Infl uence of Long-Term Use of Proton Pump Inhibitors on Esophageal and Gastrointestinal Precancerous Lesions or Carcinoma

Patients with GERD and Barrett’s oesophagus should be encouraged to continue long term use of PPI therapy as a preventive measures for oesophageal adenocarcinoma. However, the conclusions, whether long-term use of PPI may casuse FGPs and gastric carcinoma development, remain inconsistent. Now, individual reports showed that long-term treatment with PPI might cause gastric neuroendocrine tumors (g-NETs) and the development of ECL cell carcinoids.Presently enormous study’s conclusion supported that long-term use of PPI does not increase in risk of colorectal cancer. Hence, clinical physicians must weigh potential risks of long-term use of PPI against gastrointestinal precancerous lesions or carcinoma. Review Article Infl uence of Long-Term Use of Proton Pump Inhibitors on Esophageal and Gastrointestinal Precancerous Lesions or Carcinoma Baoge QU1*, Hao QU2 1Department of Gastroenterology, Taishan Hospital, Shandong Province, P. R. China 2Department of Gastroenterology, Yuhuangding Hospital, Yantai city, Shandong 271000, P. R. China Dates: Received: 24 March, 2017; Accepted: 16 May, 2017; Published: 18 May, 2017 *Corresponding author: Baoge QU, Professor, Department of Gastroenterology, Taishan Hospital, Shandong Province, No. 3 Tianwaicun Street, Taiwan City 271000, P. R. China, E-mail: https://www.peertechz.com


Introduction
Previously the substantial data on long-term treatment of humans with proton pump inhibitors (PPI) has not revealed any defi nite risks [1] and prolonged gastric acid suppression with PPI rarely produced adverse event [2]. Hence, Proton pump inhibitors have an excellent safety profi le [3], supporting the short-and long-term safety of PPI [4]. They have been become a commonly prescribed class of drugs worldwide [3,5], long-term use of PPI is becoming more prevalent [6]. However, current evidences have demonstrated that long-term use of PPI might generate certain adverse events [3]. Thus, the viewpoints of adverse events for long-term use of proton pump inhibitors in human remain inconsistent. Moreover, studies have shown that chronic acid suppression by proton pump inhibitor therapy might lead to hypergastrinemia [7][8][9] and increasing enterochromaffi n-like cell dysplasia and risk of gastric.
NET development, and progression of carcinogenesis in a certain predisposed subset of Barrett's esophagus patients [9]. However, a contradictory conclusion did not support gastrin dependence of adenocarcinoma of the stomach or the colon and considering that it might be explained by the presence of gastrin receptors of tumour cells and the role of gastrin as an autocrine growth factor in some of these tumours [10]. Additionally, a study suggestd that prolonged hypochlorhydria predisposed to gastric carcinoma by an increase in the production of carcinogenic N-nitroso compounds [11].
However, accumulated evidence [12], has shown that gastrin likely does not promote-and may even suppress-distal antral gastric cancer. Hence, these hypothesises have led to concerns about the safety of long-term PPI administration [11,13]. Particularly, whether long-term use of proton pump inhibitors in human might result in esophageal and gastrointestinal precancerous lesions or carcinoma causes the extensive concern in the clinical.
1. The associations between long-term uses of proton pump inhibitors and Barrett's esophagus, esophageal cancerGastroesophageal refl ux disease (GERD) is a risk factor for the development of Barrett's esophagus and esophageal adenocarcinoma. Current evidences have confi rmed that longterm use of PPI seems to be a safe and effi cient treatment for GERD [14,15] and Barrett's oesophagus [16]. Long-term acid suppression reduced proliferation in Barrett's esophagus samples [17] and may reduce esophageal adenocarcinoma (EAC) by a minimum of 19% [18]. Use of ongoing PPI therapy appeared benefi cial in the prevention of dysplasia and adenocarcinoma in patients with Barrett's oesophagus [19]. Although PPI treatment over 1-13 years did not shorten the Barrett's oesophagus segment but squamous islands appeared in many patients, and, the incidence of oesophageal adenocarcinoma received proton pump inhibitor-treated patients was low 20].
Hence, PPI use was associated with a decreased incidence of neoplasia in Barrett's esophagus [21], supporting a cancerprotective role for PPI in patients with Barrett's esophagus Arch Clin Gastroenterol 3(2): 027-032. DOI: http://doi.org/10.17352/2455-2283.000034 [22]. However, an opposite study result revealed that PPI did not present the cancer-protective effects [23]. We summarize the above results, reconsidering that patients with GERD and Barrett's oesophagus should be encouraged to continue long term use of PPI therapy as a preventive measures for oesophageal adenocarcinoma.  [36]. However, recent study indicated no association between PPI use and the risk of gastric cancers [8]. There are tremendous reports does not support the above viewpoints, which long-term inhibition of the gastric proton pump did not increase the risk of gastric cancer because of antioxidant depletion [37]; there are no evidence that pantoprazole as a longer acting PPI conferred an excess risk of gastric cancer, other gastrointestinal cancers or all cancers compared with other shorter-acting PPI [38]. There has even study suggested that anti-carcinogenic actions of PPI were augmented with PPI-induced hypergastrinemia [39]. But,Recently a multicenter study confi rmed that elevated lesions and cobblestone-like mucosa were characteristic endoscopic features in PPI users. And ,a gender-associated difference was noted in terms of the frequency of these lesions [40]; another study results [41], pointed to a major infl uence of reverse causation and confounding by indication on the association between PPI use and gastric cancer incidence, the fi nding of increased incidence among PPI users with most prescriptions and longest follow-up warrants further investigation.In addition, PPI intake was associated with the existence and epidemiological relevance of gastric neuroendocrine tumors (g-NETs) [42,43], illustrating a patient with a poorly differentiated neuroendocrine carcinoma with ECL cell characteristics probably induced by hypergastrinemia secondary to long-term use of PPI [42]. There were reports indicating development of ECL cell carcinoids after longterm treatment with proton pump inhibitors [43] and hypergastrinemia secondary to PPI treatment might induce enterochromaffi n-like cell carcinoids in man [44,45]. Addtionally, based on few case reports showed although PPIinduced hypergastrinaemia has the potential to stimulate hyperplasia of enterochromaffi n-like (ECL) cells,however, the role was very weak , considering Physicians have to continue PPI prescription without any fear about the occurrence of this adverse event [46]. However, Children with long-termuse of PPI did not appear to develop atrophic gastritis or carcinoid tumours [47]. In short, whether long-term use of PPI might result in gastric carcinoma development and carcinoid tumours need to be verifed by large prospective studies.

The association between long-term uses of proton pump inhibitors and colorectal cancer,
Enormous researches have indicated no association between long-term use of PPI at a regular dose and the increase in risk of colorectal cancer [8,[48][49][50][51][52]. However, only a previously study suggested that PPI use might be modestly associated with CRC risk [53,54]. According to the results of the present majority studies, the conclusion seem to support the opinions, which long-term use of PPI does not increase in risk of colorectal cancer. Further research should needed to confi rm the lock of a risk-increasing effect of long-term us of PPI.

Conclusion
Patients with GERD and Barrett's oesophagus should be encouraged to continue long term use of PPI therapy as a preventive measures for oesophageal adenocarcinoma. However.whether long-term use of PPI may casuse FGPs and gastric carcinoma development remains are inconsistent. longterm treatment with PPI might cause gastric neuroendocrine tumors (g-NETs) and the development of ECL cell carcinoids. The presently study's conclusion seem to support that longterm use of PPI does not increase in risk of colorectal cancer. Hence, Physicians must weigh potential risks of long-term use of PPI against therapeutic benefi t. The continued follow-up of patients taking PPI for extended periods will provide greater experience regarding the potential gastrointestinal adverse effects of long-term acid suppression.