mitochondrial transmembrane potential. AM accumulated cell cycle at G2/M phase and enhanced the radiosensitivity in CE81T/VGH cells. In vivo, AM inhibited the growth of CE81T/VGH xenografts without significant impact on body weight and white blood cell counts. Conclusion. Armillaridin could inhibit growth and enhance radiosensitivity of human esophageal cancer cells. There might be potential to integrate AM with radiotherapy for esophageal cancer treatment. PMID:23864890
Chi, Chih-Wen; Chen, Chien-Chih; Chen, Yu-Jen
The aim of the study was to evaluate the expression of tumor suppressor genes p53, fragile histidine triad gene (FHIT), and an oncogene insulin-like growth factor 2 (IGF2) as prognostic markers in the etiology of esophageal cancer. Immunohistochemistry (IHC) was performed in 39 archival tissue samples of different esophageal pathologies for the three genes. Abnormal p53 expression was maximum in all the cases of squamous cell carcinoma, while IGF2 expression was enhanced in squamous cell carcinoma (81%), adenocarcinoma (100%), and dysplasia of squamous epithelium (75%) samples when compared with normals (50%). To our surprise, 75% of normal tissues did not show FHIT expression, which was also not seen in 40% of dysplasias of squamous epithelium, 33.3% of adenocarcinoma, and 41% of squamous cell carcinoma. To the best of our knowledge, this is the first study evaluating IGF2 by IHC, as well as, correlating it with the expression of the two tumor suppressor genes, p53 and FHIT, in esophageal tissue. p53 expression was threefold higher than normal in dysplasias of squamous epithelium and adenocarcinoma, while it was eightfold higher in squamous cell carcinoma. IGF2 expression was low in normal and dysplasia tissue but was increased 1.97-fold in both types of malignancy. FHIT and p53 expression were well correlated in squamous cell carcinoma, supporting the observation that FHIT regulates and stabilizes p53. Altered/lowered FHIT levels may be a result of exposure to various exogenous agents; however, this could not be assessed in the present study as it was carried out on archival samples. A larger prospective study is warranted to establish the role of exogenous factors in FHIT expression. PMID:21668571
Chava, S; Mohan, V; Shetty, P J; Manolla, M L; Vaidya, S; Khan, I A; Waseem, G L; Boddala, P; Ahuja, Y R; Hasan, Q
Esophageal atresia (EA) is one of the congenital neonatal anomalies whose immediate consequence for the newborn is the inability to feed. Most centers strive to minimize the effects of surgeries and subsequent postoperative complications such as esophageal strictures, respiratory problems, and gastrointestinal reflux on the child's ability or motivation to feed. Feeding difficulties in early infancy may not only interrupt maternal expectations of becoming providers of nutrition to their infants but may also influence the infant's development of sensory motor skills and parent-child relationships. Early involvement by a multidisciplinary team consisting of occupational therapist, nutritionist, and psychologist is an important addition to the surgical and medical team. The team assists in preparing mothers for feeding-related difficulties, providing anticipatory guidance to improve feeding abilities and relationships, especially for children with multiple surgical involvements and prolonged periods of non-oral feeding. PMID:23679033
Ramsay, M; Birnbaum, R
Mammaglobin (MGB) has been proposed as a sensitive and specific immunohistochemical marker for adenocarcinoma of the breast. The differential diagnosis of breast adenocarcinoma versus a gynecologic primary frequently arises. We performed a semiquantitative survey of MGB immunoreactivity in 26 benign gynecologic tissues (6 ectocervices, 9 endocervices, 11 endometria), 86 ovarian adenocarcinomas, 70 endometrial adenocarcinomas, and 10 endocervical adenocarcinomas. Among ovarian tumors, MGB was present in 40% of endometrioid carcinomas; 36%, serous carcinomas; 21%, clear cell carcinomas; and 6%, mucinous carcinomas. Among endometrial cancers, MGB reactivity was present in 57% of endometrioid carcinomas, but only 30% of serous carcinomas and 6% of clear cell carcinomas. MGB was absent in endocervical adenocarcinomas. Across all tumor types with positive staining, MGB was focal or patchy (ie, less than diffuse) in 50 of 57 cases. Using a scale of 0 to 3+, the only 3 tumors with 3+ MGB reactivity were all serous carcinomas (1 ovarian and 2 endometrial). There were no cases with diffuse 3+ MGB expression. On the other hand, diffuse 2+ MGB was seen in 4 cases: 1 endometrioid carcinoma of ovary, 1 serous carcinoma of ovary, and 2 clear cell carcinomas of ovary. In conclusion, a diagnostically significant proportion of gynecologic carcinomas are immunoreactive for MGB. Gynecologic primaries should be considered in the differential diagnosis of MGB-positive malignancies of unknown origin. PMID:23084633
Hagemann, Ian S; Pfeifer, John D; Cao, Dengfeng
Standard cytotoxic chemotherapy is effective for some cancers, but for many others, available treatments offer only a limited survival benefit. Lung adenocarcinoma is one such cancer, responsible for approximately half of lung cancer deaths each year. Development of targeted therapies is thought to hold the most promise for successfully treating this disease, but a targeted approach is dependent on understanding the genomic state of the tumor cells. Exon-directed sequencing of large numbers of lung adenocarcinoma tumor samples has provided an initial low-resolution image of the somatic mutation profile of these tumors. Such cancer sequencing studies have confirmed the high frequency of TP53 and KRAS mutations in lung adenocarcinoma, have found inactivating mutations in known tumor suppressor genes not previously associated with lung adenocarcinoma, and have identified oncogenic mutations of EGFR upon which the first targeted therapy for lung adenocarcinoma patients was based. Additional candidate oncogenes await functional validation. It is anticipated that upcoming whole-exome and whole-genome lung adenocarcinoma sequencing experiments will reveal a more detailed landscape of somatic mutations that can be exploited for therapeutic purposes.
Background We attempted to identify novel biomarkers and therapeutic targets for esophageal squamous cell carcinoma by gene expression profiling of frozen esophageal squamous carcinoma specimens and examined the functional relevance of a newly discovered marker gene, WDR66. Methods Laser capture microdissection technique was applied to collect the cells from well-defined tumor areas in collaboration with an experienced pathologist. Whole human gene expression profiling of frozen esophageal squamous carcinoma specimens (n?=?10) and normal esophageal squamous tissue (n?=?18) was performed using microarray technology. A gene encoding WDR66, WD repeat-containing protein 66 was significantly highly expressed in esophageal squamous carcinoma specimens. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in a second and independent cohort (n?=?71) consisting of esophageal squamous cell carcinoma (n?=?25), normal esophagus (n?=?11), esophageal adenocarcinoma (n?=?13), gastric adenocarcinoma (n?=?15) and colorectal cancers (n?=?7). In order to understand WDR66’s functional relevance siRNA-mediated knockdown was performed in a human esophageal squamous cell carcinoma cell line, KYSE520 and the effects of this treatment were then checked by another microarray analysis. Results High WDR66 expression was significantly associated with poor overall survival (P?=?0.031) of patients suffering from esophageal squamous carcinomas. Multivariate Cox regression analysis revealed that WDR66 expression remained an independent prognostic factor (P?=?0.042). WDR66 knockdown by RNA interference resulted particularly in changes of the expression of membrane components. Expression of vimentin was down regulated in WDR66 knockdown cells while that of the tight junction protein occludin was markedly up regulated. Furthermore, siRNA-mediated knockdown of WDR66 resulted in suppression of cell growth and reduced cell motility. Conclusions WDR66 might be a useful biomarker for risk stratification of esophageal squamous carcinomas. WDR66 expression is likely to play an important role in esophageal squamous cell carcinoma growth and invasion as a positive modulator of epithelial-mesenchymal transition. Furthermore, due to its high expression and possible functional relevance, WDR66 might be a novel drug target for the treatment of squamous carcinoma.
Abnormalities of the esophagus are common, and complications associated with these disorders and diseases can involve the mediastinum, tracheobronchial tree, and lungs. The most common complications include mediastinitis secondary to esophageal perforation or postoperative anastomotic leak, or both; empyema due to fistula formation; and aspiration pneumonia. The authors reviewed the radiologic appearances of those and other common thoracic complications associated with esophageal disorders to facilitate early detection, diagnosis, and management. Computed tomographic (CT) findings of acute mediastinitis secondary to esophageal perforation may include esophageal thickening, extraluminal gas, pleural effusion, single or multiple abscesses, and extraluminal contrast medium. The radiologic manifestations of pneumonia secondary to tracheoesophageal fistula are variable, depending on the spread and severity of the aspiration. The most common radiographic pattern is that of bronchopneumonia with scattered air-space opacities. CT has been regarded as the imaging modality of choice for the evaluation of suspected esophagopleural fistula, because the site of communication between the pleural space and the esophagus can often be seen. An awareness of the radiologic manifestations of these complications is thus required to facilitate early diagnosis. PMID:12376614
Giménez, Ana; Franquet, Tomás; Erasmus, Jeremy J; Martínez, Santiago; Estrada, Pilar
Celiac disease (CD) may often be associated with various motor disorders affecting the different segments of the digestive tract, including the esophagus. Although it has not been universally reported, some available evidences indicate that pediatric and adult celiac patients could manifest a higher frequency of esophagitis and gastroesophageal reflux disease-related symptoms compared to nonceliac patients. In addition, several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence. Since the participation of gluten in the esophageal symptoms of CD seems clear, its intimate mechanisms have yet to be elucidated, and several hypothesis have been proposed, including the specific immune alterations characterizing CD, the reduction in nutrient absorption determining the arrival of intact gluten to distal gastrointestinal segments, and various dysregulations in the function of gastrointestinal hormones and peptides. Recent studies have suggested the existence of a possible relationship between CD and eosinophilic esophagitis, which should be more deeply investigated. PMID:21438963
Lucendo, A J
INTRODUCTION The risk of periampullary neoplasia in patients with familial adenomatous polyposis (FAP) is significantly increased compared to the general population. PRESENTATION OF CASE We herein report the case of a 47-year-old woman with classic familial adenomatous polyposis with a history of total proctocolectomy for FAP who presented with an ulcerous ampullary lesion 8 years after primary colorectal surgery. Interestingly, the patient had not enrolled to optimal postoperative upper endoscopy follow-up. The patient underwent a Whipple procedure. Histology demonstrated a T2N0 ampullary adenocarcinoma. DISCUSSION Periampullary disease in patients with familial adenomatous polyposis occurs increasingly, especially in the subset of patients without proper endoscopic follow-up. Current recommendations concerning upper endoscopy and appropriate management are herein discussed; the importance of optimal postoperative endoscopy after total proctocolectomy in the FAP setting is discussed. CONCLUSION Periampullary cancer carries a significant risk in patients with FAP and proper endoscopic follow-up should be applied in this special patient group in order to manage ampullary manifestations of the disease in a timely manner.
Mantas, Dimitrios; Charalampoudis, Petros; Nikiteas, Nikolaos
Objective To determine the prevalence of occult cervical nodal metastases in patients with squamous cell cancer and adenocarcinoma of the esophagus, and to determine the impact of esophagectomy with three-field lymph node dissection on survival and recurrence rates. Summary Background Data Although esophagectomy with three-field lymph node dissection is commonly practiced in Japan, its role in the surgical management of esophageal cancer in the United States, especially in patients with esophageal adenocarcinoma, is essentially unknown. Methods This is a prospective observational study of esophagectomy with three-field lymphadenectomy. Eighty patients underwent resection between August 1994 and April 2001. Clinicopathological information and follow-up data were collected on all patients until death or June 2001. Results Hospital mortality and morbidity rates were 5% and 46%, respectively. Metastases to the recurrent laryngeal and/or deep cervical nodes occurred in 36% of patients irrespective of cell type (adenocarcinoma 37%, squamous 34%) or location within the esophagus (lower third 32%, middle third 60%). Overall 5-year and disease-free survival rates were 51% and 46%, respectively. Sixty-nine percent presented with nodal metastases. The 5-year survival rate for node-negative patients was 88%; that for those with nodal metastases was 33%. The 5-year survival rate in patients with positive cervical nodes was 25% (squamous 40%, adenocarcinoma 15%). Conclusions Esophagectomy with three-field lymph node dissection can be performed with a low mortality and reasonable morbidity. Unsuspected metastases to the recurrent laryngeal and/or cervical nodes are present in 36% of patients regardless of cell type or location within the esophagus. Thirty percent of patients were upstaged, mainly from stage III to stage IV. An overall 5-year survival rate of 51% suggests a true survival benefit beyond that achieved solely on the basis of stage migration.
Altorki, Nasser; Kent, Michael; Ferrara, Cathy; Port, Jeffrey
The Barrett's Esophagus Translational Research Network (BETRNet) has been proposed to reduce the incidence, morbidity, and mortality of esophageal adenocarcinoma (EA), through answering key questions related to the progression of this disease, especially in the premalignant stage.
AIM: To evaluate the effects of indomethacin [dual cyclooxygenase (COX)-1/COX-2 inhibitor] and 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl) phenyl)-2-(5H)-furanone (MF-tricyclic) (COX-2 selective inhibitor) in a rat experimental model of Barrett’s esophagus and esophageal adenocarcinoma. METHODS: A total of 112 surviving post-surgery rats were randomly divided into three groups: the control group (n = 48), which did not receive any treatment; the indomethacin group (n = 32), which were given 2 mg/kg per day of the COX-1/COX-2 inhibitor; and the MF-tricyclic group (n = 32), which received 10 mg/kg per day of the selective COX-2 inhibitor. Randomly selected rats were killed either 8 wk or 16 wk after surgery. The timing of the deaths was in accordance with a previous study performed in our group. Only rats that were killed at the times designated by the protocol were included in the study. We then assessed the histology and prostaglandin E2 (PGE2) expression levels in the rat esophagi. An additional group of eight animals that did not undergo esophagojejunostomy were included in order to obtain normal esophageal tissue as a control. RESULTS: Compared to a control group with no treatment (vehicle-treated rats), indomethacin treatment was associated with decreases in ulcerated esophageal mucosa (16% vs 35% and 14% vs 17%, 2 mo and 4 mo after surgery, respectively; P = 0.021), length of intestinal metaplasia in continuity with anastomosis (2 ± 1.17 mm vs 2.29 ± 0.75 mm and 1.25 ± 0.42 mm vs 3.5 ± 1.54 mm, 2 mo and 4 mo after surgery, respectively; P = 0.007), presence of intestinal metaplasia beyond anastomosis (20% vs 71.4% and 0% vs 60%, 2 mo and 4 mo after surgery, respectively; P = 0.009), severity of dysplasia (0% vs 71.4% and 20% vs 85.7% high-grade dysplasia, 2 mo and 4 mo after surgery, respectively; P = 0.002), and adenocarcinoma incidence (0% vs 57.1% and 0% vs 60%, 2 mo and 4 mo after surgery, respectively; P < 0.0001). Treatment with the selective COX-2 inhibitor, MF-tricyclic, did not prevent development of intestinal metaplasia or adenocarcinoma. In parallel, we observed a significant decrease in PGE2 levels in indomethacin-treated rats, but not in those treated with MF-tricyclic, at both 2 mo and 4 mo. Compared to control rats that did not undergo surgery (68 ± 8 ng/g, P = 0.0022 Kruskal-Wallis test) there was a significant increase in PGE2 levels in the esophageal tissue of the rats that underwent surgery either 2 mo (1332 ± 656 ng/g) or 4 mo (1121 ± 1015 ng/g) after esophagojejunostomy. However, no differences were found when esophageal PGE2 levels were compared 2 mo vs 4 mo post-esophagojejunostomy. At both the 2- and 4-mo timepoints, we observed a significant decrease in PGE2 levels in indomethacin-treated rat esophagi compared to those in either the control or MF-tricyclic groups (P = 0.049 and P = 0.017, respectively). No differences in PGE2 levels were found when we compared levels in rats treated with MF-tricyclic to not-treated rats. CONCLUSION: In this rat model of gastrointestinal reflux, indomethacin was associated with a decrease in the severity of esophagitis and reduced development of esophageal intestinal metaplasia and adenocarcinoma.
Esquivias, Paula; Morandeira, Antonio; Escartin, Alfredo; Cebrian, Carmelo; Santander, Sonia; Esteva, Francisco; Garcia-Gonzalez, Maria Asuncion; Ortego, Javier; Lanas, Angel; Piazuelo, Elena
Ellagic acid (EA), a naturally occurring plant polyphenol possesses broad chemoprotective properties. Dietary EA has been shown to reduce the incidence of N-2-fluorenylacetamide-induced hepatocarcinogenesis in rats and N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumors. In this study changes in the expression and activities of specific rat hepatic and esophageal mucosal cytochromes P450 (P450) and phase II enzymes following dietary EA treatment were investigated. Liver and esophageal mucosal microsomes and cytosol were prepared from three groups of Fisher 344 rats which were fed an AIN-76 diet containing no EA or 0.4 or 4.0 g/kg EA for 23 days. In the liver total P450 content decreased by up to 25% and P450 2E1-catalyzed p-nitrophenol hydroxylation decreased by 15%. No changes were observed in P450 1A1, 2B1 or 3A1/2 expression or activities or cytochrome b5 activity. P450 reductase activity decreased by up to 28%. Microsomal epoxide hydrolase (mEH) expression decreased by up to 85% after EA treatment, but mEH activities did not change. The hepatic phase II enzymes glutathione S-transferase (GST), NAD(P)H:quinone reductase [NAD-(P)H:QR] and UDP glucuronosyltransferase (UDPGT) activities increased by up to 26, 17 and 75% respectively. Assays for specific forms of GST indicated marked increases in the activities of isozymes 2-2 (190%), 4-4 (150%) and 5-5 (82%). In the rat esophageal mucosa only P450 1A1 could be detected by Western blot analysis and androstendione was the only P450 metabolite of testosterone detectable. However, there were no differences in the expression of P450 1A1, the formation of androstendione or NAD(P)H:QR activities between control and EA-fed rats in the esophagus. Although there was no significant decrease in overall GST activity, as measured with 1-chloro-2,4-dinitrobenzene (CDNB), there was a significant decrease in the activity of the 2-2 isozyme (66% of control). In vitro incubations showed that EA at a concentration of 100 microM inhibited P450 2E1, 1A1 and 2B1 activities by 87, 55 and 18% respectively, but did not affect 3A1/2 activity. Using standard steady-state kinetic analyses, EA was shown to be a potent non-competitive inhibitor of both liver microsomal ethoxyresorufin O-deethylase and p-nitrophenol hydroxylase activities, with apparent Ki values of approximately 55 and 14 microM respectively. In conclusion, these results demonstrate that EA causes a decrease in total hepatic P450 with a significant effect on hepatic P450 2E1, increases some hepatic phase II enzyme activities [GST, NAD-(P)H:QR and UDPGT] and decreases hepatic mEH expression. It also inhibits the catalytic activity of some P450 isozymes in vitro. Thus the chemoprotective effect of EA against various chemically induced cancers may involve decreases in the rates of metabolism of these carcinogens by phase I enzymes, due to both direct inhibition of catalytic activity and modulation of gene expression, in addition to effects on the expression of phase II enzymes, thereby enhancing the ability of the target tissues to detoxify the reactive intermediates. PMID:8625497
Ahn, D; Putt, D; Kresty, L; Stoner, G D; Fromm, D; Hollenberg, P F
We recently reported that esophageal contraction reduces esophageal wall perfusion in an animal study. Our aim was to determine esophageal wall blood perfusion (EWBP) during esophageal contraction and transient lower esophageal sphincter relaxations (TLESRs) in humans. We studied 12 healthy volunteers. A custom-designed laser Doppler probe was anchored to the esophageal wall, 4–6 cm above the LES, by use of the Bravo pH system so that the laser light beam stay directed toward the esophageal mucosa. A high-resolution manometry equipped with impedance electrodes recorded esophageal pressures and reflux events. Synchronized pressure, impedance, pH, and EWBP recordings were obtained during dry and wet swallows and following a meal. Stable recordings of laser Doppler EWBP were only recorded when the laser Doppler probe was firmly anchored to the esophageal wall. Esophageal contractions induced by dry and wet swallows resulted in 46 ± 9% and 60 ± 10% reduction in the EWBP, respectively (compared to baseline). Reduction in EWBP was directly related to the amplitude (curvilinear fit) and duration of esophageal contraction. Atropine reduced the esophageal contraction amplitude and decreased the EWBP reduction associated with esophageal contraction. TLESRs were also associated with reduction in the EWBP, albeit of smaller amplitude (29 ± 3%) but longer duration (19 ± 2 s) compared with swallow-induced esophageal contractions. We report 1) an innovative technique to record EWBP for extended time periods in humans and 2) contraction of circular and longitudinal muscle during peristalsis and selective longitudinal muscle contraction during TLESR causes reduction in the EWBP; 3) using our innovative technique, future studies may determine whether esophageal wall ischemia is the cause of esophageal pain/heartburn.
Jiang, Yanfen; Bhargava, Valmik; Kim, Young Sun
Barrett's esophagus (BE) is metaplastic columnar epithelium converted from normal squamous epithelia in the distal esophagus that is thought to be a precancerous lesion of esophageal adenocarcinoma. BE is attributed to gastroesophageal reflux disease (GERD), and therefore gastric acid or bile acids are thought to be factors that cause epithelial cell damage and inflammation in the gastro-esophageal junction. The decrease of adherent junction molecules, E-cadherin has been reported to be associated with the progression of the Barrett's carcinoma, but the initiation of BE is not sufficiently understood. BE is characterized by the presence of goblet cells and occasionally Paneth cells are observed at the base of the crypts. The Paneth cells possess dense granules, in which human antimicrobial peptide human defensin-5 (HD-5) are stored and secreted out of the cells. This study determined the roles of HD-5 produced from metaplastic Paneth cells against adjacent to squamous cells in the gastro-esophageal junction. A human squamous cell line Het-1A, was incubated with the synthetic HD-5 peptide as a model of squamous cell in the gastro-esophageal junctions, and alterations of E-cadherin were investigated. Immunocytochemistry, flowcytometry, and Western blotting showed that the expression of E-cadherin protein was decreased. And a partial recovery from the decrease was observed by treatment with a CD10/neprilysin inhibitor (thiorphan). In conclusion, E-cadherin expression in squamous cells was reduced by HD-5 using in vitro experiments. In gastro-esophageal junction, HD-5 produced from metaplastic Paneth cells may therefore accelerate the initiation of BE. PMID:23958301
Nomura, Yoshiki; Tanabe, Hiroki; Moriichi, Kentaro; Igawa, Satomi; Ando, Katsuyoshi; Ueno, Nobuhiro; Kashima, Shin; Tominaga, Motoya; Goto, Takuma; Inaba, Yuhei; Ito, Takahiro; Ishida-Yamamoto, Akemi; Fujiya, Mikihiro; Kohgo, Yutaka
AIM: To clarify the association between Helicobacter pylori (H. pylori) infection and the risk of esophageal carcinoma through a meta-analysis of published data. METHODS: Studies which reported the association between H. pylori infection and esophageal cancer published up to June 2013 were included. The odds ratios (ORs) and corresponding 95%CIs of H. pylori infection on esophageal cancer with respect to health control groups were evaluated. Data were extracted independently by two investigators and discrepancies were resolved by discussion with a third investigator. The statistical software, STATA (version 12.0), was applied to investigate heterogeneity among individual studies and to summarize the studies. A meta-analysis was performed using a fixed-effect or random-effect method, depending on the absence or presence of significant heterogeneity. RESULTS: No significant association between H. pylori infection and esophageal squamous cell carcinoma (ESCC) risk was found in the pooled overall population (OR = 0.97, 95%CI: 0.76-1.24). However, significant associations between H. pylori infection and ESCC risk were found in Eastern subjects (OR = 0.66, 95%CI: 0.43-0.89). Similarly, cytotoxin-associated gene-A (CagA) positive strains of infection may decrease the risk of ESCC in Eastern subjects (OR = 0.77, 95%CI: 0.65-0.92), however, these associations were not statistically significant in Western subjects (OR = 1.26, 95%CI: 0.97-1.63). For esophageal adenocarcinoma (EAC) the summary OR for H. pylori infection and CagA positive strains of infection were 0.59 (95%CI: 0.51-0.68) and 0.56 (95%CI: 0.45-0.70), respectively. CONCLUSION: H. pylori infection is associated with a decreased risk of ESCC in Eastern populations and a decreased risk of EAC in the overall population.
Xie, Fa-Jun; Zhang, Yi-Ping; Zheng, Qiu-Qing; Jin, Hong-Chuan; Wang, Fa-Liang; Chen, Ming; Shao, Lan; Zou, De-Hong; Yu, Xin-Min; Mao, Wei-Min
Background: Primary eosinophilic esophagitis, a chronic inflammatory disorder of the esophagus, evokes recurrent dysphagia. Endoscopy is often unremarkable, and no consensus exists regarding management of resultant dysphagia. The response of a series of patients with primary eosinophilic esophagitis to dilation is reported together with a description of a possibly pathognomonic sign: fragile esophageal mucosa, for which the term “crępe-paper” mucosa
Alex Straumann; Livio Rossi; Hans-Uwe Simon; Pius Heer; Hans-Peter Spichtin; Christoph Beglinger
Benign esophagorespiratory fistula is a rare but often lethal affection and difficult to cure. Possible treatments are surgery or esophageal stenting but may fail and cause respiratory failure. Two patients with spontaneous esophagorespiratory fistula after chemoradiotherapy for an esophageal malignancy were both treated by esophageal exclusion but esophageal stent were left in place. The esophageal stents were transtracheally removed through the fistula. The removals were successful, patients could leave Intensive Care Unit and returned home. Transtracheal esophageal stent removal is technically possible but very risky. Such situations must be avoided: esophageal stents must absolutely be removed before esophageal exclusion.
Buiret, Guillaume; Guiraud, Michel; Pierron, Jerome; Schoeffler, Mathieu; Duperret, Serge; Baulieux, Jacques; Wander, Lionel; Poupart, Marc; Pignat, Jean-Christian
Surgery is an essential part of the treatment of patients with esophageal carcinoma. However, there is no consensus on whether the surgical technique can be improved to promote better survival outcome. Specifically, the real value of the addition of a radical lymphadenectomy to the esophageal resection is still elusive and controversial. This paper focuses on the debate of esophagectomy and lymphadenectomy for the treatment of esophageal cancer. PMID:23553174
Herbella, Fernando A M; Laurino Neto, Rafael M; Allaix, Marco E; Patti, Marco G
\\u000a Esophageal carcinoma is an uncommon gastrointestinal malignancy with a prevalence rate which is far less than the more common\\u000a colo-rectal cancers. Whereas the overall incidence of esophageal cancer has risen only gradually with time, in the United\\u000a States, Canada, and Western Europe, there has been a dramatic change in the distribution of esophageal cancer by cell type\\u000a (figure 1). Currently
f. Richard; m. d. Heitmiller
Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal nociceptors. Whole cell perforated patch-clamp recordings and single-cell RT-PCR analysis were performed on the primary afferent neurons retrogradely labeled from the esophagus in the guinea pig. Extracellular recordings were made from the isolated innervated esophagus. In patch-clamp studies, adenosine evoked activation (inward current) in a majority of putative nociceptive (capsaicin-sensitive) vagal nodose, vagal jugular, and spinal dorsal root ganglia (DRG) neurons innervating the esophagus. Single-cell RT-PCR analysis indicated that the majority of the putative nociceptive (transient receptor potential V1-positive) neurons innervating the esophagus express the adenosine receptors. The neural crest-derived (spinal DRG and vagal jugular) esophageal nociceptors expressed predominantly the adenosine A1 receptor while the placodes-derived vagal nodose nociceptors expressed the adenosine A1 and/or A2A receptors. Consistent with the studies in the cell bodies, adenosine evoked activation (overt action potential discharge) in esophageal nociceptive nerve terminals. Furthermore, the neural crest-derived jugular nociceptors were activated by the selective A1 receptor agonist CCPA, and the placodes-derived nodose nociceptors were activated by CCPA and/or the selective adenosine A2A receptor CGS-21680. In contrast to esophageal nociceptors, adenosine failed to stimulate the vagal esophageal low-threshold (tension) mechanosensors. We conclude that adenosine selectively activates esophageal nociceptors. Our data indicate that the esophageal neural crest-derived nociceptors can be activated via the adenosine A1 receptor while the placodes-derived esophageal nociceptors can be activated via A1 and/or A2A receptors. Direct activation of esophageal nociceptors via adenosine receptors may contribute to the symptoms in esophageal diseases.
Ru, F.; Surdenikova, L.; Brozmanova, M.
Background. The association of congenital stenosis of the distal esophagus (CES) in children with esophageal atresia\\/tracheoesophageal\\u000a fistula complex (TEF) has been described but is thought to be rare. Most reports have been of individual or small numbers\\u000a of cases. Objective. The objective of the study was to evaluate the incidence, clinical and radiographic features of CES associated with TEF,\\u000a and
Beverley Newman; Thomas M. Bender
Background Studies of positron emission tomography (PET) have focused mainly on tumor staging. The role of PET in predicting survival\\u000a has received less attention. We sought to assess the relationship of pretreatment maximum standard uptake value (SUVmax) to survival in surgical patients with esophageal cancer.\\u000a \\u000a \\u000a \\u000a Methods The study consisted of 72 esophagectomy patients (60 with adenocarcinoma) undergoing resection between July 2005 and
Boris Sepesi; Daniel P. Raymond; Marek Polomsky; Thomas J. Watson; Virginia R. Litle; Carolyn E. Jones; Rui Hu; Xing Qiu; Jeffrey H. Peters
Eosinophilic esophagitis (EE) is a rarely diagnosed condition involving eosinophilic infiltration of the esophageal mucosa. Here we present a case of EE in a 69-year-old Japanese man, who presented with abdominal pain, appetite loss, and a history of bronchial asthma. Laboratory findings included peripheral eosinophilia and an increased serum immunoglobulin E level. Computed tomography showed diffuse severe thickening of the esophageal wall, and a barium esophagogram revealed a small caliber of the middle and lower portion of the esophagus, without normal peristaltic contractions. Endoscopy of the esophagus showed a pale mucosa, with adherent whitish exudates resembling fungal infection, and prominent ring-like contractions. Histologic examination of a biopsy specimen revealed marked eosinophil infiltration into the esophageal mucosa. Endoscopic ultrasonography (EUS) demonstrated marked circumferential thickening of the esophageal submucosal layer, and an esophageal manometry study showed a high percentage of ineffective esophageal peristalsis and high-amplitude esophageal body contractions. EUS findings showed no change even after oral corticosteroid therapy, although the histological findings were improved. This is thought to be the first documented Japanese case of EE. EE should be considered in the differential diagnosis in cases of esophageal motility disturbance, even if the patients do not complain of dysphagia. PMID:16933010
Furuta, Koichiro; Adachi, Kyoichi; Kowari, Kentaro; Mishima, Yuko; Imaoka, Hiroshi; Kadota, Chikara; Koshino, Kenji; Miyake, Tatsuya; Kadowaki, Yasunori; Furuta, Kenji; Kazumori, Hideaki; Sato, Shuichi; Ishihara, Shunji; Amano, Yuji; Honda, Masaaki; Kinoshita, Yoshikazu
Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients, and approximately 5–15% of cirrhosis patients show newly formed varices or worsening of varices each year. The major therapeutic strategy of esophageal varices consists of primary prevention, treatment for bleeding varices, and secondary prevention, which are provided by pharmacological, endoscopic, interventional and surgical treatments. Optimal management of esophageal varices requires a clear understanding of the pathophysiology and natural history. In this paper, we outline the current knowledge and future prospect in the pathophysiology of esophageal varices and portal hypertension.
Maruyama, Hitoshi; Yokosuka, Osamu
The use of sentinel node surgery for esophageal carcinoma is still under investigation. We evaluated the data available in the literature on this topic, and herein present the results in a systematic review format. PUBMED, SCOPUS, the ISI web of knowledge and the information from the annual meetings of the Japan Esophageal Society were searched using the search terms: "(esophagus OR esophageal) AND sentinel". The outcomes of interest were the detection rate and sensitivity. Overall, 18 studies were included. The pooled detection rate was 89.2 % [82.6-93.5]. Patients with T1 and two tumors had a 17 % higher detection rate compared to those with T3 and four tumors. The pooled sensitivity was 84 % [78-88 %]. The sensitivity was higher for adenocarcinoma compared to squamous cell carcinoma (SCC) (91 vs. 81 %). In the SCC patients, there was a trend toward decreased sensitivity associated with an increasing tumor depth (T1:88 %, T2:76 %, T3:50 %). Our analysis indicated that sentinel node biopsy is useful in adenocarcinoma patients. For SCC patients, including only cN0 patients (preferably T1 and 2) would increase the detection rate and sensitivity. Due to the limited number of high-quality studies, drawing any more definite conclusions is impossible. Large cohort studies with a standardized and consistent design will be needed in the future. PMID:23715926
Dabbagh Kakhki, Vahid Reza; Bagheri, Reza; Tehranian, Shahrzad; Shojaei, Pardis; Gholami, Hassan; Sadeghi, Ramin; Krag, David N
The aim of this paper is to evaluate the methods and therapeutic principles of esophageal diverticula pathology. We analyze the main pathological mechanisms which establish the therapeutic attitude linked with a complex pretherapeutic evaluation. In our study we enrolled 12 patients operated between 2001-2009 for esophageal diverticula with different topography. In this period of time there were much more patients diagnosed with this pathology, but the need for surgery was establish very tight regarding the actual practical guide which impose the identification and interception of physiological mechanisms by the surgical procedure. We highlight the particular technical details, as well as the important differences of postoperatory complications according to the topography of the diverticula pouch. PMID:21523958
Constantinoiu, S; Constantin, A; Predescu, D; Mates, I N; Mocanu, A; Gheorghe, M; Hoar?, P; Achim, F; Cociu, L
Esophageal cancer remains one of the leading causes of cancer death worldwide. Patients generally present with progressive\\u000a dysphagia, malnutrition, and weight loss. The diagnosis commonly involves radiologic studies and conventional esophagogastroduodenoscopy.\\u000a Advances in endoscopic evaluation have allowed early detection of premalignant and malignant lesions. These techniques include\\u000a chromoscopy, which can be performed in conjunction with high-resolution\\/magnification endoscopy, and fluorescent endoscopy.
Darius Sorbi; David E. Fleischer
Objective: Symptoms of pediatric eosinophilic esophagitis (EoE) include dysphagia, emesis, regurgitation and feeding difficulties. This symptom complex has been mistaken for refractory gastroesophageal reflux disease (GERD). Whether EoE and GERD are related is controversial. Recently, EoE has been associated with upper airway manifestations including recurrent sinusitis, cough, wheezing, pneumonia, laryngeal edema, and subglottic stenosis. Laryngospasm secondary to EoE has not
Carrie L. Francis; Troy Gibbons; Gresham T. Richter
Eosinophilic esophagitis (EE) is a newly recognized disease, which has largely been called idiopathic EE, emphasizing the poor understanding of its pathogenesis. EE is a severe disease of the esophagus characterized by an accumulation of eosinophils in the esophageal mucosa. EE is highly associated with atopic disease and emerging evidence suggests a primary role for food antigen sensitization in disease etiology. Nevertheless, the nomenclature “Eosinophilic esophagitis” describes only the surface of the iceberg of a complex disorder. Epithelial cells, fibroblasts, endothelial cells and smooth muscles cells are involved in pathologic features of the disease and numerous leukocyte subtypes are recruited (eosinophils, mast cells, lymphocytes). As such, the pathogenesis of EE involves multiple tissues, cell types, genes and derives from complex genetic and environmental factors. “Pathogenesis” is a fusion of two Greek words pathos (disease) and genesis (development). In this review, we aim to define the fundamental piece of knowledge available today that characterizes the mechanisms by which certain etiological factors cause EE, reviewing human studies, murine models and recent knowledge regarding the involvement of environmental, cellular, molecular and genetic factors in the development of EE.
Blanchard, Carine; Rothenberg, Marc E.
Selective catherization of the left gastric vein was performed after percutaneous transhepatic portography (PTP) in patients with portal hypertension and esophageal varices. Following the hypothesis that drugs increasing the lower esophageal sphincter (LES) pressure may obstruct the variceal blood flow throught the lower esophagus, the effect of different drugs (i.e., intravenous injection of vasopressin, pentagastrin, domperidone and somatostatin and subcutaneous injection of metacholine) on the variceal blood flow was examined. Vasopressin did not change the variceal blood flow; pentagastrine, with its known effect of increasing the LES pressure produced a total interruption of the flow in four of eight patients; domperiodone, also known to increase the LES pressure obstructed the variceal blood flow in the only patient examined with this drug; somatostatin has no reported action on the LES but blocked the flow in one of two patients; and metacholine, reported to increase the LES pressure did not produce any change in the flow in the three patients examined. LES pressure was recorded before and during vasopressin infusion in seven patients with portal hypertension and esophageal varices. No reaction on the pressure was found. The patient number in the study is small and the results are nonuniform but still they suggest that drugs increasing the LES tonus might be useful to control variceal blood flow.
Lunderquist, A.; Owman, T.; Alwmark, A.; Gullstrand, P.; Hall-Angeras, M.; Joelsson, B.; Tranberg, K.G.; Pettersson, K.I.
A case of primary adenocarcinoma in appendiceal diverticulosis is reported. Such a case has never been mentioned before in the literature. It was not possible to diagnose the case preoperatively. This emphasizes the importance of histological examination of all appendiceal samples. PMID:10850196
Thomsen, J B; al-Suliman, N; Kĺg, L; Lindebjerg, J
Plasmacytoid adenocarcinoma of the lung has not been reported. Herein reported is the first case of plasmacytoid adenocarcinoma of the lung. A 68-year-old man presented with cough and sputum. X-P and CT demonstrated a large tumor (10 x 10 x 9 cm) in the right upper lobe. CT-guided needle biopsy was performed. The biopsy showed plasmacytoid malignant cells. The malignant cells were small, had eccentrically located nuclei, perinuclear halo, and basophilic cytoplasm. No mucins were observed by mucins stains. Immunohistochemical study showed that the tumor cells were positive for pancytokeratin AE1/3, pancytokeratin CAM5.2, TTF-1, Ki-67 (labeling 70%), CA19-9, and p53. They were negative for neuron specific enolase, CEA, CD45, CD68, chromogranin, synaptophysin, surfactant apoprotein A, CDX-2, ?-chain, ?-chain, KIT, and PDGFRA. Since epithelial markers and adenocarcinoma markers were positive, the pathological diagnosis was plasmacytoid adenocarcinoma of lung. The patient is now treated with chemotherapy. PMID:22670180
Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of
Ikuo Hirano; Joel E. Richter
There have so far been few reports on esophageal diverticulum in children. We experienced two symptomatic pediatric cases with esophageal diverticulum. Our cases manifested high fever and dysphagia with chest pain during swallowing. The patients underwent endoscopic diverticulotomy. The septum between the diverticulum and the esophagus was cut using the argon plasma coagulation (APC 3000) system. We recommend an endoscopic diverticulotomy
Y. Nishimoto; T. Taguchi; K. Ogita; M. Hashizume; S. Suita
Gastro-esophageal reflux disease encompasses a spectrum of disorders in which gastric reflux leads to symptoms and\\/or damage to the esophageal mucosa. Although a common problem in clinical practice, our understanding of the pathophysiology of the condition has not been matched by our knowledge of its epidemiology and natural history. This review examines some of the difficulties inherent in epidemiological studies
P. J. Howard; R. C. Heading
Eosinophilic esophagitis is a chronic, clinically and histologically defined, inflammatory condition of the esophagus. The histological hallmark of eosinophilic esophagitis is a relevant, often patchy infiltration of the esophageal mucosa with eosinophils. In a consensus report a threshold value of approximately 120 eosinophils per mm(2) was arbitrarily fixed as a diagnostic criterion. Noteworthy for the quantification of the eosinophilic infiltration are several technical facts, for instance size and covering extent of the biopsy specimen of the high-power field (hpf) and quality of embedding of biopsy specimens have to be considered. In order to establish the histological diagnosis several additional abnormalities must be included in the assessment and gastrointestinal reflux disease is the main differential diagnosis of eosinophilic esophagitis. Finally it is emphasized that for an affirmative diagnosis of eosinophilic esophagitis, in addition to the histological findings the clinical facts must be included. PMID:23483314
Bussmann, C; Straumann, A
Overexpression of the mucin-type sialoglycoprotein podoplanin in cancer associated fibroblasts (CAFs) was recently shown to be associated with tumor progression, metastasis and poor prognosis in lung and breast cancer. Here we investigate the role of podoplanin expressing CAFs in esophagal adenocarcinoma (AC), its precursor lesions and metastases. Podoplanin expression was investigated immunohistochemically in 200 formalin-fixed, paraffin embedded specimens of invasive esophagal ACs, their corresponding metastases and 35 precursor lesions. Podoplanin expressing CAFs (CAF+) were observed in 22 % of patients with invasive AC, but not in precursor lesions. CAF+ correlated with tumor stage (p = 0.004), lymphovascular tumor invasion (p = 0.018) and lymph node metastasis (p = 0.0016). Patients with CAF+ had a significant shorter disease free and overall survival (p < 0.05, Cox regression). Podoplanin expressing CAFs were only rarely observed in lymph node and distant metastases, as well as in local recurrences of ACs. Podoplanin expression in AC tumor cells was seen in only four cases. In around 20 % of patients with esophagal AC, podoplanin expressing CAFs are evident, defining a high risk subgroup. In these patients, podoplanin expressing CAFs might represent new therapeutical targets. PMID:23161183
Schoppmann, Sebastian F; Jesch, Bettina; Riegler, Martin F; Maroske, Florian; Schwameis, Katrin; Jomrich, Gerd; Birner, Peter
Perfusion of 0.1 n HC1 5 cm above the lower esophageal sphincter (LES) in cats for 30 min on 4 consecutive days produced biopsy-documented esophagitis and marked decreases in LES pressure. Using this model the effects of experimental esophagitis on the LES response to edrophonium, pentagastrin, and bethanechol were determined. The sphincter response to both edrophonium and pentagastrin after esophagitis was induced was significantly less than preperfusion responses. When the esophagitis had resolved, the pressure response to edrophonium and pentagastrin returned to preperfusion levels. In contrast, the sphincter response to bethanechol during esophagitis was not different from the preperfusion response and remained unchanged after resolution of the esophagitis. Lower esophageal smooth muscle taken from cats with active esophagitis appeared normal by both light and electron microscopy. These studies indicate that besides decreasing resting LES tone, esophageal inflammation causes functional impairment of a cholinergic mechanism regulating LES pressure. In contrast, the smooth muscle appears to be unaffected by inflammation despite the LES hypotension. PMID:1278649
Higgs, R H; Castell, D O; Eastwood, G L
The first thoracoscopic esophageal atresia with tracheoesophageal fistula (EATEF) repair was performed in March of 2000. This report evaluates the results and evolution of the technique in a single surgeons' experience after the first decade of thoracoscopic EATEF repair. From March 2000 to September 2012, 52 consecutive patients with type 3 EATEF, and an additional nine patients with pure esophageal atresia (EA) were repaired by or under the direct supervision of a single surgeon. Patient weight ranged from 1.2 to 3.8?kg (mean 2.6?kg). Twenty-two patients had significant associated congenital anomalies. The repairs were performed using three ports. The fistula was ligated using a single endoscopic clip, and the anastomosis was performed using a single layer of interrupted sutures. A transanastomotic tube and chest drain were left in all cases. Fifty-one of the 52 procedures were completed successfully thoracoscopically. Operative times ranged from 50 to 120 minutes (average 85 minutes). There were three clinical leaks, one in an EATEF and two in patients with long-gap pure EA, all resolved with conservative therapy. Oral feedings were started on day 5 in all other patients. Twelve of 61 patients required dilations (1-9), and 18 required a Nissen fundoplication for severe reflux. One patient required a thoracoscopic aortopexy for severe tracheomalacia. All patients are currently on full oral feedings. No patient has any evidence of chest wall asymmetry, winged scapula, or clinically significant scoliosis. There have been no recurrent fistulas. Thoracoscopic EA repair has proven to be an effective and safe technique. Initial experience resulted in a higher stricture rate, but this improved with experience and changes in technique. The results are superior to that of documented open series and avoid the morbidity of an open thoracotomy. PMID:23679024
Rothenberg, S S
The rupture of gastric varices results in variceal hemorrhage, which is one the most lethal complications of cirrhosis. Endoscopic therapies for varices aim to reduce variceal wall tension by obliteration of the varix. The two principal methods available for esophageal varices are endoscopic sclerotherapy (EST) and band ligation (EBL). The advantages of EST are that it is cheap and easy to use, and the injection catheter fits through the working channel of a diagnostic gastroscope. Endoscopic variceal ligation obliterates varices by causing mechanical strangulation with rubber bands. The following review aims to describe the utility of EBL and EST in different situations, such as acute bleeding, primary and secondary prophylaxis. PMID:22816012
Poza Cordon, Joaquin; Froilan Torres, Consuelo; Burgos García, Aurora; Gea Rodriguez, Francisco; Suárez de Parga, Jose Manuel
Background and Aim Negative association has been reported between presence of Helicobacter pylori and developing gastroesophageal reflux disease (GERD) and its complications. The aim of this study was to determine whether H. pylori (HP) can be protective against GERD in an African American (AA) population. Methods From 2004 to 2007, we studied 2,020 cases; esophagitis (58), gastritis (1,558), both esophagitis and gastritis (363) and a normal control group (41). We collected their pathology and endoscopy unit reports. HP status was determined based on staining of gastric biopsy. Results HP data was available for 79 % (1,611) of the cases. The frequency of HP positivity in gastritis patients was 40 % (506), in esophagitis patients 4 % and in normal controls 34 % (11), while HP was positive in 34 % of the patients with both esophagitis and gastritis. After adjusting for effects of age and sex, odds ratio of HP was 0.06 (95 % CI 0.01–0.59; P value = 0.01) for the esophagitis group versus the normal group. Conclusions Our results show H. pylori has a significant negative association with esophagitis in AAs which may point to a protective role of H. pylori in the pathogenesis of esophagitis. In addition, H. pylori may be the reason for the low GERD complications in AAs.
Entezari, Omid; Nouraie, Mehdi; Dowlati, Ehsan; Frederick, Wayne; Woods, Alfreda; Lee, Edward; Brim, Hassan; Smoot, Duane T.; Ghadyari, Firoozeh; Kamangar, Farin; Razjouyan, Hadie
Early diagnosis and accurate staging of esophageal cancer are both essential for therapeutic strategy planning. Endoscopic ultrasound, CT, and positron emission tomography have all been used in the preoperative staging of esophageal cancer separately or in various combinations. Each imaging method has its strengths and weaknesses. Depiction of the tumor's anatomic location conditions the surgical strategy. Endoscopic ultrasound and PET have important advantages but neither provides information for surgical planning. CT scans have some limitations for hollow organ assessment in the absence of lumen distension, since the organ wall may be collapsed. Therefore, optimal esophageal distension could be very useful to overcome these limitations. This potential drawback is crucial at the level of the GE junction, a typically difficult region to evaluate. In order to optimize tumor visualization in the esophageal wall and in the GE junction, we developed a technique named pneumo-64-MDCT. We achieve maximum lumen distension, which better highlights the thickened areas in relation to the normal esophageal wall. At the present time, we have performed 200 studies with this technique and it proved useful, safe and accurate to identify esophageal wall thickening and to stage esophageal cancer. The additional stomach distension led to an adequate definition of both the upper and lower borders of the lesion in tumors located in the GE junction, which in turn was helpful to design the surgical approach. PMID:21842399
Ulla, Marina; Gentile, Ernestina María José; Cavadas, Demetrio; Yeyati, Ezequiel Levy; Frank, Laura; Argerich, Javier Ithurralde; Garcia Mónaco, Ricardo
Esophageal carcinoma is one of the deadliest cancers with highly aggressive potency, ranking as the sixth most common cancer among males and ninth most common cancer among females globally. Due to metastasis and invasion of surrounding tissues in early stage, the 5-year overall survival rate (14%) of esophageal cancer remains poor, even in comparison with the dismal survival rates (4%) from the 1970s. Numerous genes and proteins with abnormal expression and function involve in the pathogenesis of esophageal cancer, but the concrete process remains unclear. Microarray technique has been applied to investigating esophageal cancer. Many gene expression studies have been undertaken to look at the specific patterns of gene transcript levels in esophageal cancer. Human tissues and cell lines were used in these geneprofiling studies and a very valuable and interesting set of data has resulted from various microarray experiments. These expression studies have provided increased understanding of the complex pathological mechanisms involved in esophageal cancer. The eventual goal of microarray is to discover new markers for therapy and to customize therapy based on an individual tumor genetic composition. This review summarized the current state of gene expression profile studies in esophageal cancer.
Guo, Wei; Jiang, Yao-Guang
...2009-10-01 false EAS public service announcements. 11.46 Section...Organization Â§ 11.46 EAS public service announcements. EAS Participants may use Public Service Announcements or obtain commercial...
...2010-10-01 false EAS public service announcements. 11.46 Section...Organization Â§ 11.46 EAS public service announcements. EAS Participants may use Public Service Announcements or obtain commercial...
Background Lymph node dissection and esophageal anastomosis, considered the more demanding steps of laparoscopic gastrectomy for gastric\\u000a adenocarcinoma, can be performed with the use of a remote-controlled robot.\\u000a \\u000a \\u000a \\u000a Methods Thirteen patients with a histologically proved gastric cancer (six stage I, six stage II, and one stage III) were enrolled\\u000a in a prospective study to assess feasibility and safety of the Da Vinci
Alberto Patriti; Graziano Ceccarelli; Raffaele Bellochi; Alberto Bartoli; Alessandro Spaziani; Lelio Di Zitti; Luciano Casciola
Esophageal involvement is an extremely rare complication of tuberculosis even in countries with high prevalence of infection. We report the case of a 57 year-old hiv-seronegative patient with simultaneous diagnoses of oral blastomycosis and laryngeal papillomatosis. Both were confirmed by anatomopathological analysis. The esophageal biopsy revealed granulomatous esophagitis with necrosis and ziehl-neelsen stain showed acid-fast alcohol resistant bacilli suggestive of tuberculosis. The patient's history included pulmonary tuberculosis twice and previous abandonment of therapy. Thus, it was necessary to use oral itraconazole combined with second-line anti-tuberculosis drugs administered through a gastrostomy tube. The clinical development was favorable. PMID:22858774
Montoya, Manuel; Chumbiraico, Robert; Ricalde, Melvin; Cazorla, Ernesto; Hernández-Córdova, Gustavo
Background: Obesity, which is one of the most serious health problems in United States, is considered a risk factor for lower esophageal and gastric cardia adenocarcinoma. However, the influence of obesity on esophageal cancer survival has not been determined. The aim of this study is to examine the impact of obesity on the long-term mortality outcomes for patients with esophageal cancer after surgery. Methods: A retrospective review was performed of 243 consecutive esophageal cancer patients undergoing surgery who did not receive neoadjuvant therapy. Patients were grouped according to pretreatment body mass index, as normal/underweight (<25 kg/m2) and overweight (?25 kg/m2). Overall and recurrence-free survivals were investigated using Kaplan-Meier method, and Cox regression model was used to determine the significant prognostic factors on univariate and multivariate analysis. Results: There were 67 patients (28%) who were classified as normal/underweight and 176 patients (72%) as overweight. In the overweight group, the numbers of patients who were male (P < .001), with adenocarcinoma (P < .001), and pathologic stage I (p=0.003) were significantly higher than in the normal/underweight group. There was no significant difference in postoperative morbidity rates between the two groups. Both local/regional and distant recurrence rates were significantly higher in the normal/underweight group (P = .027 and P = .039, respectively). The 5-year overall survival rates were 41% in the normal/underweight group, and 67% in the overweight group (P = .002). The 5-year disease free survival rates were 37% in the normal/underweight group, and 65% in the overweight group (P = .001). In univariate analysis, BMI ?25 and lower esophagus tumor were factors associated with longer survival. Factors including older age, weight loss before treatment, smoking history, squamous cell carcinoma, tumor size>3 cm, pathologic stage III, and poorly differentiated carcinoma were significantly associated with shorter patient survival. In multivariate analysis, age, pathologic stage and tumor location ultimately remained as prognostic factors. Lower esophageal tumor (P = .015; HR, 0.386; 95% CI, 0.179–0.833) was related with better survival, and older age (P = .014; HR, 1.032; 95% CI, 1.006–1.057) and stage III disease (P = .015; HR, 6.162; 95% CI, 1.744–21.766) were related with poor survival. Conclusions: Pretreatment BMI cannot be recognized as an independent predictor of long-term prognosis in esophageal cancer patients after surgery. However, high BMI tends to be associated with better prognosis. This work was supported in part by grants from UT M. D. Anderson Cancer Center, Dallas, Park, Cantu, Smith, and Myers families and by the River Creek Foundation.
Hayashi, Yuki; Correa, Arlene M.; Hofstetter, Wayne L.; Vaporciyan, Ara A.; Rice, David C.; Walsh, Garrett L.; Mehran, Reza J.; Swisher, Stephen G.; Ajani, Jaffer A.
Esophageal motor function is highly coordinated between central and enteric nervous systems and the esophageal musculature, which consists of proximal skeletal and distal smooth muscle in three functional regions, the upper and lower esophageal sphincters, and the esophageal body. While upper endoscopy is useful in evaluating for structural disorders of the esophagus, barium esophagography, radionuclide transit studies, and esophageal intraluminal impedance evaluate esophageal transit and partially assess motor function. However, esophageal manometry is the test of choice for the evaluation of esophageal motor function. In recent years, high-resolution manometry (HRM) has streamlined the process of acquisition and display of esophageal pressure data, while uncovering hitherto unrecognized esophageal physiologic mechanisms and pathophysiologic patterns. New algorithms have been devised for analysis and reporting of esophageal pressure topography from HRM. The clinical value of HRM extends to the pediatric population, and complements preoperative evaluation prior to foregut surgery. Provocative maneuvers during HRM may add to the assessment of esophageal motor function. The addition of impedance to HRM provides bolus transit data, but impact on clinical management remains unclear. Emerging techniques such as 3-D HRM and impedance planimetry show promise in the assessment of esophageal sphincter function and esophageal biomechanics. PMID:23336590
Gyawali, C P; Bredenoord, A J; Conklin, J L; Fox, M; Pandolfino, J E; Peters, J H; Roman, S; Staiano, A; Vaezi, M F
Separation of the single anterior foregut tube into the esophagus and trachea involves cell proliferation and differentiation, as well as dynamic changes in cell-cell adhesion and migration. These biological processes are regulated and coordinated at multiple levels through the interplay of the epithelium and mesenchyme. Genetic studies and in vitro modeling have shed light on relevant regulatory networks that include a number of transcription factors and signaling pathways. These signaling molecules exhibit unique expression patterns and play specific functions in their respective territories before the separation process occurs. Disruption of regulatory networks inevitably leads to defective separation and malformation of the trachea and esophagus and results in the formation of a relatively common birth defect, esophageal atresia with or without tracheoesophageal fistula (EA/TEF). Significantly, some of the signaling pathways and transcription factors involved in anterior foregut separation continue to play important roles in the morphogenesis of the individual organs. In this review, we will focus on new findings related to these different developmental processes and discuss them in the context of developmental disorders (or birth defects) commonly seen in clinics.
Jacobs, Ian J.; Ku, Wei-Yao; Que, Jianwen
Twenty-two patients with esophageal carcinoma had no local recurrence after external and intracavitary radiation treatment, but all developed ulcers in the field of intracavitary irradiation. Ten were linear ulcers that appeared 3-12 months after radiation treatment (mean, 5.3 months); the other 12 were the long circumferential type and appeared 1-8 months after irradiation (mean, 3.7 months). Esophagobronchial fistulae developed in two cases in which deep ulcer had been found between the completion of external irradiation and the beginning of intracavitary irradiation. In these cases with deep ulcer, intracavitary irradiation should not be done. For patients receiving intracavitary radiation, the total dosage should be less than 20 Gy.
Hishikawa, Y.; Tanaka, S.; Miura, T.
Esophageal manometry is a specialized procedure used to evaluate lower and upper esophageal sphincter pressure, esophageal body contraction amplitude, and peristaltic sequence. The procedure is clinically useful in evaluation of a patient with nonstructural dysphagia, unexplained or noncardiac chest pain, a compendium of symptoms suggested because of gastroesophageal reflux disease, and in the preoperative evaluation for antireflux surgery. Manometric findings in 95 normal subjects evenly distributed across age groups were reported in 1987, and are the values still used in our and most laboratories today. The subsequent review will offer our "view" on the clinical utility of esophageal manometry, on the basis of years of experience and performance techniques that have remained constant over decades. PMID:18364580
Katz, Philip O; Menin, Richard A; Gideon, R Matthew
...SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices Â§ 878.3610 Esophageal...rigid, flexible, or expandable tubular device made of a plastic, metal, or polymeric material that is...
Tracheoesophageal fistula and esophageal atresia repair is surgery to repair two birth defects in your esophagus and trachea. ... not connect with the lower esophagus and stomach. Tracheoesophageal fistula (TEF) is a connection between the upper part ...
. A case of necrotizing esophagitis discovered during upper endoscopy is described. An 88-year-old woman was admitted to our\\u000a hospital with complaints of multiple episodes of coffee ground emesis and dysphagia over 3 months. Ischemia is proposed as\\u000a the etiology of necrotizing esophagitis on the basis of the patient's significant cardiac history, her age, and low-flow state.
R. Obermeyer; K. Kasirajan; V. Erzurum; D. Chung
BACKGROUND: Esophageal cancer rate disparities are pronounced for blacks and whites. This study presents black-white esophageal cancer incidence, mortality, relative survival rates, histology and trends for two five-year time periods--1991-1995 and 1996-2000--and for the time period 1991-2000. METHODS: The study used data from the National Cancer Institute's population-based Surveillance Epidemiology End Results (SEER) program with submission dates 1991-2000. Age-adjusted incidence, mortality, relative survival rates and histology for esophageal carcinoma were calculated for nine SEER cancer registries for 1991-2000. Rates were analyzed by race and gender for changes over specified time periods. RESULTS: Esophageal cancer age-adjusted incidence of blacks was about twice that of whites (8.63 vs. 4.39/100,000, p < 0.05). Age-adjusted mortality for blacks, although showing a declining trend, was nearly twice that of whites (7.79 vs. 3.96, p < 0.05). Although survival was poor for all groups, it was significantly poorer in blacks than in whites. Squamous cell carcinoma was more commonly diagnosed in blacks and white females, whereas adenocarcinoma was more common among white males (p < 0.001). CONCLUSIONS: Racial disparities in esophageal cancer incidence, mortality, survival and histology exist. Survival rates from this disease have not significantly improved over the decade. These data support the need for advances in prevention, early detection biomarker research and research on new, more effective treatment modalities for this disease. Images Figure 1
Baquet, Claudia R.; Commiskey, Patricia; Mack, Kelly; Meltzer, Stephen; Mishra, Shiraz I.
Background: Barrett's esophagus (BE) affects up to 12 million Americans and confers an increased risk for development of esophageal adenocarcinoma (EAC). EAC is often fatal unless detected early. Given the high prevalence, high cost of surveillance and relatively low risk of most affected individuals, identification of high-risk patients for additional scrutiny, regular surveillance, or ablative therapy is crucial. The exploration of “field effect” by probing uninvolved esophageal mucosa to predict the risk of EAC has the potential as an improved surveillance and prevention strategy. In this study, we evaluate the ability of nuclear nano-architecture markers from normal squamous esophagus and gastric cardia to detect the “field effect” of esophageal dysplasia and EAC, and their response to endoscopic therapy. Methods: Patients with normal esophagus, gastroesophageal reflux, BE and EAC were eligible for enrollment. We performed endoscopic cytology brushings of the gastric cardia, ~1-2 cm below the gastroesophageal junction, and of the normal squamous esophageal mucosa at ~20 cm from the incisors and standard cytology slides were made using Thinprep method. Optical analysis was performed on the cell nuclei of cytologically normal-appearing epithelial cells. Results: The study cohort consisted of 128 patients. The nuclear nano-architecture markers detected the presence of esophageal dysplasia and EAC with statistical significance. The field effect does not exhibit a spatial dependence. These markers reverted toward normal in response to endoscopic therapy. Conclusions: Optical analysis of gastric cardia and upper squamous esophagus represents a potentially viable method to improve risk stratification and ease of surveillance of patients with Barrett's esophagus and to monitor the efficacy of ablative therapy.
Fasanella, Kenneth E.; Bista, Rajan K.; Staton, Kevin; Rizvi, Sumera; Uttam, Shikhar; Zhao, Chengquan; Sepulveda, Antonia; Brand, Randall E.; McGrath, Kevin; Liu, Yang
We present two patients who developed delayed fistulization following esophageal replacement surgery. The first is a 13-year-old child who, at the age of 3 years, underwent a trans-mediastinal colonic esophageal replacement for a refractory corrosive injury followed by a retrosternal reverse gastric tube after an early catastrophic leak. Ten years later, he presented with a history of intermittent chest pain for 6 months. He developed a tension pneumo-pericardial tamponade caused by a fistula between gastric tube and pericardium. He recovered after sternotomy. The second was born prematurely with type C esophageal atresia and other malformations. After esophageal anastomosis, he developed a refractory stricture that was resected at 10 months. Despite a fundoplication at 4 years, the recurrent esophageal stricture required resection at 14 years, accomplished by mobilizing the stomach into the chest through a left thoracoabdominal incision. The postoperative course was complicated by a gastric leak in the chest with empyema, but the patient recovered and was able to eat. Five years later, he underwent an anterior spinal fusion to correct a worsening kyphoscoliosis. Postoperatively, he developed an ARDS picture, leakage of air through the gastrostomy, and a fatal pulmonary hemorrhage secondary to a gastro-bronchial fistula. Fistulization from esophageal replacement surgery represents a rare long-term complication that pediatric surgeons need to be aware of. PMID:19349000
Abdalwahab, Ahmed; Al Namshan, Mohammed; Al Rabeeah, Abdullah; Laberge, Jean-Martin
Total laryngectomy for cancer can result in dysphagia and altered esophageal motility. Manometric changes in the upper esophageal sphincter (UES), and in proximal and distal esophageal function have been reported. However, most studies have failed to take into account radiation therapy and appropriate controls. We selected ten male patients (54.3 +/- 1.9 yr) for longitudinal manometric evaluation prior to laryngectomy then at two weeks and again six months later. No patient received preoperative radiation therapy, had a previous history of esophageal surgery, or developed a postoperative wound infection or fistula. Seven of ten patients had positive nodes and received 6,000-6,600 rads postoperative radiation therapy. Preoperatively 4 of 10 patients complained of dysphagia which did not significantly change following surgery and radiation. Two of three patients who did not complain of dysphagia preoperatively and received radiation postoperatively developed dysphagia. No patient without dysphagia preoperatively who received no radiation therapy developed symptoms. Our studies show that laryngectomy causes alterations in the UES resting and peak pressures but not in the proximal or distal esophagus, or the lower esophageal sphincter. These data also imply radiation therapy may be associated with progressive alterations in motility and symptomatology. Further study regarding the effects of radiation on esophageal motility and function are urged.
Hanks, J.B.; Fisher, S.R.; Meyers, W.C.; Christian, K.C.; Postlethwait, R.W.; Jones, R.S.
High-grade prostatic intraepithelial neoplasia (PIN) is the one well-documented precursor to adenocarcinoma of the prostate.\\u000a This review article defines both low- and high-grade PIN. Unusual variants of high-grade PIN are illustrated. Benign lesions\\u000a that may be confused with high-grade PIN, including central zone histology, clear cell cribriform hyperplasia, and basal cell\\u000a hyperplasia are described and illustrated. High-grade PIN is also
Jonathan I. Epstein
Nonbacterial thrombotic endocarditis (NBTE) is a rather frequent neoplasic complication, most often occurring in adenocarcinomas of the lung and pancreas. The most frequent clinical manifestation is one of multiple cerebral infarcts, but other ischaemic events can occur. Diagnosis is frequently missed on transthoracic ultrasound, making transoesophagic ultrasound a more reliable diagnostic tool. We present a case of NBTE associated with lung adenocarcinoma. PMID:18055331
Martín-Martorell, P; Insa-Molla, A; Chirivella-González, M I; Cervera-Miguel, J I
Background & Aims: Intraluminal pressure recording systems have not demonstrated predictable esophageal motor correlates of unexplained chest pain. This study used continuous high-frequency intraluminal ultrasonography to characterize esophageal contraction at the time of spontaneous and provoked chest pain. Methods: Intraluminal pressure, pH, and ultrasound images of the esophagus were recorded for a maximum of 24 hours in 10 subjects with
David H. Balaban; Yoshihiro Yamamoto; Jianmin Liu; Nonko Pehlivanov; Ralph Wisniewski; Dennis DeSilvey; Ravinder K. Mittal
Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection. PMID:22232645
Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin
Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.
Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa
Eosinophilic esophagitis (EoE) is a relatively new condition resulting in dysphagia or symptoms resembling gastroesophageal reflux disease, symptoms that also are common in patients with a history of esophageal atresia. We present 2 patients with persistent dysphagia after repair of esophageal atresia that was caused by EoE. Although the exact etiology and pathogenesis of EoE remain unclear, it is now generally accepted that it is the result of a T-helper cell 2-type immune response with a crucial role for the eosinophil-specific chemotaxis factor eotaxin 3 and eosinophils. Because there are genetic similarities between esophageal atresia and EoE, we speculate that patients with esophageal atresia are at increased risk for developing EoE. PMID:22703825
Gorter, Ramon R; Heij, Hugo A; van der Voorn, J Patrick; Kneepkens, C M Frank
The ingestion of food antigens plays an essential role in the development of eosinophilic esophagitis (EE) as total removal of dietary antigens by using an amino acid based oral formula improves clinical symptoms and esophageal histology in 98% of patient...
GERD, Barrett's Esophagus and the Risk for Esophageal Cancer Am I at Risk for Esophageal Cancer? There ... commonly in Caucasians as well as people with gastroesophageal reflux disease (GERD). This cancer is increasing in frequency. ...
Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.
Stoner, Gary D. [Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH 43210 (United States)], E-mail: firstname.lastname@example.org; Wang Lishu; Chen Tong [Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH 43210 (United States)
The indication of endoscopic submucosal dissection for Barrett's esophageal adenocarcinoma (BEA) is superficial BEA without lymph node metastasis. The characteristic endoscopic findings of superficial BEA are elevation, depression, and color change. Indigocarmine spreading is useful for the diagnosis of lateral extension. It is a simple and easy enhancement method. The observation of surface and vascular pattern by magnifying endoscopy with narrow-band imaging is also useful for the diagnosis of lateral extension. The incidence of gastric cancer is high in Japan. The majority of early gastric cancer is detected by conventional endoscopy without random biopsy, or target biopsydiagnosis. The background mucosa of gastric cancer has gastritis, and the carcinogenesis based on inflammation is the same as early BEA. However, random biopsy remains the universal standard for early detection of Barrett's high-grade dysplasia and superficial BEA. A surveillance system that does not use random biopsy can and should be established using high-resolution endoscopy with target biopsy. PMID:23480398
The incidence of esophageal cancer (EC), especially adenocarcinoma, has increased tremendously in Western countries and the prognosis of EC remains poor. Paeonol (Pae), a phenolic component from the root bark of Paeonia moutan, possesses antitumor effects in vitro and in vivo. The present study showed that Pae had an antiproliferative effect on the two human EC cell lines (SEG-1 and Eca-109), with different sensitivities to Pae. Acridine orange staining and flow cytometry assays showed that Pae induced apoptosis on the two cell lines. Further analyses indicated that Pae resulted in a cell cycle arrest at S-phase. Immunohistochemical staining showed the expression of Bcl-2 was decreased and that of Bax was increased in treatment groups, with the ratio of Bcl-2/Bax decreased correspondingly. The results show that Pae shows growth inhibitory and apoptosis induction property and may be a promising agent for the EC treatment. PMID:18522637
Sun, G-P; Wan, X; Xu, S-P; Wang, H; Liu, S-H; Wang, Z-G
Human epidermal growth factor receptor 2 (HER2) is overexpressed in 21% of gastric and 33% of gastroesophageal junction (GEJ) adenocarcinomas. Trastuzumab has been approved for metastatic HER2-positive gastric/GEJ cancer in combination with chemotherapy. This retrospective analysis was undertaken to better define the clinicopathologic features, treatment outcomes, and prognosis in patients with HER2-positive adenocarcinoma of the esophagus/GEJ. Pathologic specimens from 156 patients with adenocarcinoma of the esophagus/GEJ treated on clinical trials with chemoradiation and surgery were tested for HER2. Seventy-six patients also received 2 years of gefitinib. Baseline characteristics and treatment outcomes of the HER2-positive and negative patients were compared both in aggregate and separately for each of the two trials. Of 156 patients, 135 had sufficient pathologic material available for HER2 assessment. HER2 positivity was found in 23%; 28% with GEJ primaries and 15% with esophageal primaries (P= 0.10). There was no statistical difference in clinicopathologic features between HER2-positive and negative patients except HER2-negative tumors were more likely to be poorly differentiated (P < 0.001). Locoregional recurrence, distant metastatic recurrence, any recurrence, and overall survival were also statistically similar between the HER2-positive and the HER2-negative groups, in both the entire cohort and in the gefitinib-treated subset. Except for tumor differentiation, HER2-positive and negative patients with adenocarcinoma of the esophagus and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2-positive gastric cancer and the similar incidence of HER2 overexpression in esophageal/GEJ adenocarcinoma, further evaluation of HER2-directed therapy in this disease seems indicated. PMID:22676551
Phillips, B E; Tubbs, R R; Rice, T W; Rybicki, L A; Plesec, T; Rodriguez, C P; Videtic, G M; Saxton, J P; Ives, D I; Adelstein, D J
Eosinophilic and herpetic esophagitis are listed as independent causes of dysphagia, especially in young adult males. However, herpetic esophagitis rarely affects immunocompetent individuals. We report the case of a young, not immunocompromised patient, admitted because of severe dysphagia secondary to herpes simplex virus esophagitis. After complete resolution, an endoscopic and histologic reevaluation established the diagnosis of eosinophilic esophagitis. The potential association between the two conditions is discussed. PMID:23082710
Monsanto, P; Almeida, N; Cipriano, M A; Gouveia, H; Sofia, C
Esophageal stent fractures occur quite rarely. A 61-year-old male patient was previously treated for rupture of benign stenosis, occurring after dilatation, by implanting an esophageal stent. However, a year after implantation, the patient suffered from dysphagia caused by the broken esophageal stent. He was treated with the interventional radiology technique, whereby a second implantation of the esophageal stent was carried out quite successfully.
Zelenak, Kamil, E-mail: email@example.com [University Hospital, Department of Radiology (Slovakia); Mistuna, Dusan; Lucan, Jaroslav [University Hospital, Department of Surgery (Slovakia); Polacek, Hubert [University Hospital, Department of Radiology (Slovakia)
Barrett's esophagus (BE) is the main recognized risk factor for the development of esophageal adenocarcinoma (EAC). The incidence of this cancer and its associated mortality has increased in developed countries during the last few years. Detection of EAC at earlier stages could potentially improve survival dramatically in these patients, which is especially important as mortality from EAC remains high despite the available treatments. Therefore, endoscopic surveillance is an attractive option for patients with Barrett's esophagus. Consequently, periodic endoscopic surveillance is recommended by all the International Gastroenterology Societies in an attempt to detect EAC at an early and potentially curable stage. Currently, the frequency of endoscopic surveillance and its need in Barrett's esophagus with low-grade dysplasia or without dysplasia are under discussion. This review presents the available evidence in order to assist clinicians in the decision-making process. PMID:23453559
Sostres, Carlos; Lacarta, Pedro; Lanas, Angel
Some patients referred for esophagogastroduodenoscopy (EGD) to evaluate symptoms of dysphagia have normal endoscopies. How best to manage these patients is unclear. We reviewed our experience with empiric esophageal dilation in this setting. Over a five-year period, 40 consecutive patients with esophageal dysphagia and normal EGD underwent empiric esophageal dilation at the time of their endoscopy. Postdilation follow-up was available
John B. Marshall; Tabassum A. Chowdhury
Proinflammatory factors, including neutrophil-derived oxygen free radicals and inflammatory cytokines, have recently been implicated in the pathogenesis of reflux esophagitis. Rebamipide has been widely used as an anti-ulcer agent. The aim of the present study was to assess the protective effect of rebamipide against acute reflux esophagitis in rats. Esophagitis was induced in rats by ligation at the limiting ridge
Kazuhiro Katada; Norimasa Yoshida; Yutaka Isozaki; Naoya Tomatsuri; Hiroshi Ichikawa; Yuji Naito; Takeshi Okanoue; Toshikazu Yoshikawa
Esophageal atresia is a common and serious developmental anomaly, of which the causes remain largely unknown. Studies in vertebrate models indicate the importance of the sonic hedgehog pathway in esophageal atresia, but its relevance to the human condition remains to be defined. Now, three genes have been identified that cause syndromic forms of esophageal atresia when mutated. NMYC and SOX2
Han G Brunner; Hans van Bokhoven
Esophageal carcinosarcoma is a rare malignant tumor composing of both carcinomatous and sarcomatous elements. Endoscopic therapy is less invasive and may represent an alternative to esophagectomy for superficial esophageal carcinosarcoma. Here, we report a 61-year-old male who was diagnosed as esophageal carcinosarcoma and underwent endoscopic polypectomy with well tolerance and favorable prognosis. We also present a brief review of the
Feng Ji; Yue-Mei Xu; Cheng-Fu Xu
Objective: Chronic esophageal foreign bodies (CEFB) are associated with a high incidence of morbidity and mortality in adults. However, the presentation, management and outcome of chronic esophageal foreign bodies in children are not well described. Methods: We performed a retrospective chart review of children with chronic esophageal foreign bodies admitted to the Children’s Hospital Medical Center, Cincinnati, OH, between May
Robert Sean Miller; J. Paul Willging; Michael J. Rutter; Korpong Rookkapan
Background The incidence of carcinoma of the distal esophagus and GE junction is rapidly increasing. A large single-center experience was reviewed to determine the impact of lymph node positivity and ratio on survival. Methods All patients undergoing esophagogastrectomy at Thomas Jefferson University Hospital between January 1994 and December 2004 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazard models, and survival curves estimated using the Kaplan-Meier method. Results Of 173 patients with invasive cancer, 123 (71%) underwent preoperative chemoradiation therapy (CRT). The largest number of patients (45%) had adenocarcinoma of the GE junction; 29% of patients had esophageal adenocarcinoma while 14% had squamous cell cancer of the esophagus. Perioperative mortality was 5.7%. Median overall survival (OS) of the entire group was 22 months and 5-year OS was 27%. The most significant prognostic factor for overall survival was the presence of positive LN (p=0.01). Additionally, patients with zero involved LN had a 5-year survival of 34%, while patients with 1–3 positive LN and >3 positive LN had 5-year survival of 27% and 9%, respectively (p=0.01). Finally, an increasing ratio of positive to examined LN was linearly associated with a worsening 5-year survival, (p=0.153). Conclusions Increasing number of positive LN in patients with esophageal cancer and increasing ratio of metastatic to examined LN portend a poor prognosis. These factors should play an important role in determining which patients receive adjuvant therapy.
Wilson, Matthew; Rosato, Ernest L.; Chojnacki, Karen A.; Chervoneva, Inna; Kairys, John C.; Cohn, Herbert E.; Rosato, Francis E.; Berger, Adam C.
To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC. PMID:16449976
Wang, S; Zhan, M; Yin, J; Abraham, J M; Mori, Y; Sato, F; Xu, Y; Olaru, A; Berki, A T; Li, H; Schulmann, K; Kan, T; Hamilton, J P; Paun, B; Yu, M M; Jin, Z; Cheng, Y; Ito, T; Mantzur, C; Greenwald, B D; Meltzer, S J
Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced. There are no screening recommendations for patients unless they have Barrett’s esophagitis or a significant family history of this disease. Often, esophageal cancer is not diagnosed until patients present with dysphagia, odynophagia, anemia or weight loss. When symptoms occur, the stage is often stage III or greater. Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection. The treatment of patients who have locally advanced esophageal cancer is more complex and controversial. Despite multiple trials, treatment recommendations are still unclear due to conflicting data. Sadly, much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically. Additionally, studies have been underpowered or stopped early due to poor accrual. In the United States, concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient. Patients who have metastatic disease are treated palliatively. The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer, and to review the literature which guides our treatment recommendations.
Villaflor, Victoria M; Allaix, Marco E; Minsky, Bruce; Herbella, Fernando A; Patti, Marco G
Background. Soft esophageal bolus impaction is an emergency that requires skilled endoscopic removal if persistent obstructive symptoms do not resolve spontaneously after careful observation. Expedited care of these patients is crucial to avoid respiratory and mechanical complications. Other possible options for management include medical agents used to manage it prior to performing endoscopy if access to endoscopy was not available or declined by the patient. Aim. To review the available pharmacological and other nonmedicinal options and their mechanism of relief for soft esophageal impaction. Method. Pubmed, Medline and Ovid were used for search of MESH terms pertinent including "foreign body, esophageal, esophageal bolus and medical" for pharmacological and non medicinial agents used for management of esophageal soft bolus impaction as well as manual review of the cross-references. Results. Several agents were identified including Buscopan, Glucagon, nitrates, calcium channel blockers, and papaveretum. Non medicinal agents are water, effervescent agents, and papain. No evidence was found to suggest preference or effectiveness of use of a certain pharmacological agent compared to others. Buscopan, Glucagon, benzodiazepines, and nitrates were studied extensively and may be used in selected patients with caution. Use of papain is obsolete in management of soft bolus impaction. PMID:23738071
Khayyat, Yasir Mohammed
A 32-year-old woman presented with an unknown visual deficit. Fundus examination revealed a lesion compatible with a metastatic focus. Diagnostic workup revealed a lung mass and the biopsy was compatible with lung adenocarcinoma. The intraocular lesion was the only metastatic site at the time of diagnosis. She received local choroidal treatment and further systemic therapy. A pneumonectomy was performed. Five months later she progressed systemically and has since then received several lines of chemotherapy. Choroidal metastases are an infrequent site of systemic dissemination and associated with a poor prognosis, with a median survival of around 2 months if it is the first manifestation of a lung neoplasm. Here we review the literature on choroidal metastases, their treatment options and epidemiology. PMID:19828413
Martín Martorell, Paloma; Marí Cotino, José F; Insa, Amelia
Background Most inoperable patients with esophageal-advanced cancer (EGC) have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. Methods and Findings The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58±\\?8 years of age) with esophageal stenting indication were investigated. Seven patients (group 1) were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression). Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2): stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication). Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/?10 weeks and was significantly shorter in group 1 (6+/?7.6 weeks) than in group 2 (28+/?11 weeks), p<0.001). Scheduled double stenting significantly improved symptoms (95% at day 7) with a low complication rate (13%), and achieved a specific cancer treatment (84%) in most cases. Conclusion Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased airways complications related to esophageal stent. Emergency procedures were rarely efficient in our experience.
Paganin, Fabrice; Schouler, Laurent; Cuissard, Laurent; Noel, Jean Baptiste; Becquart, Jean-Philippe; Besnard, Mathieu; Verdier, Laurent; Rousseau, Denis; Arvin-Berod, Claude; Bourdin, Arnaud
Patients who have undergone repair of esophageal atresia and tracehoesophageal fistula as infants have been noted to have residual esophageal dysmotility and pulmonary dysfunction during their childhood years. However, limited information is available about the long-term follow-up of these patients. In this study we performed esophageal and pulmonary function studies on 12 adults who had required surgical repair of these
Jeffrey A. Biller; Julian L. Allen; Samuel R. Schuster; S. T. Treves; Harland S. Winter
Modern high-resolution video endoscopes allow detailed examination of the esophageal mucosa and diagnosis of early neoplastic changes in the gastrointestinal tract. Whereas Barrett's esophagus is a precancerous condition that can develop into adenocarcinoma, there is no defined precancerous lesion for squamous cell carcinoma. Various diseases are associated with the development of esophageal squamous cell carcinoma. Chromoendoscopy has become an established method in the diagnostic work-up for better visualization of early neoplasia. If Barrett's esophagus is present, acetic acid spraying or virtual chromoendoscopy can be used to accentuate the display of superficial gyriform structures in the mucosa. The gold standard for detecting squamous cell carcinoma is still the use of Lugol solution. When early neoplasia is suspected, diagnostic endoscopic resection should be performed. This allows precise histological assessment of the tumor. Early diagnosis of neoplastic changes in the esophagus provides patients not only with the option of curative therapy but also with a good quality of life through preservation of the esophagus. PMID:23657618
Behrens, A; May, A; Manner, H; Pohl, J; Ell, C
With the goal to assess the efficacy of a simple set of endoscopic ligation of esophageal varices, we conducted a prospective study in the public Goyeneche Hospital, Arequipa, Per . Ten patients between 17 and 68 years old (mean 48 years)diagnosed with digestive hemorrhage due to grade III-IV esophageal varices caused by hepatic cirrhosis were subject to endoscopic ligation. We succesfully used this simple device without overtube, in a total of 34 sessions, with 3 to 6 bands (mean 4) per session in only one introduction of endoscopy without active vericeal hemorrhage. Endoscopic treatment was repeated at 1-to-2 week intervals until variceal eradication was achieved. Only one complication (p<0.001) in the third session due to esophageal distal estenosis that was resolved with dilatation. This procedure could be useful as practical alternative of easy access and lower cost as a therapeutic option to sclerotheraphy and less complications. PMID:12138386
Five patients with early esophageal carcinoma were treated by 6-12 Gy of intracavitary irradiation following 50-60 Gy of external irradiation as a boost therapy. Surgery was not performed in these cases. None of the patients had local recurrence after radiation therapy, as demonstrated by esophagography and endoscopy. Three patients have been alive for 1-3 years 10 months. Esophageal ulceration induced by intracavitary irradiation has occurred in three of the five patients; however, intracavitary irradiation is still a beneficial treatment because of its efficacy in controlling local lesions and because radiation ulceration can eventually be cured. Intracavitary irradiation is recommended to follow external irradiation as a boost therapy for the treatment of early esophageal carcinoma.
Hishikawa, Y.; Tanaka, S.; Miura, T.
MicroRNAs (miRs) have recently emerged as a novel class of gene expression regulators. The number of studies documenting an altered miR expression pattern in cancer continues to expand rapidly. Critical information is continuously gained regarding how aberrantly expressed miRs contribute to carcinogenesis. Current studies provide evidence that analyses of miR expression patterns have potential clinical applications toward developing tumor biomarkers to identify the presence and dissemination of esophageal cancer, as well as to assess tumor chemo- or radiosensitivity. The incidence of esophageal cancer is on the rise, and this disease continues to portend a poor prognosis. The current review addresses ways in which altered miR expression contributes to esophageal carcinogenesis, along with how recent discoveries may be applied clinically.
David, Stefan; Meltzer, Stephen J.
Aims: To analyze whether outcome of neonates having esophageal atresia with or without tracheoesophageal fistula (EA±TEF) associated with anorectal malformation (ARM) can be improved by doing surgery in 2 stages. Materials and Methods: A prospective study of neonates having both EA±TEF and ARM from 2004 to 2011. The patients with favorable parameters were operated in a single stage, whereas others underwent first-stage decompression surgery for ARM. Thereafter, once septicemia was under control and ventilator care available, second-stage surgery for EA±TEF was performed. Results: Total 70 neonates (single stage = 20, 2 stages = 30, expired after colostomy = 9, only EA±TEF repair needed = 11) were enrolled. The admission rate for this association was 1 per 290. Forty-one percent (24/70) neonates had VACTERL association and 8.6% (6/70) neonates had multiple gastrointestinal atresias. Sepsis screen was positive in 71.4% (50/70). The survival was 45% (9/20) in neonates operated in a single stage and 53.3% (16/30) when operated in 2 stages (P = 0.04). Data analysis of 50 patients revealed that the survived neonates had significantly better birth weight, better gestational age, negative sepsis screen, no cardiac diseases, no pneumonia, and 2-stage surgery (P value 0.002, 0.003, 0.02, 0.02, 0.04, and 0.04, respectively). The day of presentation and abdominal distension had no significant effect (P value 0.06 and 0.06, respectively). This was further supported by stepwise logistic regression analysis. Conclusions: In a limited resources scenario, the survival rate of babies with this association can be improved by treating ARM first and then for EA±TEF in second stage, once mechanical ventilator care became available and sepsis was under control.
Singh, Sunita; Wakhlu, Ashish; Pandey, Anand; Singh, Anita; Kureel, Shiv N.; Rawat, Jiledar; Srivastava, Payal Mishra
Iron can cause oxidative stress and DNA damage, and heme iron can catalyze endogenous formation of N-nitroso compounds, which are potent carcinogens. Dietary iron promotes esophageal cancer incidence in animal studies and has been identified as a growth factor for Helicobacter pylori, an established risk factor for stomach cancer. We conducted a population-based case-control study of adenocarcinoma of the esophagus (n=124) and stomach (n=154) and 449 controls in Nebraska. Heme iron and total iron intake were estimated from a food frequency questionnaire and databases of heme and total iron. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for known risk factors. Esophageal cancer was positively associated with higher intakes of heme iron (ORQ4 vs. Q1=3.04, 95% CI: 1.20-7.72; P trend=0.009) and total iron from meat sources (ORQ4 vs. Q1=2.67, 95% CI: 0.99-7.16; P trend=0.050). Risk of stomach cancer was elevated among those with higher intakes of heme iron (ORQ4 vs.Q1=1.99, 95% CI: 1.00-3.95; P trend=0.17) and total iron from meat (OR=2.26, 95% CI: 1.14-4.46; P trend=0.11). Iron intake from all dietary sources was not significantly associated with risk of either cancer. Our results suggest that high intakes of heme and iron from meat may be important dietary risk factors for esophageal and stomach cancer and may partly explain associations with red meat. PMID:22044848
Ward, Mary H; Cross, Amanda J; Abnet, Christian C; Sinha, Rashmi; Markin, Rodney S; Weisenburger, Dennis D
Gastric adenocarcinoma is the second leading cause of cancer-related mortality worldwide. Infection with Helicobacter pylori is the strongest recognized risk factor for gastric adenocarcinoma. This bacterial species colonizes the stomach of more than half of the world’s population; however, only a very small proportion of infected subjects develop adenocarcinoma. H. pylori causes a chronic gastritis that may last decades, and a multistep precancerous process is recognized for the most frequent histologic type of gastric adenocarcinoma: the intestinal type. The severity and long-term outcome of this infection is modulated by an increasing list of bacterial, host, and environmental factors, which interplay in a complex manner. Identification of individuals at high risk for gastric cancer that may enter a surveillance program and intervention during the precancerous process is the most suitable strategy for decreasing mortality due to this malignancy.
Correa, Pelayo; Piazuelo, M Blanca
ObjectiveGlassy cell carcinoma of the cervix is a rare variant of cervical cancer accounting for a small percentage of cell types. This study was undertaken to review our experience with glassy cell adenocarcinoma.
Michael P Hopkins; George W Morley
Modern handling of esophageal cancer patients is based on a multidisciplinary concept, but surgery remains the primary curative treatment modality. Improvements in the perioperative care have reduced the overall morbidity and mortality, but 2-7% of the patients may still die within 30 days as a direct consequence of complications related to the esophagectomy procedure. Primarily based on results from randomized studies published after 2000 this review describes some of the factors that may contribute to the development of postoperative complications following esophageal cancer surgery as well as studies intended to finding ways of reducing the complication rate. PMID:24019042
Bau Mortensen, M
This study was designed to use comparative proteomics technology to find the differentially expressed proteins between human\\u000a lung adenocarcinoma and paired normal tumor-adjacent lung tissues. The total proteins of 20 human lung adenocarcinoma tissues\\u000a and paired normal tumor-adjacent lung tissues were separated by means of immobilized pH gradient-based two-dimensional gel\\u000a electrophoresis (2-DE) and Coomassie Blue staining. The differentially expressed proteins
Gaoming Xiao; Qionghui Lu; Cui Li; Wenxiang Wang; Yuejun Chen; Zhiqiang Xiao
Macroscopic intrabiliary growth of liver metastases from colonic adenocarcinoma mimicking cholangiocarcinoma, a pattern of intrahepatic spread easily confused with primary neoplasia of the biliary tract, is extremely infrequent. Resection of liver metastases has a better prognosis than that of primary neoplasia of the biliary tract. We report a case of metastasis from adenocarcinoma of the colon that presented as a Klatskin tumor. The definitive diagnosis was established by immunostaining. PMID:17949611
Fraguela Marińa, José Antonio; Fernández Blanco, Celsa; Alonso Fernández, Leticia; Taboada Filgueira, Luis; Robles Veiga, Olga; Gómez Freijoso, Carlos
Periampullary adenocarcinomas arise within 2 cm of the major papilla in the duodenum. They arise from different tissues in\\u000a the periampullary region: the head\\/neck\\/uncinate process of the pancreas, the distal common bile duct, the duodenum, and the\\u000a ampulla of Vater. Pancreatic cancer is the most common periampullary adenocarcinoma, followed by distal bile duct cancers,\\u000a ampullary cancers, and duodenal cancers (Jemal
Kanika A. Bowen; Taylor S. Riall
Drug-induced esophageal injury is an under-recognized clinical problem, and is associated with antibiotic use in more than 50% of cases. The current report describes a teenage girl who presented with symptoms of pill-induced esophagitis following doxycycline use. Subsequent investigations identified a previously undiagnosed vascular ring. Although most patients who experience drug-induced esophageal injury have no underlying anatomical or functional disorder of the esophagus, the condition is more common in areas of esophageal narrowing. The present case illustrates the possibility of an occult esophageal obstruction representing a risk factor for pill esophagitis. The etiologies, mechanisms and management of drug-induced esophageal injury are reviewed, and aspects of vascular rings that are relevant to paediatricians are discussed.
Guttman, Orlee R; Zachos, Mary
Introduction: Even after complete tumor removal by surgery, the clinical outcomes remain poor in patients with advanced esophageal cancer, justifying the need for new treatment options. Epidermal growth factor receptor (EGFR) is a molecular target for antibody-based therapy in various cancer types, and it may play important roles in the development of esophageal cancer. Areas covered: This review evaluates the expression, function, and mechanism of EGFR in esophageal cancer and analyzes its value for the prognosis and therapy of esophageal cancer. Future developments toward the clinical applications of EGFR to cancer treatment are also envisaged. Expert opinion: EGFR may function as an ideal therapeutic target for esophageal cancer. Further investigation of epidermal growth-factor-receptor-mediated pathways will push insight into the novel strategies of target therapy for esophageal cancer. More clinical trials should be performed to promote the success of therapeutic-clinical use of EGFR and its targets in esophageal cancer. PMID:23855932
Hong, Liu; Han, Yu; Brain, Lubi
OBJECTIVE: This retrospective, nonrandomized review evaluates 125 patients with esophageal carcinoma (adenocarcinoma and squamous cell) who underwent either surgery only or preoperative chemotherapy and/or radiation therapy followed by surgery. Major end points were survival and postchemoradiation downstaging. METHODS: Forty-four patients underwent radiation therapy of 4500 cGy over 5 weeks. Fluorouracil and cisplatin were administered on the first and fifth week of radiotherapy. Ninety-eight patients underwent "potentially curative" resections-transhiatal esophagectomy (70), Lewis esophagogastrectomy (25), and left esophagogastrectomy (3). All patients with preoperative adjuvant therapy underwent endoscopy and biopsy before surgery. RESULTS: There were no differences in overall mortality (5%) or surgical complications in either group. Fourteen of 44 patients (32%) downstaged to complete pathologic response, with 5-year survival of 57%. Fifteen of 44 patients (34%) downstaged to microscopic residual tumor, with 1- and 3-year survival of 77% and 31%, respectively. Twenty-eight of 29 patients in the two downstaged groups were lymph node negative. Overall, 5-year survival in the adjuvant therapy plus surgery group versus surgery only was 36% and 11% (p = 0.04). Five-year survival in lymph node-negative adjuvant therapy and surgery patients was 49% (p = 0.005). Positive nodes in the surgery only group was 48% versus 23% in the adjuvant therapy and surgery group (p = 0.02). CONCLUSION: Although retrospective and nonrandomized, these results suggest that preoperative chemoradiation results in significant clinical and pathologic downstaging, increases survival, and may sterilize local and regional lymph nodes, accounting for both downstaging and survival statistics.
Vogel, S B; Mendenhall, W M; Sombeck, M D; Marsh, R; Woodward, E R
Background: The tight junction plays a crucial role in structural esophageal epithelial defenses that maintain esophageal epithelial integrity. We examined the roles of ZO-1 and epidermal growth factor (EGF) in esophageal epithelial defense against acid using human esophageal epithelial cells. Methods: Human esophageal epithelial cells (TE-1) were incubated with acidified medium in the presence or absence of various doses of
Masatsugu Okuyama; Yasuhiro Fujiwara; Tetsuya Tanigawa; Kenji Watanabe; Masatsugu Shiba; Kazunari Tominaga; Toshio Watanabe; Nobuhide Oshitani; Kazuhide Higuchi; Tetsuo Arakawa
BACKGROUND:Patients with achalasia, diffuse esophageal spasm (DES), and nutcracker esophagus have a thicker muscularis propria than normal subjects. The goal of our study was to determine the prevalence of increased muscle thickness in a group of unselected patients referred to the esophageal function laboratory for evaluation of the symptoms.METHODS:We studied 40 normal subjects and 94 consecutive patients. Manometry and ultrasound
Ibrahim Dogan; James L. Puckett; Bikram S. Padda; Ravinder K. Mittal
Background Esophageal intestinal metaplasia, also known as Barrett’s esophagus, is the replacement of the normal epithelium with one that resembles the intestine morphologically. Generally, this includes intestinal mucin-secreting goblet cells. Barrett’s esophagus is an important risk factor for adenocarcinoma development. In vitro models for Barrett’s esophagus have not, to date, focused on the induction of goblet cells in Barrett’s epithelium. Aims To explore the contribution of Math1/Atoh1 in the induction of Barrett’s esophagus and intestinal mucin-secreting goblet cells from normal human esophageal epithelium. Methods We explored the level and pattern of Math1/Atoh1 mRNA and protein expression in human Barrett’s esophagus. Then, using retroviral-mediated gene expression, we induced Math1 mRNA and protein expression in a human esophageal keratinocyte cell line. We evaluated the effects of this ectopic Math1 expression upon cell proliferation and gene expression patterns in cells cultured under 2-dimensional and 3-dimensional tissue engineering conditions. Results Math1/Atoh1 mRNA and protein are detected in human Barrett’s esophagus specimens, but the mRNA levels vary considerable. In the keratinocyte expression studies, we observed that Math1/Atoh1 ectopic expression significantly reduced cell proliferation and altered cell morphology. Moreover, Math1/Atoh1 expression is associated with a more intestinalized gene expression pattern that is distinct from prior published studies using other intestinal transcription factors. Most significantly we observe the induction of the Barrett’s esophagus markers Mucin-2 and Keratin-20 with Math1/Atoh1 expression. Conclusions We conclude that ectopic Math1/Atoh1 expression makes unique contributions to the intestinalization of esophageal epithelium in Barrett’s esophagus.
Kong, Jianping; Crissey, Mary Ann S.; Sepulveda, Antonia R.; Lynch, John P.
Background P53 mutations are an adverse prognostic factor in esophageal cancer. P53 and KRas mutations are involved in chemo-radioresistance. Circulating anti-p53 or anti-KRas antibodies are associated with gene mutations. We studied whether anti-p53 or anti-KRas auto-antibodies were prognostic factors for response to chemoradiotherapy (CRT) or survival in esophageal carcinoma. Methods Serum p53 and KRas antibodies (abs) were measured using an ELISA method in 97 consecutive patients treated at Saint Louis University Hospital between 1999 and 2002 with CRT for esophageal carcinoma (squamous cell carcinoma (SCCE) 57 patients, adenocarcinoma (ACE) 27 patients). Patient and tumor characteristics, response to treatment and the follow-up status of 84 patients were retrospectively collected. The association between antibodies and patient characteristics was studied. Univariate and multivariate survival analyses were conducted. Results Twenty-four patients (28%) had anti-p53 abs. Abs were found predominantly in SCCE (p = 0.003). Anti-p53 abs were associated with a shorter overall survival in the univariate analysis (HR 1.8 [1.03-2.9], p = 0.04). In the multivariate analysis, independent prognostic factors for overall and progression-free survival were an objective response to CRT, the CRT strategy (alone or combined with surgery [preoperative]) and anti-p53 abs. None of the long-term survivors had p53 abs. KRas abs were found in 19 patients (23%, no difference according to the histological type). There was no significant association between anti-KRas abs and survival neither in the univariate nor in the multivariate analysis. Neither anti-p53 nor anti-KRas abs were associated with response to CRT. Conclusions Anti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population.
Esophageal obstruction from any cause is debilitating. In patients with malignant obstruction palliation to relieve pain and dysphagia is the primary goal. Conventional endoluminal prostheses allow variable palliation. Covered expandable metallic stents with an 18-mm lumen allow improved deglutition. From December 1994 through December 1998, 59 patients underwent placement of self-expanding silicone-covered esophageal stents for esophageal obstruction. There were 36 men and 23 women ranging in age from 41 to 94. All patients underwent esophageal dilation using a flexible gastroscope and Savary bougies. After dilation placement of the stent was performed under fluoroscopic control. Follow-up was complete in all patients. Technical success was achieved in all patients. There was one postoperative death (bronchopulmonary fistula), one migration of the stent requiring removal, and one recurrent obstruction. The remaining stents were well tolerated even in the cervical region (four patients). All patients returned to a diet of solid foods. We conclude that covered self-expanding esophageal metallic stents are technically simple and safe to insert and appear to provide durable excellent palliation of esophageal obstruction due to either benign or malignant conditions. PMID:11261624
Cordero, J A; Moores, D W
Expression of cyclooxygenase-2 (COX-2) is involved in the chronic inflammation-related development of Barrett's adenocarcinoma and the use of selective COX-2 inhibitors (coxibs) might provide new chemoprevention strategy for Barrett's adenocarcinoma (BA). Despite an excellent gastrointestinal (GI) safety profile of coxibs, their use is limited because of the possible cardiovascular complications. The coupling of NSAIDs with a NO-donating moiety has led to the birth of a new class of anti-inflammatory drugs, called the COX-inhibiting nitric oxide donators (CINODs). The member of this group, NO-aspirin (NO-ASA) retains the anti-inflammatory properties of traditional aspirin (ASA), but the release of NO accounts for anti-thromboembolic effect and better GI safety profile. The role of NO-ASA in the prevention of Barrett's adenocarcinoma (BA) has not been studied so far. Therefore, the aim of the present study was: 1) to analyse the expression of COX-2 in the biopsies obtained from BE; 2) to compare the effect of NO-ASA with that of ASA on proliferation rate in Barrett''s adenocarcinoma cell line (OE-33 cells); 3) to determine the effect of both compounds on the apoptosis rate using FACS analysis and expression of 32-kDa procaspase-3 and active proapoptotic 20-kDa caspase-3 in OE-33 cell line. The expression of COX-2 was assessed in biopsies obtained from the Barrett's mucosa and normal squamous epithelial esophageal mucosa from 20 BE patients by RT-PCR and Western blot analysis, respectively. The BA cell line (OE-33) was incubated with NO-ASA or ASA (10-1000 microM). The cell proliferation and apoptosis rate was measured by BrdU and FACS-analysis, respectively. The expression of caspase-3 (active and inactive form) was analyzed by Western blot. In Barrett's mucosa a significant up-regulation of COX-2 was observed. Compared with traditional ASA, NO-ASA caused a significantly stronger induction of apoptosis (dose-dependently). Inhibition of cell proliferation in OE-33 cells observed under NO-ASA treatment was due to the apoptosis induction. The increase in apoptotic rate was accompanied by the upregulation of active 20-kDa caspase-3. At the highest concentration (1000 microM), a necrotic death of OE-33 cells was observed under NO-ASA treatment. We conclude that: NO-ASA caused induction of apoptosis in BA cell line and slight growth inhibition. These results indicate that this compound may represent a promising chemopreventive agent for Barrett's adenocarcinoma. PMID:17244951
Konturek, P C; Kania, J; Burnat, G; Hahn, E G
Spontaneous esophageal rupture is an uncommon and poorly understood condition. Recurrent rupture is extremely rare, with only one previously reported case in the literature. Here, we present a case series of two patients who had recurrent ruptures, and discuss the principles underlying the management of such cases. Q 2005 Elsevier B.V. All rights reserved.
Omar A. Khan; Clifford W. Barlow; David F. Weeden; Khalid M. Amer
Auscultation of heart sound and breathing sound in anesthesia is very important, because it can provide the information of patient's cardiorespiratory system. In operating room, anesthesiologists use esophageal stethoscope, which is a device to measure heart sound or respiratory sound by inserting a catheter into the esophagus close to heart. It is not only low cost and very simple to
Ji-Yun Shin; Young Cheol Kim; Seung Woon Lim; Eun Jong Cha; Tae Soo Lee
The diagnosed multiple cancer cases have recently been increasing in number. The frequency of synchronous esophageal and gastric carcinomas is increasing due to development of more sophisticated invasive and non-invasive diagnostic tools and an increase in the number of elderly patients. Four cases of synchronous esophageal and gastric cancers were diagnosed in 2nd Department of Radiology, Medical University of Lublin and in Radiological Department of Hospital in Krosno between the 1996 and 2002. In all cases double-contrast barium examinations of upper gastrointestinal tract were performed. In all cases the two lesions were found, separated by normal mucous membrane. In two cases the irregular tumor masses were localized in the gastric cardia. In two patients coexistent lesions form the oval filling defect, with hazy appearance in the middle of the anterior esophageal wall. In three cases the results of contrast examinations were confirmed with CT. Endoscopy with taking the specimens for histopathological examination supplemented the radiological examination. The results of histopathological examinations confirmed the diagnosis. The possibility of multiple primary cancers should be kept in mind during the preoperative examination. In case of esophageal cancer with severe stricture, when endoscope cannot be passed through the esophagus, the stomach should be carefully examined in a barium meal study. PMID:16146021
Pas?awski, Marek; Z?omaniec, Janusz; Ruci?ska, Eulalia; Ko?ty?, Witold
No Heading The esophagus as a site for drug delivery has been much overlooked in comparison to the remainder of the gastrointestinal tract. The low permeability and transient nature of the esophagus means that it is unsuitable for delivery of drugs for systemic action. However, esophageal disorders including fungal infection, cancers, motility dysfunction, and damage due to gastric reflux may
INTRODUCTION Bezoar in the esophagus is a rare condition and associated with structural or functional abnormalities of the esophagus. Endoscopy is the main tool for diagnosis and treatment for bezoar in the esophagus. PRESENTATION OF CASE Here we present a case where an endoscopic evacuation of an esophageal bezoar was unsuccessful. We treated the bezoar through a nasogastric tube using a cocktail composed of pancreatic enzymes dissolved in Coca-Cola. DISCUSSION Endoscopy is regarded as the mainstay for the diagnosis and treatment of esophageal bezoars. However, when this approach fails, other treatment options include dissolution therapy, and surgical exploration and removal of the bezoar. Surgical removal of an esophageal bezoar is associated with a high risk of morbidity and mortality. We advocate that dissolving therapy should be the first choice of treatment when endoscopic evacuation is not possible. CONCLUSION This is the first report describing a successful treatment of an esophageal bezoar with a cocktail of Coca-Cola and pancreatic enzymes. It is an effective, inexpensive, and worldwide available treatment and should be considered when endoscopic evacuation fails.
Yaqub, Sheraz; Shafique, Muhammad; Kjaestad, Erik; Thorsen, Yngve; Lie, Erik S.; Dahl, Vegard; Bakka, Njal; R?kke, Ola
The authors report a series of eight cases of isolated tracheoesophageal fistula without esophageal atresia (or an H type fistula), treated in three pediatric ENT departments. This is a rare malformation whose diagnosis requires investigation for associated anomalies. The clinical signs are mainly respiratory but also digestive and the symptomatology can be severe. The diagnosis can be made with a
Erwan Genty; Pierre Attal; Richard Nicollas; Gilles Roger; Jean-Michel Triglia; Erea-Noël Garabedian; Serge Bobin
Detection of the esophagogastric junction adenocarcinoma in symptomatic stage determine a low survival. The aim of the study was to identify the prognostic factors after eso-gastrectomy for esophagogastric junction adenocarcinoma. There was done a prospective study of a 43 patients with esophago-gastric resections and abdomino-mediastinal lymph nodes dissection between 2001 and 2006 at the General and Esophageal Surgery "St. Mary" Clinical Hospital: 25 patients with transhiatal total gastrectomy, 6 patients with total gastrectomy and distal esophagectomy by separated incisions, abdominal and thoracic, 3 patients with total gastrectomy and subtotal esophagectomy by abdomino-cervical approach, 9 patients with subtotal esophagectomy by abdomino-cervical approach with cu small gastric curvature resection, radical resections in 22 patients. The patients were followed by clinic, endoscopic, TC exam and tumoral markers. There were done complex statistic analysis using SPSS 16.0. The mean interval of the surveillance was 24 months (6 - 60 months). 1 year survival was 77,74%. Long-term survival was influenced by age (p_value = 0.0129), tumoral grading (p_value = 0.0297), the number of lymph nodes metastasis (p_value = 0.0029) and pT stage (p_value = 0.0139), and was not dependent on Siewert type, ASA class, surgical approach, resection type, the number of the dissected lymph nodes, abdominal or mediastinal. In locally advanced esophagogastric junction adenocarcinoma, the frequency of lymph nodes metastasis (81%) especially in patients with tumoral type III and unfavorable results of surgical treatment as unique therapeutically method show the necessity of a multimodal approach pre and post-operatory by using selection methods with a good prediction of neoadjuvant treatment. PMID:19274907
Bîrl?, Rodica; Iosif, Cristina; Mocanu, A; Gîndea, Cristina; Hoar?, P; Panaitescu, Eugenia; Constantinoiu, S
The high incidence of dysphagia in patients with symptomatic gastroesophageal reflux (GER) but no evidence of peptic stricture suggests esophageal motor dysfunction. Conventional methods for detecting dysfunction (radiologic and manometric examinations) often fail to detect abnormality in these patients. Radionuclide transit (RT), a new method for detecting esophageal motor dysfunction, was used to prospectively assess function in 29 patients with symptomatic GER uncomplicated by stricture before and three months after antireflux surgery (HILL). The preoperative incidence of dysphagia and esophageal dysfunction was 73% and 52%, respectively. During operation (Hill repair), intraoperative measurement of the lower esophageal sphincter pressure was performed and the LESP raised to levels between 45 and 55 mmHg. The preoperative lower esophageal sphincter pressure was raised from a mean of 8.6 mmHg, to mean of 18.5 mmHg after operation. No patient has free reflux after operation. Postoperative studies on 20 patients demonstrated persistence of all preoperative esophageal dysfunction despite loss of dysphagia. RT has demonstrated a disorder of esophageal motor function in 52% of patients with symptomatic GER that may be responsible for impaired esophageal clearance. This abnormality is not contraindication to surgery. The results indicate that construction of an effective barrier to reflex corrects symptoms of reflux, even in the presence of impaired esophageal transit. Radionuclide transit is a safe noninvasive test for assessment of esophageal function.
Russell, C.O.; Pope, C.E.; Gannan, R.M.; Allen, F.D.; Velasco, N.; Hill, L.D.
Background/Aim: Current guidelines recommend screening cirrhotic patients with an endoscopy to detect esophageal varices and to institute prophylactic measures in patients with large esophageal varices. In this study, we aimed at identifying non-endoscopic parameters that could predict the presence and grades of esophageal varices. Patients and Methods: In a prospective study, 229 newly diagnosed patients with liver cirrhosis, without a history of variceal bleeding, were included. Demographic, clinical, biochemical and ultrasonographic parameters were recorded. Esophageal varices were classified as small and large, at endoscopy. Univariate analysis and multivariate logistic regression analysis were done to identify independent predictors for the presence and grades of varices. Results: Of the 229 patients (141 males; median age 42 years; range 17-73 years) with liver cirrhosis, 97 (42.3%) had small and 81 (35.4%) had large varices. On multivariate analysis, low platelet count (Odd’s Ratio [OR], 4.3; 95% confidence interval [CI], 1.2-14.9), Child Pugh class B/C (OR, 3.3; 95% CI, 1.8-6.3), spleen diameter (OR, 4.3; 95% CI, 1.6-11.9) and portal vein diameter (OR, 2.4; 95% CI, 1.1-5.3) were independent predictors for the presence of varices. Likewise, for the presence of large esophageal varices, low platelet count (OR, 2.7; 95% CI, 1.4-5.2), Child Pugh class B/C (OR, 3.8; 95% CI, 2.3-6.5) and spleen diameter (OR, 3.1; 95% CI, 1.6-6.0) were the independent risk factors. Conclusion: The presence and higher grades of varices can be predicted by a low platelet count, Child-Pugh class B/C and spleen diameter. These may be considered as non-endoscopic predictors for the diagnosis and management of large grade varices.
Cherian, Jijo V.; Deepak, Nandan; Ponnusamy, Rajesh Prabhu; Somasundaram, Aravindh; Jayanthi, V.
Background Motilin, an endogenous gastrointestinal (GI) hormone, increases upper gastrointestinal tract motility and is associated with phase III of the gastric migrating motor complex. The motilin receptor agonist, atilmotin, at doses of 6, 30 or 60 µg intravenously (IV), increases the early phase of gastric emptying. Prior studies at higher doses of 100–450 µg IV demonstrated that some subjects developed noncardiac chest pain. Aims The aim of this study is to determine the effects of atilmotin on esophageal, lower esophageal sphincter (LES), and gastric contractility and the development of esophageal-related symptoms. Methods Ten healthy volunteers underwent esophageal manometry to study the effects of atilmotin on upper GI motility. Five subjects were studied on three separate days following administration of saline placebo and subsequent IV bolus dose of atilmotin (6, 30 or 150 µg). Another five subjects were studied at the highest dose (150 µg). Results Atilmotin at 150 µg increased proximal gastric pressure by 6.5 mmHg (P = 0.001 compared with placebo). Atilmotin increased LES pressure at all studied doses; LES pressure increased from 24 ± 2 mmHg following placebo injection to 34 ± 4 mmHg following a 30 µg dose of atilmotin (P = 0.007). In the esophagus, atilmotin increased the percentage of failed swallows at the highest dose studied. Failed swallows increased from 17 ± 7% following placebo injection to 36 ± 7% following a 150 µg dose of atilmotin (P = 0.016). Atilmotin decreased distal esophageal contractile amplitude only at the highest dose studied, from 69 ± 8 mmHg (placebo) to 50 ± 5 mmHg following 150 µg atilmotin (P = 0.018). There were no serious adverse effects or episodes of chest pain with atilmotin. Conclusions Atilmotin affects esophageal, LES, and gastric motility. LES and gastric pressures were increased, whereas there was disruption of esophageal peristalsis characterized by lower amplitude and failed contractions.
Objectives: The aims of this study were to develop a new method for analysis and presentation of esophageal distensibility data using high-resolution impedance planimetry recordings during a volume-controlled distention. Methods: Two control subjects and six patients with eosinophilic esophagitis (EoE) with stricture, narrow caliber or normal endoscopy according to EndoFLIP studies were included for analysis. Median filtering and pulse detection techniques were applied to the pressure signal and a wavelet decomposition technique was applied to the 16 channels of raw esophageal diameter data to reduce vascular artifact, respiratory effect and remove esophageal contraction interference. These data were used to generate a functional luminal imaging probe (FLIP) topography plot that describes regional variation of cross-sectional area (CSA). A previously developed computer program was used to calculate and model the CSA-pressure data to derive the slope of line fitting and distension plateau for each individual subject. The results were compared among the four endoscopic phenotypes. Results: Patients with EoE and normal endoscopy had similar esophageal distensibility parameters to those of normal controls whereas patients with EoE and stricture or narrow caliber had much lower distensibility than patients with EoE and normal endoscopy. The FLIP topography plots provided a global assessment of the esophageal distensibility along the axial plane of measurement that differentiated patients with varying degrees of endoscopic abnormality. Conclusions: New techniques can be leveraged to improve data analysis and presentation using EndoFLIP assessment of the esophageal body in EoE. These techniques may be helpful in defining clinically relevant phenotypes and guiding treatment strategies and should be helpful in structuring future outcome trials.
Kahrilas, Peter J.; Xiao, Yinglian; Nicodeme, Frederic; Gonsalves, Nirmala; Hirano, Ikuo; Pandolfino, John E.
AIM: To determine if esophageal capsule endoscopy (ECE) is an adequate diagnostic alternative to esophagogastroduodenoscopy (EGD) in pre-bariatric surgery patients. METHODS: We conducted a prospective pilot study to assess the diagnostic accuracy of ECE (PillCam ESO2, Given Imaging) vs conventional EGD in pre-bariatric surgery patients. Patients who were scheduled for bariatric surgery and referred for pre-operative EGD were prospectively enrolled. All patients underwent ECE followed by standard EGD. Two experienced gastroenterologists blinded to the patient’s history and the findings of the EGD reviewed the ECE and documented their findings. The gold standard was the findings on EGD. RESULTS: Ten patients with an average body mass index of 50 kg/m2 were enrolled and completed the study. ECE identified 11 of 14 (79%) positive esophageal/gastroesophageal junction (GEJ) findings and 14 of 17 (82%) combined esophageal and gastric findings identified on EGD. Fisher’s exact test was used to compare the findings and no significant difference was found between ECE and EGD (P = 0.64 for esophageal/GEJ and P = 0.66 for combined esophageal and gastric findings respectively). Of the positive esophageal/GEJ findings, ECE failed to identify the following: hiatal hernia in two patients, mild esophagitis in two patients, and mild Schatzki ring in two patients. ECE was able to identify the entire esophagus in 100%, gastric cardia in 0%, gastric body in 100%, gastric antrum in 70%, pylorus in 60%, and duodenum in 0%. CONCLUSION: There were no significant differences in the likelihood of identifying a positive finding using ECE compared with EGD in preoperative evaluation of bariatric patients.
Shah, Ashish; Boettcher, Erica; Fahmy, Marianne; Savides, Thomas; Horgan, Santiago; Jacobsen, Garth R; Sandler, Bryan J; Sedrak, Michael; Kalmaz, Denise
Background Eosinophilic esophagitis (EE) is an emerging worldwide disease that mimics gastroesophageal reflux disease. Objective Early studies have suggested that esophageal eosinophilia occurs in association with T helper type 2 allergic responses, yet the local and systemic expression of relevant cytokines has not been well characterized. Methods A human inflammatory cytokine and receptor PCR array containing 84 genes followed by PCR validation and multiplex arrays were used to quantify cytokine mRNA in esophageal biopsies and blood levels. Results Esophageal transcripts of numerous chemokines [e.g. CCL1, CCL23, CCL26 (eotaxin-3), CXCL1, and CXCL2], cytokines (e.g. IL13 and ABCF1), and cytokine receptors (e.g. IL5RA) were induced at least 4-fold in individuals with EE. Analysis of esophageal biopsies (n=288) revealed that eotaxin-3 mRNA level alone had 89% sensitivity for distinguishing EE from non-EE individuals. The presence of allergy was associated with significantly increased esophageal expression of IL4 and IL5 mRNA in active EE patients. We identified 8 cytokines (IL-4, IL-13, IL-5, IL-6, IL-12p70, CD40L, IL-1?, and IL-17) whose blood levels retrospectively distinguished 12 non-EE from 13 EE patients with 100% specificity and 100% sensitivity. When applied to a blinded, prospectively recruited group of 36 patients, the cytokine panel scoring system had a 79% positive predictive value, 68% negative predictive value, 61% sensitivity, and 83% specificity for identifying EE. Conclusion Evidence is presented that IL13 and IL5 associate with eosinophil and eotaxin-3 levels, indicating the key role of adaptive Th2 immunity in regulating eotaxin-3-driven esophageal eosinophilia in the absence of a consistent systemic change in cytokines.
Blanchard, Carine; Stucke, Emily M.; Rodriguez-Jimenez, Beatriz; Burwinkel, Karen; Collins, Margaret H.; Ahrens, Annette; Alexander, Eileen S.; Butz, Bridget K. Buckmeier; Jameson, Sean C.; Kaul, Ajay; Franciosi, James P.; Kushner, Jonathan P.; Putnam, Philip E.; Abonia, J. Pablo; Rothenberg, Marc E.
The development and progression of lung adenocarcinoma, one of the most common cancers, is driven by the interplay of genetic and epigenetic changes and the role of chromatin structure in malignant transformation remains poorly understood. We used systematic nucleosome distribution and chromatin accessibility microarray mapping platforms to analyze the genome-wide chromatin structure from normal tissues and from primary lung adenocarcinoma of different grades and stages. We identified chromatin-based patterns across different patients with lung adenocarcinoma of different cancer grade and stage. Low-grade cancers had nucleosome distributions very different compared with the corresponding normal tissue but had nearly identical chromatin accessibility. Conversely, nucleosome distributions of high-grade cancers showed few differences. Substantial disruptions in chromosomal accessibility were seen in a patient with a high-grade and high-stage tumor. These data imply that chromatin structure changes during the progression of lung adenocarcinoma. We have therefore developed a model in which low-grade lung adenocarcinomas are linked to changes in nucleosome distributions, whereas higher-grade tumors are linked to large-scale chromosomal changes. These results provide a foundation for the development of a comprehensive framework linking the general and locus-specific roles of chromatin structure to lung cancer progression. We propose that this strategy has the potential to identify a new class of chromatin-based diagnostic, prognostic and therapeutic markers in cancer progression.
Druliner, Brooke R.; Fincher, Justin A.; Sexton, Brittany S.; Vera, Daniel L.; Roche, Michael; Lyle, Stephen; Dennis, Jonathan H.
This paper offers an evaluation of selected Canadian environmental assessment (EA) processes to reveal the extent to which they facilitate mutual learning by EA participants. The evaluation criteria were derived from transformative learning, which presents a comprehensive theory of how adults learn. Data collection methods were document review and semistructured qualitative interviews. A primary area of strength of the EA
A. John Sinclair; Alan P Diduck
Several epidemiological studies have reported on the association between body mass index (BMI) and risk of esophageal cancer, but these were mostly in Western populations where many are overweight or obese. There is little direct evidence about the relationship in China where the mean BMI is relatively low and the disease rate is high. We examined the data from a population-based prospective study of 220,000 Chinese men aged 40-79 without a previous history of cancer (mean BMI 21.7 kg/m(2)), which included 1,082 esophageal cancer deaths during 10 years of follow-up. Adjusted hazard ratios for death from esophageal cancer by baseline BMI category were calculated using Cox proportional hazards models. Even among men with good self-assessed health and BMI >or= 18.5 kg/m(2), there was a strong inverse association between BMI and death from esophageal cancer, with each 5 kg/m(2) higher BMI associated with 25% (95%CI: 11-36%) lower esophageal cancer mortality. This inverse association persisted when analysis was restricted to men who had never smoked or when the first 5 years of follow-up were excluded. The strength of the relationship was consistent with the pooled estimate for squamous cell carcinoma of the esophagus in a meta-analysis of prospective studies (31% lower relative risk per 5 kg/m(2) higher BMI; 95% CI: 25-37%), but contrasted with that for adenocarcinoma which showed a positive association with BMI. Together, these data provide reliable evidence that in many populations low BMI is associated with an increased risk of squamous cell carcinoma of the esophagus. PMID:18059032
Smith, Margaret; Zhou, Maigeng; Whitlock, Gary; Yang, Gonghuan; Offer, Alison; Hui, Gei; Peto, Richard; Huang, Zhengjing; Chen, Zhengming
Technetium-99m albumin-sucralfate ((/sup 99m/Tc)Su) can be used to demonstrate peptic ulcer disease in man and animals. We evaluated the usefulness of (/sup 99m/Tc)Su for detecting various grades of esophagitis. (/sup 99m/Tc)Su adhered to the distal esophagus for up to 3 hr in five of six patients with esophageal ulcers but adhered to only two of nine with lesser degrees of esophagitis. No adherence was seen in five patients without esophagitis. Thus, (/sup 99m/Tc)Su may not be useful for detecting any but the most severe grade of esophagitis. Based on these results, we speculate that the previously documented beneficial effects of sucralfate on mild to moderate esophagitis may be due to other mechanisms besides adherence to the ulcerated mucosa.
Goff, J.S.; Adcock, K.A.; Schmelter, R.
In many patients with chest pain of esophageal origin, findings are normal on routine esophageal manometry and dysmotility develops only upon provocation with ergonovine maleate. Unfortunately, ergonovine may induce myocardial ischemia in patients in whom coronary artery spasm did not occur during previous provocative testing in a cardiac laboratory - limiting its clinical usefulness. Esophageal pressure has been recorded simultaneously with ergonovine infusion during angiography in ten patients without significant arterial stenoses. In two patients their usual chest pain developed associated with esophageal spasm and without changes in coronary vessels. Simultaneous performance of angiography and manometry enhanced the diagnostic yield of provocative testing by showing esophageal motility changes. This method may detect significant changes in the esophageal motility, is easy to carry out and does not interfere with angiography. It maximizes the information gained from a single provocative test and avoids the risk of ergonovine infusion outside of a cardiac laboratory.
Lieberman, D.A.; Jendrzejewski, J.W.; McAnulty, J.H.
Basal cell adenocarcinoma (BCAC) is a recently described rare salivary gland tumor. They are locally invasive and destructive tumors with rare incidence of metastasis. BCAC most commonly occur in the parotid gland followed by the submandibular and other minor salivary glands. The primary management of these tumors is surgery with or without adjuvant radiotherapy. Lacrimal gland is a very rare location of BCAC; only one case has been reported in English literature. We report a case of recurrent basal cell adenocarcinoma of lacrimal gland in a 75-year-old female. She had past history of local excision of a tumor in the lacrimal gland of same side 10 years back, details of which were not available with the patient. We discuss about the case and review the literature about treatment modality in basal cell adenocarcinoma. PMID:22132848
Muduly, Dillip K; Deo, S V S; Shukla, Nootan Kumar; Yadav, Rajni; Kallianpur, Ashwin A; Samantara, Subrat
The report gives results of an evaluation of transport properties of 1,1,1,2,3,3,-hexafluoropropane (HFC-236ea), with liquid viscosity and thermal conductivity being the two main transport properties of interest. In addition, the specific heat and density of refrigerant/lubrican...