Esophageal achalasia: a risk factor for carcinoma. A systematic review and meta-analysis

Tustumi, Francisco; Bernardo, Wanderlei M.; Rocha, Júlio Rafael Mariano da; Szachnowicz, Sérgio; Seguro, Francisco Carlos Bernal da Costa; Bianchi, E; Sallum, Rubens Antônio Aissar; Cecconello, Ivan

doi:10.1093/dote/dox072

Cited by 75 publications

(50 citation statements)

References 34 publications

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“…The main risk factors for ESCC are alcohol consumption, tobacco (mainly in association) and hot-beverage consumption [3]. It is also reported that chronic diseases, such as the chagasic megaesophagus, can be associated with ESCC development [4].…”

Section: Introductionmentioning

confidence: 99%

PIK3CA mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome

Munari

Cruvinel-Carloni

Lacerda

et al. 2018

Infect Agents Cancer

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BackgroundChronic diseases such as chagasic megaesophagus (secondary to Chagas’ disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms involved are poorly understood.ObjectiveWe analyzed hotspot PIK3CA gene mutations in a series of esophageal squamous cell carcinomas associated or not with chagasic megaesophagus, as well as, in chagasic megaesophagus biopsies. We also checked for correlations between the presence of PIK3CA mutations with patients’ clinical and pathological features.MethodsThe study included three different groups of patients: i) 23 patients with chagasic megaesophagus associated with esophageal squamous cell carcinoma (CM/ESCC); ii) 38 patients with esophageal squamous cell carcinoma not associated with chagasic megaesophagus (ESCC); and iii) 28 patients with chagasic megaesophagus without esophageal squamous cell carcinoma (CM). PIK3CA hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique.ResultsPIK3CA mutations were identified in 21.7% (5 out of 23) of CM/ESCC cases, in 10.5% (4 out of 38) of ESCC and in only 3.6% (1 case out of 28) of CM cases. In the CM/ESCC group, PIK3CA mutations were significantly associated with lower survival (mean 5 months), when compared to wild-type patients (mean 2.0 years). No other significant associations were observed between PIK3CA mutations and patients’ clinical features or TP53 mutation profile.ConclusionThis is the first report on the presence of PIK3CA mutations in esophageal cancer associated with chagasic megaesophagus. The detection of PIK3CA mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targeted-therapies for these diseases.

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Section: Introductionmentioning

confidence: 99%

PIK3CA mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome

Munari

Cruvinel-Carloni

Lacerda

et al. 2018

Infect Agents Cancer

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“…In a recent meta-analysis of 40 studies (11,978 patients), Tustumi et al 43 described an incidence of squamous cell carcinoma of 312.4 cases per 1,00,000 patient-years at risk. The prevalence of ESCC in subjects with esophageal achalasia was 26 cases in 1,000, with an increase in absolute risk of squamous cell carcinoma of 308.1 cases per 1,00,000 patients per year.…”

Section: Linksmentioning

confidence: 99%

“…Furthermore, the pooled data showed that the mean survival rate after cancer diagnosis was 12.7 months and only 4.54% of the patients survived longer than 5 years. 43 …”

Section: Linksmentioning

confidence: 99%

Achalasia and esophageal cancer: risks and links

Torres-Aguilera¹,

Troche²

2018

CEG

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Esophageal cancer affects more than 4,50,000 persons worldwide, and its incidence has increased in recent years. It is the eighth most common cancer across the globe. The main histologic types are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA), and their associated risk factors are well known. Achalasia, an idiopathic esophageal disorder that conditions aperistalsis and the absence of lower esophageal sphincter relaxation, stands out among them. The prevalence of ESCC in subjects with esophageal achalasia is 26 in every 1,000 cases, whereas the prevalence of EA is 4 in every 1,000. Patients with achalasia have a 50 times higher risk of presenting with ESCC than the general population, and the disease manifests 20–25 years after achalasia symptom onset. Multiple mechanisms are related to the development of ESCC in achalasia, and they include bacterial overgrowth, food stasis, genetic alterations, and chronic inflammation. Regarding the risk of EA in achalasia patients, most cases are associated with Barrett’s esophagus, due to uncontrolled chronic acid reflux. Given that achalasia is a well-established factor for ESCC/EA, clinicians must be aware of said associations to enable the development of programs for the prevention and opportune detection of these cancers in patients with achalasia.

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“…Streitz et al (10) reported that the incidence of squamous cell carcinoma was 88/100,000 in the patients with achalasia in their study, which represents a 14.5 times greater risk than that in the general population after adjustments for age and sex. In a recent study, Tustumi et al (11) performed a systematic review and meta-analysis that showed that achalasia cardia is associated with an increased risk of esophageal cancer, highlighting the need for strict endoscopic surveillance in patients with achalasia.…”

Section: Introductionmentioning

confidence: 99%

Aflatoxin influences achalasia symptomatology

Lin

Gao

et al. 2020

Mol Med Report

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achalasia is characterized by impaired swallowing due to lower esophageal sphincter (leS) dysfunction and an increased risk of esophageal carcinoma. Aflatoxin is a known carcinogen. esophageal retention is relieved by per oral endoscopic myotomy (PoeM), which lowers the esophageal cancer risk. The present study determined whether aflatoxin is involved in the pathogenesis of achalasia or esophageal cancer. a total of 75 patients with achalasia were prospectively enrolled from a tertiary center. Aflatoxin levels in their esophageal contents were measured using eliSa, and esophageal mucosal specimens were immunohistochemically evaluated for Ki67 and p53 expression prior to and 3 months after POEM. The effect of aflatoxin on esophageal contractility was assessed using murine specimens. Aflatoxin was detected in 67 patients before PoeM and only 2 patients after PoeM. The number of Ki67-and p53-immunopositive cells in the esophageal mucosa significantly decreased after PoeM: [Ki67: 27.8% (95% confidence interval (CI), 25.98-29.70) vs. 20.7% (95% ci, 19.78-24.03), P=0.04 and p53: 2.14% (95% ci, 1.85-2.41) vs. 1.45% (95% ci, 1.22-1.68), P=0.03]. In vitro experiments revealed that 500 ng/ml aflatoxin significantly increased the amplitude (P<0.05) and frequency (P<0.05) of spontaneous leS contractions compared with the control group. These increases were blocked by co-treatment with atropine sulfate (P<0.05), but not with a nitric oxide synthase inhibitor (P>0.05). Aflatoxin was found in most patients with achalasia and was eliminated following PoeM. reduced Ki67 and p53 expression after POEM indicated a decreased risk of carcinogenesis. Aflatoxin accumulation increased LES contractility via cholinergic signaling. Therefore, aflatoxin may maintain achalasia symptoms and increase esophageal cancer risk.

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Esophageal achalasia: a risk factor for carcinoma. A systematic review and meta-analysis

Cited by 75 publications

References 34 publications

PIK3CA mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome

PIK3CA mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome

Achalasia and esophageal cancer: risks and links

Aflatoxin influences achalasia symptomatology

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