Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer?

Gastric intestinal metaplasia (GIM), which denotes conversion of gastric mucosa into an intestinal phenotype, can occur in all regions of the stomach, including cardiac, fundic, and pyloric mucosa. Since the earliest description of GIM, its association with gastric cancer of the differentiated (intestinal) type has been a well-recognized concern. Many epidemiologic studies have confirmed GIM to be significantly associated with subsequent gastric cancer development. Helicobacter pylori, the principal etiologic factor for gastric cancer, plays the most important role in predisposing to GIM. Although the role of GIM in the stepwise progression model of gastric carcinogenesis (the so-called "Correa cascade") has come into question recently, we review the scientific evidence that strongly supports this long-standing model and propose a new progression model that builds on the Correa cascade. Eradication of H pylori is the most important method for preventing gastric cancer globally, but the effect of eradication on established GIM, is limited, if any. Endoscopic surveillance for GIM may, therefore, be necessary, especially when there is extensive corpus GIM. Recent advances in image-enhanced endoscopy with integrated artificial intelligence have facilitated the identification of GIM and neoplastic lesions, which will impact preventive strategies in the near future.

Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta-analysis.

BACKGROUND: The question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta-analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random-effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses. RESULTS: Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81-0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17-1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69-0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30-2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15-1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37-2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47-1.70), Hp eradication had no advantage compared to placebo or no treatment. CONCLUSIONS: Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.

Clinical Practice Guideline for Gastritis in Korea.

Gastritis is a disease characterized by inflammation of the gastric mucosa. It is very common and has various classification systems such as the updated Sydney system. As there is a lot of evidence that Helicobacter pylori infection is associated with the development of gastric cancer and that gastric cancer can be prevented by eradication, H. pylori gastritis has been emphasized recently. The incidence rate of gastric cancer in Korea is the highest in the world, and due to the spread of screening endoscopy, atrophic gastritis and intestinal metaplasia are commonly diagnosed in the general population. However, there have been no clinical guidelines developed in Korea for these lesions. Therefore, this clinical guideline has been developed by the Korean College of Helicobacter and Upper Gastrointestinal Research for important topics that are frequently encountered in clinical situations related to gastritis. Evidence-based guidelines were developed through systematic review and de novo processes, and eight recommendations were made for eight key questions. This guideline needs to be periodically revised according to the needs of clinical practice or as important evidence about this issue is published in the future.

Threshold evaluation for optimal number of endoscopic treatment sessions to achieve complete eradication of Barrett's metaplasia.

BACKGROUND: Endoscopic eradication therapy (EET) is the standard of care for Barrett's esophagus (BE)-associated neoplasia. Previous data suggest the mean number of EET sessions required to achieve complete eradication of intestinal metaplasia (CE-IM) is 3. This study aimed to define the threshold of EET sessions required to achieve CE-IM. METHODS: The TREAT-BE Consortium is a multicenter outcomes cohort including prospectively enrolled patients with BE undergoing EET. All patients achieving CE-IM were included. Demographic, endoscopic, and histologic data were recorded at treatment onset along with treatment details and surveillance data. Kaplan-Meier analysis was performed to define a threshold of EET sessions, with 95 %CI, required to achieve CE-IM. A secondary analysis examined predictors of incomplete response to EET using multiple logistic regression and recurrence rates. RESULTS: 623 patients (mean age 65.2 [SD 11.6], 79.6 % male, 86.5 % Caucasian) achieved CE-IM in a mean of 2.9 (SD 1.7) EET sessions (median 2) and a median total observation period of 2.7 years (interquartile range 1.4-5.0). After three sessions, 73 % of patients achieved CE-IM (95 %CI 70 %-77 %). Age (odds ratio [OR] 1.25, 95 %CI 1.05-1.50) and length of BE (OR 1.24, 95 %CI 1.17-1.31) were significant predictors of incomplete response. CONCLUSION: The current study found that a threshold of three EET sessions would achieve CE-IM in the majority of patients. Alternative therapies and further diagnostic testing should be considered for patients who do not have significant response to EET after three sessions.

Ossifying pyogenic granuloma: A rare variant usually not recognized.

Pyogenic granuloma (PG) represents a polypoid and lobular, capillary lesion, resembling granulation tissue, usually occurring on skin or mucosal surfaces. The occurrence of metaplastic ossification is extremely rare in PG. We present three cases of PG with metaplastic ossification. All three patients were men, aged 18-66 years. In all cases, the lesions occurred on the digits, particularly in or around the nail bed. Histopathologically, these superficial dermal-based tumors were characterized by classic features of PG, namely circumscribed, exophytic to polypoid proliferations of capillary-sized blood vessels in a lobular arrangement. The characteristic vascular component also was intimately associated with spicules and trabeculae of metaplastic bone formation rimmed by osteoblasts and osteoclasts. This osseous component was diffusely distributed in two cases and more localized in another. We speculate that ossification in PGs possibly represents a reactive process in response to chronic injury. We believe that ossifying PG is likely under-recognized and often mistaken for other entities also arising in the extremities and characterized by osseous metaplasia.

Metaplastic breast cancer has a poor response to neoadjuvant systemic therapy.

OBJECTIVE: Metaplastic breast cancer (MetaBC) is a rare breast cancer subtype poorly responsive to systemic therapy in the metastatic setting with high recurrence rates in the adjuvant setting. However, limited data exist regarding response to neoadjuvant chemotherapy (NAC). We performed a single institutional study to assess the clinical and pathological complete response rates (pCR) of MetaBC to NAC. METHODS: Mayo Clinic Rochester patients with MetaBC treated with NAC were identified using the institutional medical index. Patient demographics, tumor characteristics, chemotherapy treatment, clinical and pathological response, and long-term outcomes were reviewed. Pathologic response was assessed by direct pathology review (n = 14) or review of outside surgical and pathology reports (n = 4). RESULTS: Women with MetaBC (n = 18) received NAC from January 1991 to June 2014. The mean age was 50 years (range 33-79) with a mean tumor size of 5.1 cm (range 2.3-11 cm) and 6/18 had pathologically confirmed lymph nodes prior to surgery. The majority (13/18; 72%) were estrogen receptor (ER), progesterone receptor (PR) and HER-2 negative (TNBC), and 1/18 (5.5%) was HER-2 positive. Five had BRCA testing and 2/5 were BRCA-2 positive. The chemotherapy regimens included anthracycline/cyclophosphamide (AC) (n = 1), AC/taxane (n = 3), AC/taxane/platinum (n = 8), taxane/platinum-based regimens (n = 4), taxane/cyclophosphamide (n = 1) and taxane/trastuzumab (n = 1). Five of 18 (28%) progressed on initial treatment including two who developed metastatic disease during NAC. The overall pCR rate was 2/18 (11%). CONCLUSION: MetaBC is poorly responsive to NAC, with a pCR rate (11%), that is lower than expected in a predominantly TNBC cohort. MetaBC patients should be considered for clinical trials testing new NAC regimens and in the absence of clinical trial enrollment, MetaBC patients with resectable disease should proceed directly to definitive operative management.

ANTIREFLUX RESECTION OF MUCOUS MEMBRANE OF ESOPHAGOGASTRIC ANASTOMOSIS IN TREATMENT OF BARRETT'S ESOPHAGUS: INITIAL EXPERIENCE.

Antireflux resection of mucous membrane of esophagogastric anastomosis (ARMS) was performed on 6 patients with typical symptoms of gastroesophageal reflux disease (GERD). The patients had a short segment of сolumnar-celled metaplasia (1-2 cm) without radiological and endoscopic signs of hiatal hernia. All the patients received medicamentous therapy by antisecretory agents more than 3 years. The operation included the endoscopic resection of2/3 circle of mucous membrane of esophagogastric anastomosis and resection of the area of columnar-celled metaplasia. The results of treatment were assessed during 3-7 months after ARMS. There was noted an absence of clinical manifestations of GERD, regression of inflammatory signs of mucous coat of esophagus in 4 out of 6 patients. Symptoms of GERD remained in 2 patients, although the intensity of signs significantly decreased.

Systematic review comparing radiofrequency ablation and complete endoscopic resection in treating dysplastic Barrett's esophagus: a critical assessment of histologic outcomes and adverse events.

BACKGROUND: With recent advances in endoscopy, endoscopic techniques have surpassed esophagectomy in the treatment of dysplastic Barrett's esophagus (BE). OBJECTIVE: To compare the efficacy and safety of complete EMR and radiofrequency ablation (RFA) in the treatment of dysplastic BE. DESIGN: Systematic review of literature. PATIENTS: Diagnosis of BE with high-grade dysplasia or intramucosal cancer. INTERVENTION: Complete EMR or RFA. MAIN OUTCOME MEASUREMENTS: Complete eradication of dysplasia and intestinal metaplasia at the end of treatment and after >12 months' follow-up. Adverse event rates associated with treatment. RESULTS: A total of 22 studies met the inclusion criteria. Only 1 trial directly compared the 2 techniques; most studies were observational case series. Dysplasia was effectively eradicated at the end of treatment in 95% of patients after complete EMR and 92% after RFA. After a median follow-up of 23 months for complete EMR and 21 months for RFA, eradication of dysplasia was maintained in 95% of patients treated with complete EMR and 94% treated with RFA. Short-term adverse events were seen in 12% of patients treated with complete EMR but in only 2.5% of those treated with RFA. Esophageal strictures were adverse events in 38% of patients treated with complete EMR, compared with 4% of those treated with RFA. Progression to cancer appeared to be rare after treatment, although follow-up was short. LIMITATIONS: Small studies, heterogeneous in design, with variable outcome measures. Also follow-up durations were short, limiting evaluation of long-term durability of both treatments. CONCLUSION: RFA and complete EMR are equally effective in the short-term treatment of dysplastic BE, but adverse event rates are higher with complete EMR.

Spinal metaplastic meningioma with osseous differentiation in the ventral thoracic spinal canal.

Ossified meningioma is classified histologically as a phenotype of metaplastic meningioma, and it is extremely rare. There are only 12 cases involving ossified spinal meningiomas in the literature. We present the case of a 61-year-old female with a primary tumor within the ventral spinal canal at T12. Although we performed a total tumor excision using an ultrasonic bone aspirator, a temporary deterioration of motor evoked potentials (MEPs) was observed during curettage with a Kerrison rongeur. The neurologic findings worsened immediately after surgery. Histologically, the tumor was diagnosed as a metaplastic meningioma with osseous differentiation. In order to avoid spinal cord injury, great care must be taken when removing an ossified meningioma located on the ventral spinal cord.

Gastric intestinal metaplasia and gastric cancer prevention: Watchful waiting.

Gastric intestinal metaplasia (GIM), a common histologic finding, is associated with increased risk of gastric cancer, and GIM associated with Helicobacter pylori infection is classified as an environmental metaplastic atrophic gastritis. Patients may be asymptomatic or present with various dyspeptic symptoms. Autoimmune metaplastic atrophic gastritis is a less common but important cause of chronic gastritis. The Correa cascade describes the evolution of precancerous mucosal changes that lead to development of GIM, with differentiation of 2 histologic types of GIM (complete and incomplete) and the consequences of each type. The risk of progression to malignancy is higher with incomplete GIM. It is also higher for those who immigrate from regions with a high incidence of H pylori infection to areas where the incidence is low. Guidelines regarding endoscopic management of GIM vary by geographic region.

Atrial Flutter After Radiofrequency Ablation for Barrett's Esophagus: A Case Report.

BACKGROUND Barrett's esophagus (BE) is a metaplastic change in the normal esophageal squamous epithelium and is a well-recognized precursor of esophageal adenocarcinoma (EAC). Nowadays, focal radiofrequency ablation is a valid technique for BE treatment by inducing a superficial and focal thermic destruction of metaplastic tissues. According to the literature, the most frequent patient-related adverse events of this procedure are esophageal iatrogenic stenosis, mucosal laceration or perforation of the esophagus, chest pain, and odynophagia/dysphagia. Postoperative heart rhythm abnormalities have been reported very rarely. CASE REPORT A 74-year-old patient with HE was treated by radiofrequency ablation (RFA) with the Barrx™ catheter system. He had 2 symptomatic episodes of atrial flutter in the immediate postoperative period requiring an external electrical cardioversion to induce a return to sinus cardiac rhythm. After atrial flutter ablation, 2 more radiofrequency procedures were performed, without adverse events. A laparoscopic Nissen fundoplication was carried out with complete endoscopic and histologic eradication of BE after 12-month follow-up. To the best of our knowledge, this is the first reported case of atrial flutter after esophageal RFA. Different mechanisms acting on an anatomic predisposing substrate can potentially play a role in starting atrial flutter, and include inflammation, autonomic activation, and myocardial injury. CONCLUSIONS The occurrence of this new type of adverse effect could potentially modify indications and postoperative monitoring of RFA treatment for BE. Endoscopists should know the possibility of this procedural complication in high-risk patients and they should propose alternative techniques or implement close cardiac monitoring in the postoperative period.

Long-term results of ablation with antireflux surgery for Barrett's esophagus: a clinical and molecular biologic study.

BACKGROUND: The initial results from ablation therapy for metaplastic/dysplastic Barrett's esophagus (BE) are promising, but the results of extended follow-up evaluation are seldom reported. METHODS: Neodymium:yttrium-aluminum-garnet laser ablation and successful antireflux surgery for 18 patients with metaplastic BE primarily resulted in the total histologic eradication of BE in 15 patients (83%). After antireflux surgery, the healing of gastroesophageal reflux disease (GERD) was objectively verified in all the patients. At late follow-up evaluation, endoscopy, conventional histology, molecular oxidative stress analyses in comparison with normal control conditions (8-hydroxydeoxyguanosine [8-OHdG], superoxide dismutase [SOD], glutathione [GSH], myeloperoxydase [MP]), and immunohistochemistry (p53, and Cdx2, caudal-related homeobox gene 2, marking intestinal differentiation) of the neosquamous epithelium were performed. RESULTS: At the end of the follow-up period (range, 3-15 years; mean, 8 years), intestinal metaplasia without dysplasia was detected histologically in eight patients (44%). Six patients had macroscopic BE (mean length, 3.5 cm; range 1-10 cm). The neosquamous epithelium was histologically normal, with no underlying columnar tissue. The fundoplication was endoscopically normal in 14 patients (82%). The 8-OHdG level was higher in the neosquamous epithelium than in the control conditions in the distal esophagus (4.3 vs. 0.52; P = 0.0002) and the proximal esophagus (1.8 vs. 0.95; P = 0.006). Likewise, SOD activity was higher in the neosquamous epithelium (0.38 vs. 0.12; P = 0.0005), whereas MP activity and GSH levels remained normal. Three patients showed slight nuclear p53 expression (typical in normal inflammatory reactions), whereas Cdx2 positivity was confined to one case with recurrent intestinal metaplasia. CONCLUSIONS: The neosquamous mucosa, generated by the ablation of BE and the treatment of GERD with fundoplication, was stable during long-term follow-up evaluation in two-thirds of the patients with initial eradication. It had normal p53 expression and no Cdx2 protein expression. The oxidative stress of the neosquamous esophagus remained high, although the clinical significance of this is unclear.

Arachnoid ossificans containing metaplastic hematopoietic marrow resulting in diffuse thoracic intrathecal cysts and severe myelopathy.

OBJECTIVE: To present a rare case of multiple compressive thoracic intradural cysts with pathologic arachnoid ossification, review the literature and present the surgical options. Few reports have identified the existence of arachnoid calcifications and intrathecal cysts causing progressive myelopathy. The literature regarding each of these pathologies is limited to case reports. Their clinical significance is not well studied, although known to cause neurologic sequelae. METHODS: An 81-year-old female clinically presents with rapidly progressive myelopathy. Pre-operative magnetic resonance imaging identified multiple compressive thoracic intrathecal cysts. Surgical exploration and decompression of these cysts identified calcified plaques within the arachnoid. Histopathologic examination revealed fibrocalcific tissue undergoing ossification with bone marrow elements. RESULTS: Due to progressive myelopathy, the thoracic cysts were decompressed and calcified plaques were excised, once identified intra-operatively. CONCLUSIONS: On last examination, the patient's neurologic status had not improved, but had stabilized. The rate of neurologic improvement from excision and decompression is variable, but it may still be warranted in the face of progressive neurologic deficits.

Detection of intestinal metaplasia after successful eradication of Barrett's Esophagus with radiofrequency ablation.

BACKGROUND: Radiofrequency ablation (RFA) is an effective means of eradicating Barrett's esophagus (BE), both with and without associated dysplasia. Several studies have documented high initial success rates with RFA. However, there is limited data on IM detection rates after eradication. AIMS: To determine the rate of detection of intestinal metaplasia (IM) after successful eradication of Barrett's esophagus. METHODS: BE patients with and without dysplasia who had undergone RFA were retrospectively identified. Only those who had complete eradication as documented on the initial post-ablation endoscopy, and had minimum two surveillance endoscopies, were included in the analyses. Clinical, demographic, and endoscopic data were collected. Cumulative incidence of IM detection was calculated by the Kaplan-Meier method. RESULTS: Forty-seven patients underwent RFA and had complete eradication of Barrett's epithelium. The majority of patients were male (76.6%), and the mean age was 64.2 years. The cumulative incidence of newly detected IM at 1 year was 25.9% (95% CI 15.1-42.1%). Dysplasia was detected at the time of recurrence in four patients, and all cases were detected at the GE junction in the absence of visible BE. Patients with recurrent IM had longer baseline segments of BE (median, 4 cm vs. 2 cm, p = 0.03). CONCLUSIONS: The rate of detection of new IM is high in patients who have undergone successful eradication of BE by RFA. Additionally, dysplasia can recur at the GE junction in the absence of visible BE. Future studies are warranted to identify those patients at increased risk for the development of recurrent intestinal metaplasia.

Osseous metaplasia late in the course of nephrogenic systemic fibrosis.

Osseous metaplasia has recently been described in several cases of nephrogenic systemic fibrosis, sometimes in association with unusual clinical features such as painful hyperkeratotic spicules, palpable bony masses, and disease regression. Some authors have suggested that it may mainly occur late in the disease course or even be a marker for involuting nephrogenic systemic fibrosis. Here, we present a 27-year-old woman with a 7-year history of nephrogenic systemic fibrosis, who developed cutaneous osseous metaplasia.

[To the question of indications for surgical treatment of gastroesophageal reflux disease and its complications].

Creating of the universal doctrine of the treatment of gastroesophageal reflux disease is one of the main problems of theoretical and practical gastroenterology. From the standpoint of modern concepts of the pathogenesis of GERD, the variety of its clinical manifestations detail the pros and cons of its pharmacological influence and antireflux surgery. Reflected tactical approaches to address the combined complications of gastroesophageal reflux. We demonstrated the efficacy of medical and surgical treatments for disease. Based on the literature analysis were performed the indications for surgical correction of individual variants of the disease.

Effectiveness of Helicobacter pylori eradication in preventing metachronous gastric cancer and preneoplastic lesions. A systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori is a significant risk factor for gastric cancer. Recent trials show eradication decreases the incidence of gastric cancer in patients with early-stage gastric cancer. However, data on gastric cancer prevention are inconsistent for patients with precancerous lesions such as atrophic gastritis and intestinal metaplasia. AIM: The aim of the study is to assess the efficacy of H. pylori eradication in gastric cancer prevention in patients with varying risk factors for gastric cancer at baseline. METHODS: A systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Medline, and Google Scholar were searched from inception through March 2019 for randomized controlled trials (RCTs) studying H. pylori eradication on gastric cancer prevention. We estimated the odds ratio (OR) with 95% confidence interval (CI) for each outcome using a random-effects model. P values of less than 0.05 were considered significant. RESULTS: Nine RCTs with total of 6967 patient were included in the analysis. There was significant reduction in gastric cancer incidence in the H. pylori group for patients with early gastric cancer status post endoscopic mucosal resection OR, 0.47; 95% CI, 0.33-0.67; P < 0.0001; I = 0%. There was no difference in gastric cancer incidence in patients with atrophic gastritis and intestinal metaplasia at baseline for H. pylori arm OR, 0.67; 95% CI, 0.42-1.07; P = 0.09; I = 0%). Atrophic gastritis and intestinal metaplasia improved from baseline in the H. pylori arm compared to placebo OR, 2.61; 95% CI, 1.41-4.81; P = 0.002; I = 88 and OR, 2.61; 95% CI, 1.66-4.11; P ≤ 0.0001; I = 0%, respectively. CONCLUSIONS: H. pylori eradication is associated with reduced gastric cancer incidence in patients with early-stage gastric cancer and improvement in atrophic gastritis and intestinal metaplasia. There was no difference in gastric cancer incidence in patients with atrophic gastritis and intestinal metaplasia at baseline.

Rational and successful use of carboplatin and albumin-bound paclitaxel in a patient with recurrent metaplastic carcinoma who presented with multi-organ tumor emboli.

We demonstrate successful treatment of recurrent chondroid-metaplastic breast cancer. Breast cancer recurrence was diagnosed when a patient with a history of metaplastic breast cancer presented with recurrent acute strokes. A diagnosis of tumor embolism was suspected when a chest radiograph performed as part of a work-up for stroke demonstrated several lung nodules, with 1 lung nodule invading the pulmonary vein and extending into the left atrium-the source of tumor emboli. This was followed by timely surgery to remove the embolizing metastatic lesion and local radiation to prevent growth and recurrent embolization. Subsequently, the patient received carboplatin and albumin-bound paclitaxel and experienced complete remission.