Esophageal Malignancy Research Articles

Detection of Merkel Cell Polyomavirus and Human Papillomavirus in Esophageal Squamous Cell Carcinomas and Non-Cancerous Esophageal Samples in Northern Iran.

Human papillomavirus (HPV) infection is one of the hypothesized causes of esophageal squamous cell carcinoma (ESCC), but the etiological association remains uncertain. It was postulated that other infectious agents together with HPV may increase the risk of ESCC. The current investigation aimed to explore the presence of a new human tumor virus, Merkel cell polyomavirus (MCPyV), together with HPV in ESCC tumors and non-cancerous esophageal samples in northern Iran. In total, 96 esophageal samples (51 with ESCC, and 45 without esophageal malignancy) were examined. HPV DNA was detected in esophageal specimens of 16 out of the 51 ESCC cases (31.4%) and 20 out of the 45 non-cancerous samples (44.4%). Untypable HPV genotypes were recognized in high rates in cancerous (75.0%) and non-cancerous (55.0%) esophageal specimens. MCPyV DNA was detected in esophageal specimens of 23 out of the 51 ESCC cases (45.1%) and 16 out of the 45 non-cancerous samples (35.6%). The mean MCPyV DNA copy number was 1.0×10(-5)±2.4×10(-5) and 6.0×10(-6)±1.3×10(-5) per cell in ESCC cases and non-cancerous samples, respectively. There was no statistically significant difference between cancerous and non-cancerous samples regarding mean MCPyV DNA load (P=0.353). A bayesian logistic regression model adjusted to the location of esophageal specimen and MCPyV infection, revealed a significant association between HPV and odds of ESCC (OR, 2.45; 95% CI: 1.01-6.16). This study provides the evidence of the detection of the MCPyV DNA at a low viral copy number in cancerous and non- cancerous esophageal samples.

Trimodality treatment for locally advanced esophageal malignancies.

174 Background: This study sought to review a single-institution experience with the management of patients with locally advanced esophageal adenocarcinoma, focusing on outcome and patterns of failure and factors affecting failure. Methods: A retrospective review of patients with locally advanced esophageal malignancies who were treated at our institution from 2002 to 2014. All patients underwent concurrent chemoradiation and surgery. Radiotherapy was delivered using 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Locoregional failure-free survival (LRFFS), distal metastasis free survival (DMFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Different factors which can affect the failure pattern were compared. Results: A total of 46 patients were analyzed. Median age was 66 years (range, 44 to 80 years). Forty three patients (93%) were men. All patients had adenocarcinoma (46% with moderately differentiated & 54% with poorly differentiated histology) involving the distal third of the esophagus. Ninety three percent were treated with 3DCRT while 7% received IMRT with a median dose of 50.4 Gy. 72 % of the tumors were downgraded after the neoadjuvant therapy, with 43 % complete response. With a median follow-up time of 22 months (range, 1 to 116 months), locoregional failure was observed in 10 patients (21%) and distant metastasis in 18 patients (39%). Among the 32 patients who died 16 patients died of disease progression and 6 patients died of post-operative complications. BMI (Body mass index) at the time of diagnosis, time elapsed between chemoradiation and surgery, history of weight loss at presentation and insertion of the J tube before neoadjuvant therapy did not affect the outcomes as per our study. Conclusions: Thoughneoadjuvant chemoradiation followed by surgery produces good pathological response to locally advanced esophageal malignancies, those results are not extrapolated to survival rates with most of the patients dying of distant metastasis. Further multi-institutional studies are required to assess other factors which are affecting the survival of esophageal cancer patients.

Endoscopic stenting for esophageal leak after minimally invasive esophagectomy.

110 Background: Anastomotic leaks can occur after esophagectomy and optimal management after minimally invasive esophagectomy (MIE) is not well defined. We reviewed endoscopic management of leaks after MIE in patients undergoing trimodality therapy at Mayo Clinic Arizona. Methods: Records of patients undergoing MIE from November, 2006 to February, 2015 were reviewed after appropriate IRB approval. Results: 148 patients underwent MIE including 136 (91.8%) thoracic and 12 (8.1%) cervical anastomoses. Clinically significant anastomotic leaks were observed in 13 (8.8%) patients with 2 (16%) cervical and 11 (8%) thoracic anastomosis at a median of 6.1 days (0-14). 11 (11%) patients treated with neoadjuvant chemoradiotherapy experienced esophageal leak and 2 who did not receive chemoradiotherapy (4%). For treatment of anastomotic leaks, 10 patients underwent VATS with pleural space irrigation and chest tube replacement, and 11 patients underwent stent deployment at the anastomosis for repair. Stents were placed such that the fistula/leak was in the fully covered portion with the greater portion of the stent residing in the esophageal remnant. Stents were removed at a mean of 54 days (28-114). In 2 patients, overgrowth into the stent body required stent-in-stent placement (fully covered) with removal of both stents. Stents were successful at sealing all leaks. Conclusions: Leaks after MIE represent a small, but significant, morbidity in MIE. The majority can be managed by endoscopic stent placement. Stenting is an effective management tool for postoperative leaks in locally advanced esophageal malignancies.

Human papillomavirus and gastrointestinal cancer: A review.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention.

Esophageal Malignancy with an Esophagorespiratory Fistula Masquerading as Pneumonia.

Esophageal Malignancy with an Esophagorespiratory Fistula Masquerading as Pneumonia.

Oesophageal malignancy with cutaneous metastasis over lower limb: A rare presentation

Oesophageal malignancy with cutaneous metastasis over lower limb: A rare presentation

Pathologic Features of Esophageal and Gastric Malignancies.

Esophageal and gastric carcinomas affect millions of individuals worldwide, placing a considerable burden on society. Unfortunately, preventative medicine falls short as screening methods for the upper gastrointestinal tract lack the ability to detect early onset disease. The overwhelming majority of cases present after symptoms appear when individuals have advanced disease with a poor prognosis. Further complicating matters, the anatomic location of these neoplasms engenders rapid tumor progression, which repeatedly thwarts successful surgical treatment. This chapter will focus on the pathological features of malignant neoplasms of the esophagus and stomach.

Photodynamic therapy in esophageal cancer

A B S T R A C T Historically, photodynamic therapy was an additional mechanism, along with external beam irradiation or brachytherapy, Nd:YAG laser tumor ablation or esophageal stent placement and to a lesser extent, chemotherapy, used to reestablish esophageal continuity in patients with esophageal malignancy who could not undergo resective surgery by virtue of infirmity or tumor stage. However, it has been virtually abandoned for this indication by most practitioners for over a decade. More recently, it has been used in the West to eradicate high-grade dysplasia and superficial malignancies arising in Barrett’s esophagus, although its expense, limited availability, and side effect profile make widespread use unlikely, particularly given the widespread availability of other effective techniques. The latter include endoscopic submucosal resection, endoscopic submucosal dissection, radiofrequency ablation, and cryotherapy. This review highlights the historical use of photodynamic therapy in the treatment of esophageal malignancy and potential roles for its application in the future.

UPPER GASTROINTESTINAL ENDOSCOPIC BIOPSY

Background: Upper GI endoscopy is an established procedure for investigatinga wide range of upper GI conditions especially inflammatory and malignant diseases ofstomach and esophagus. A good correlation in diagnosis can be achieved by complementingendoscopic findings with histology of biopsy specimens. Aims and objectives: 1) To evaluatemorphological patterns of upper GI conditions. 2) To correlate endoscopic characterization ofupper GI lesions with histopathological assessment of biopsy specimens. Study design: Aretrospective descriptive study. Period: Four year period from January 2010 to December 2013.Setting: Department of Pathology, LUMHS and were histologically assessed. Material andmethods: A total of 433 upper GI endoscopic biopsies were received. Patient’s age, gender andpresenting complaints were noted. Results: Stomach was the most frequent site of endoscopicbiopsy (51.3%) followed by esophagus (39%) and duodenum (9.7%). Majority of patients (51%)presented with dysphagia and abdominal pain. Mean age of presentation was 40 years; agerange, 9-90 years and male: female ratio is 1:1.6. Esophageal malignancy was the commonestneoplastic lesion with squamous cell carcinoma being the dominant histological type.Interestingly, inflammatory conditions were more common in the stomach. In the duodenum,celiac disease was clinically suspected and histopathological grading confirmed the diagnosiswith majority of the cases showing grade-II pathology. Conclusion: This large retrospectiveinstitutional based study showed a good correlation between endoscopic and histologicaldiagnosis. It further shows that esophagus is the predominant site of upper GI malignancy withstrong female predominance. Further studies are needed to identify the underlying risk factors.

The Impact of Severe Anastomotic Leak on Long-term Survival and Cancer Recurrence After Surgical Resection for Esophageal Malignancy.

The aim of this study was to the determine impact of severe esophageal anastomotic leak (SEAL) upon long-term survival and locoregional cancer recurrence. The impact of SEAL upon long-term survival after esophageal resection remains inconclusive with a number of studies demonstrating conflicting results. A multicenter database for the surgical treatment of esophageal cancer collected data from 30 university hospitals (2000-2010). SEAL was defined as a Clavien-Dindo III or IV leak. Patients with SEAL were compared with those without in terms of demographics, tumor characteristics, surgical technique, morbidity, survival, and recurrence. From a database of 2944 operated on for esophageal cancer between 2000 and 2010, 209 patients who died within 90 days of surgery and 296 patients with a R1/R2 resection were excluded, leaving 2439 included in the final analysis; 208 (8.5%) developed a SEAL and significant independent association was observed with low hospital procedural volume, cervical anastomosis, tumoral stage III/IV, and pulmonary and cardiovascular complications. SEAL was associated with a significant reduction in median overall (35.8 vs 54.8 months; P = 0.002) and disease-free (34 vs 47.9 months; P = 0.005) survivals. After adjustment of confounding factors, SEAL was associated with a 28% greater likelihood of death [hazard ratio = 1.28; 95% confidence interval (CI): 1.04-1.59; P = 0.022], as well as greater overall (OR = 1.35; 95% CI: 1.15-1.73; P = 0.011), locoregional (OR = 1.56; 95% CI: 1.05-2.24; P = 0.030), and mixed (OR = 1.81; 95% CI: 1.20-2.71; P = 0.014) recurrences. This large multicenter study provides strong evidence that SEAL adversely impacts cancer prognosis. The mechanism through which SEAL increases local recurrence is an important area for future research.

Nationwide analysis of short-term surgical outcomes of minimally invasive esophagectomy for malignancy

BackgroundMinimally invasive esophagectomy (MIE) is being increasingly utilized for esophageal cancer. It is unclear if MIE if being safely performed with satisfactory outcomes across the USA. We aimed to analyze the short-term surgical outcomes of MIE as compared to open esophagectomy (OE). MethodsThe National Cancer Database (NCDB) was queried for patients who underwent MIE or OE for esophageal malignancy between 2010 and 2011. Margin positivity, lymph node retrieval, 30-day mortality, 30-day unplanned readmission rate and hospital length of stay. ResultsA total of 4047 patients were identified; 3050 (75.4%) underwent OE, and 997 (24.6%) underwent MIE. The proportion of MIE increased from 21.9% in 2010 to 27.4% in 2011 (p < 0.001). The conversion rate was 13.7%. There were no differences in-patient or tumor characteristics between the two cohorts. OE and MIE were comparable in terms of margin positive resection rate (7.4% vs. 8.1%, p = 0.48), 30-day unplanned readmission rate (7.6% vs. 7.2%, p = 0.64) and 30-day mortality rate (4.3% vs. 3.3%, p = 0.71). Compared to OE, MIE was associated with higher node retrieval (median 12 vs 14, p < 0.001), and shorter hospital stay (median 11.0 vs 10.0 days, p < 0.001). Logistic regression analysis showed that surgical approach (OE vs MIE) was not associated with 30-day mortality rate. In an ANCOVA analysis, MIE was independently associated with a shorter hospital stay compared to OE (estimated mean difference 1.57 ± 0.53 days, p = 0.003). MIE patients who underwent conversion had a longer hospital stay compared to those who did not (11.0 vs 10.0 days, p = 0.02). ConclusionMIE is being offered more frequently to patients with esophageal cancer, and maybe accompanied with better short-term outcomes including shorter hospital stay when compared to open esophagectomy.

P1-5-19 - Study of the gene expression of esophageal squamous cell carcinoma-associated novel candidate genes

Background: In Taiwan, most esophageal cancer was squamous cell carcinoma; mainly happened in men, the incidence rate increased from 5.7/105 in 1995 to 17.7/105 in 2011. The ive-year survival rate was less than 15%. It becomes crucial to identify the potential genes for the prediction of esophageal cancer malignancy. In our previous study, three Taiwanese and one Caucassian ESCC cell lines as well as three normal tissues of esophagus were analyzed by using microarray technique. We have identified the most significant 10 down-regulated (DCN = PRELP, HBB, C7, HBA1, DES, COX7A1, PLVAP, IGHG4 and MYL9) and 13 up-regulated (HMGA2, ECT2, UBAP2L, ZIC2, COPA, IMP-2, HOXC13, WARS, FJX1, HOXA10, HOXD11, ADPGK and IMP-3) novel genes. Methods: In this project, we verify those potential novel genes in the RNA levels. The 23 candidate genes selected from our previous study were then investigated their gene expression using [email protected] Gene Expression Assay. 4 cancer cell line (48T, 81T, 146T, OE21) RNA were compared with a human normal esophgeal cancer RNA mixture which contains 5 asian donor RNA (BioChain). Genes with expression fold changes between samples larger than 2 are considered as differential gene expressions. Result: We found that in our down-regulated genes, DCN, HBB, C7, HBA1, DES, COX7A1, IGHG4 show low gene expresisions in all cell lines.(fold change from -47.25 ∼ -17845.58, p < 0.05); PRELP, PLVAP, MYL9 also show low gene expresisions but no statistically differences. In up-regulated group, no significantly differences were found in CE48T cell line, but HMGA2, ECT2, ZIC2, IMP-2, HOXC13, HOXA10, IMP-3 all show high gene expresisions in other 3 cell lines (fold change from 3.26 ∼ 100.45, p < 0.05). Conclusion: Compared to the findings from cell lines, we found the high consistency in terms of RNA expressions in those candidate genes, allowing us to be more confidence that these candidate genes we selected from our study may play an important role in the occurrence of ESCC.

Esophageal Cancer in a Young Patient With Celiac Disease: A Rare Association

Introduction: Risk of malignancy including lymphoma and small intestinal cancer is increased in Celiac Disease (CD). Earlier studies from the United Kingdom have also suggested a link between celiac disease and esophageal carcinoma, although this has not been confirmed in North America. This association remains a rare occurrence and is almost never seen in younger patients. We report a case of celiac disease that developed esophageal carcinoma. Case summary: 35 years old lady developed chronic diarrhea five and a half years ago. Diarrhea was associated with abdominal pain and weight loss. She lost up to 10 kg weight. Initial laboratory investigations showed iron deficiency anemia, hypoalbuminemia, decreased vitamin D and calcium. The serology for CD was positive and she was placed on a gluten free diet to which she responded. Diarrhea and abdominal pain also improved. She remained symptoms free for almost 5 years. She then presented with new onset dysphagia initially for solids and then for liquids. Barium swallow showed a shelf like projection extending into the esophageal lumen suggestive of an esophageal web. There was narrowing of the distal esophagus but Barium flowed across this area with ease. She then underwent an upper endoscopy at which time scope could not be passed beyond the web. It was dilated using a 40 mm dilator and scope was then passed to about 25 cm from the incisors. A growth was seen protruding into the esophagus at about 25 cm that almost totally occluded the lumen. Multiple biopsies were taken. This extended to the GE junction and was seen involving the gastric fundus at the gastroesophageal junction. Multiple biopsies taken. Duodenum showed decrease number and height of the folds and the biopsy also was consistent with CD. Histopathology of esophageal growth showed squamous cell carcinoma while in stomach it showed moderate chronic non specific inflammation with focal surface ulceration. Discussion: Malignant disease is a serious concern in celiac disease. Diagnosed celiac disease has been traditionally linked with greatly increased risks of lymphoma and other malignancies. An increased risk of esophageal and pharyngeal carcinoma have been shown in some European studies. Patients of CD who are undiagnosed or do not adhere to strict gluten-free diet are prone to develop complications especially malignancy. However, these findings have not been confirmed in America. Risk of malignancy persists despite of gluten free diet.This case is an unusual case of a young patient with CD and Esophageal malignancy at a very young age. It highlights the need for aggressive follow-up along with screening of malignancies associated with CD.Figure 1Figure 2

Bronchoesophageal Fistula in a Female With History of Crohnʼs Disease and Small Cell Lung Cancer

Background: Airway-esophageal fistulas are serious complications of lung or esophageal tumors. They arise either as a result of progression of lung or esophageal malignancies or manifest as a complication of chemoradiation therapy. They can also be a rare complication of Crohn's disease of the esophagus. There is limited literature on bronchoesophageal fistulas in lung cancer patients with Crohn's disease. This is a description of a case involving a middle aged female with history of Crohn's disease diagnosed with small cell lung cancer presenting with dysphagia who was found to have a bronchoesophageal fistula. Case Description: This is a 47 year old female who was diagnosed to have stricturing and fistulizing Crohn's disease 15 years ago, treated in the past with mesalamine (Asacol), prednisone, azathioprine, and infliximab on no current maintenance medications for five years who presents to clinic in December 2014 with dysphagia, nausea and vomiting. Imaging revealed a large mass in the left lower lobe abutting the mediastinum and the carina which was confirmed to be small cell lung cancer by bronchoscopy. She completed 4 cycles of cisplatin and etoposide following which she presented to clinic in May 2015 with fever, tachycardia, and hypotension as well as nausea, vomiting, cough and dysphagia. An upper endoscopy was performed revealing a large esophageal ulcer and bronchoesophageal fistula. She subsequently underwent esophageal stenting with a covered esophageal stent and open gastrostomy tube placement. Discussion: We investigate this case of a bronchoesophageal fistula in a patient with prior history of Crohn's disease and small cell lung cancer. Airway-esophageal fistulas are a known complication of tumor growth or recurrence in lung or esophageal tumors. They can also arise secondary to chemotherapy or radiation. Rarer causes include Crohn's disease, laser therapies, biologics like Bevacizumab and pressure necrosis from esophageal stents. Mean survival is 1-6 weeks. Common causes of death are respiratory infections and malnutrition. Esophageal stenting relieved symptoms in 80% of patients, was more effective (p=0.001) and led to better survival (p=0.07) and better quality of life (p=0.01) in multivariate analyses as compared to bypass or resections. Self expanding metallic stents are preferred over silicone or plastic stents.Figure 1Figure 2Figure 3

Oesophageal injury

Oesophageal injury

The Role of Antireflux Stent for Distal Esophageal Malignancy

Introduction: Incurable distal esophageal malignancy is a challenging medical condition usually requires palliative treatment with endoscopic stenting to alleviate dysphagia and provide comfort for patients. The use of conventional self expandable metal stent is associated with increased risk for acid reflux causing esophagitis, aspiration and pneumonia. Stents with antireflux mechanism have been developed to overcome this problem. We aim to perform a systematic review and meta-analysis of randomized controlled trials (RCT) comparing antireflux stent to the conventional stent for inoperable distal esophageal malignancy. Methods: We searched Pubmed and Embase for RCTs that compared antireflux stent to conventional stent. Two reviewers selected the studies. Quality for each included study was assessed by consort system. No study was eliminated based on the quality. Heterogeneity was analyzed by Cochran's Q statistics. Mantel Haenszel odds ratio (OR) and mean differences (MD) were calculated with random effects mode. RevMan 5.2 from Cochrane was used for analysis. Results: 7 RCTs involving 282 patients (133 ARS, 149 CS) were included. Insertion success rate was similar in both groups (OR: 0.46, 95% confident interval CI: 0.04, 5.75). Both stents improved dysphagia without statistically significant difference in dysphagia score between the two methods (Mean difference MD 0.23, 95% CI: -0.06, 0.53). The incidence of post stenting reflux was not statistically significant between ARS and CS (OR: 0.28, 95% CI: 0.01, 9.79). the two stents were also similar in terms of stent migration (OR: 1.28, 95% CI: 0.53, 3.08) and mortality (OR: 1.52, 95% CI: 0.49, 4.72). Conclusion: Although antireflux stent is an effective method to relief dysphagia in distal esophageal malignancy, it has failed to show superiority over the conventional stent in preventing gastroesophageal reflux.

Laparoscopic transhiatal esophagectomy improves hospital outcomes and reduces cost: a single-institution analysis of laparoscopic-assisted and open techniques.

Several case series have demonstrated that laparoscopic transhiatal esophagectomy (LTHE) is associated with favorable perioperative outcomes compared to historical data for open transhiatal esophagectomy (OTHE). Contemporaneous evaluation of open and laparoscopic THE is rare, limiting meaningful comparison of techniques. All patients who underwent OTHE (n=32) and LTHE (n=41) during the introduction of the latter procedure at our institution (1/2012-4/2014) were identified, and patient charts were retrospectively reviewed. Indications for operation included 69 patients with esophageal malignancy (adenocarcinoma: 64; squamous cell carcinoma: 4; melanoma: 1) and 4 patients with benign disease. There were no significant differences in clinicopathologic variables between OTHE and LTHE cohorts, except for an increased rate of cardiovascular disease in the LTHE cohort (p=0.04). There was no significant difference in median operative time or operative complications, yet LTHE was associated with a lower incidence of intraoperative blood transfusion (p<0.01). There were no 30-day mortalities. LTHE was associated with a reduced time to reach 24-h tube feeding goals (p=0.02), shorter length of hospital stay (p=0.01), and 6% reduced median direct cost (p=0.04). There were no significant differences in rates of major perioperative morbidities. Patients were followed for a median of 11.0months during which there were no significant differences between cohorts in disease-free survival or overall survival. When compared to OTHE, LTHE improves surgical outcomes and decreases hospital costs; short-term oncologic outcomes are similar. LTHE is preferable to OTHE in patients requiring transhiatal esophagectomy.

Comprehensive Genomic Profiling of Advanced Esophageal Squamous Cell Carcinomas and Esophageal Adenocarcinomas Reveals Similarities and Differences.

Esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for >95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S. The patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations. Next-generation sequencing-based comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a median coverage depth of >650× for all coding exons of 315 cancer-related genes plus selected introns from 28 genes frequently rearranged in cancer. Results from a single sample were evaluated for all classes of genomic alterations (GAs) including point mutations, short insertions and deletions, gene amplifications, homozygous deletions, and fusions/rearrangements. Clinically relevant genomic alterations (CRGAs) were defined as alterations linked to approved drugs and those under evaluation in mechanism-driven clinical trials. There were no significant differences by sex for either tumor type, and the median age for all patients was 63 years. All ESCCs and EACs were at an advanced stage at the time of sequencing. All 71 ESCCs and 231 EACs featured GAs on profiling, with 522 GAs in ESCC (7.4 per sample) and 1,303 GAs in EAC (5.6 per sample). The frequency of clinically relevant GAs in ESCC was 94% (2.6 per sample) and 93% in EAC (2.7 per sample). CRGAs occurring more frequently in EAC included KRAS (23% EAC vs. 6% ESCC) and ERBB2 (23% EAC vs. 3% ESCC). ESCC samples were enriched for CRGA in PIK3CA (24% ESCC vs. 10% EAC), PTEN (11% ESCC vs. 4% EAC), and NOTCH1 (17% ESCC vs. 3% EAC). Other GAs that differed significantly between histologic tumor types included SMAD4 (14% EAC vs. 1% ESCC), RB1 (14% ESCC vs. 2% EAC), SOX2 (18% ESCC vs. 1% EAC), and NFE2L2 (24% ESCC vs. 1% EAC). ESCC and EAC share similarly high frequencies of overall and clinically relevant genomic alterations; however, the profiles of genomic alterations in the two diseases differ widely, with KRAS and ERBB2 far more frequently altered in EAC compared with ESCC and with mammalian target of rapamycin (MTOR) pathway genes (PIK3CA and PTEN) and NOTCH1 more frequently altered in ESCC compared with EAC. Comprehensive genomic profiling highlights the promise of identifying clinically relevant genomic alterations in both ESCC and EAC and suggests new avenues for molecularly directed therapies in esophageal cancer.

Systematic Review With Meta-analysis: Prompt Endoscopy As the Initial Management Strategy for Uninvestigated Dyspepsia in Asi (Aliment Pharmacol Ther 2015;41:239-252).

Dyspepsia is a common gastrointestinal (GI) symptom with 10–20% of the population in the Asia-Pacific region.1 In Western countries, 40–60% of individuals have a normal examination, whilst esophageal or gastric malignancies are detected in less than 1%.2 In Asia, the prevalence of Helicobacter pylori infection and upper GI malignancies are substantially high.3,4 However, among Asian patients with uninvestigated dyspepsia, the diagnostic value of alarm features and the appropriateness of prompt endoscopy are remained uncertainly. Chen et al5 performed a systematic review to evaluate the detection rate of organic diseases including upper GI malignancies and then to propose the proper initial diagnostic strategy in Asian dyspepsia patients. Among 2410 possible references, finally 18 papers (n = 152 314) were included in the analysis of detection of organic disease by endoscopy among dyspeptic patients. This study revealed that overall malignancy detection rate was 1.3% (95% confidence interval 0.8–2.1%) and among cancer patients, 17.8% were younger than 45 years, 5.0% at age < 40 years and 3.0% at age < 35 years. The calculated detection rate of all organic diseases was 26.4% and that of peptic ulcer disease was 11.9% and esophageal disease was 5.5%. However, alarm features were shown to yield moderate diagnostic accuracy with an area under curve of 0.74. It meant limited accuracy for predicting malignancy. Therefore, authors concluded that an age of 35 years yielded relatively better diagnostic accuracy for malignancy.

Self-Expandable Metal Stents for Persisting Esophageal Variceal Bleeding after Band Ligation or Injection-Therapy: A Retrospective Study

Background and Study AimsDespite a pronounced reduction of lethality rates due to upper gastrointestinal bleeding, esophageal variceal bleeding remains a challenge for the endoscopist and still accounts for a mortality rate of up to 40% within the first 6 weeks. A relevant proportion of patients with esophageal variceal bleeding remains refractory to standard therapy, thus making a call for additional tools to achieve hemostasis. Self-expandable metal stents (SEMS) incorporate such a tool.MethodsWe evaluated a total number of 582 patients admitted to our endoscopy unit with the diagnosis “gastrointestinal bleeding” according to our documentation software between 2011 and 2014. 82 patients suffered from esophageal variceal bleeding, out of which 11 cases were refractory to standard therapy leading to SEMS application. Patients with esophageal malignancy, fistula, or stricture and a non-esophageal variceal bleeding source were excluded from the analysis. A retrospective analysis reporting a series of clinically relevant parameters in combination with bleeding control rates and adverse events was performed.ResultsThe initial bleeding control rate after SEMS application was 100%. Despite this success, we observed a 27% mortality rate within the first 42 days. All of these patients died due to non-directly hemorrhage-associated reasons. The majority of patients exhibited an extensive demand of medical care with prolonged hospital stay. Common complications were hepatic decompensation, pulmonary infection and decline of renal function. Interestingly, we found in 7 out of 11 patients (63.6%) stent dislocation at time of control endoscopy 24 h after hemostasis or at time of stent removal. The presence of hiatal hernia did not affect obviously stent dislocation rates. Refractory patients had significantly longer hospitalization times compared to non-refractory patients.ConclusionsSelf-expandable metal stents for esophageal variceal bleeding seem to be safe and efficient after failed standard therapy. Stent migration appeared to be a common incident that did not lead to reactivation of bleeding in any of our patients. SEMS should be considered a reasonable treatment option for refractory esophageal variceal bleeding after treatment failure of ligature and sclerotherapy and non-availability of or contraindication for other measures (e.g. TIPS).