A. C. de Vries

Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED)

Atrophic gastritis, intestinal metaplasia, and epithelial dysplasia of the stomach are common and are associated with an increased risk for gastric cancer. In the absence of guidelines, there is wide disparity in the management of patients with these premalignant conditions. The European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter Study Group (EHSG), the European Society of Pathology (ESP) and the Sociedade Portuguesa de Endoscopia Digestiva (SPED) have therefore combined efforts to develop evidence-based guidelines on the management of patients with precancerous conditions and lesions of the stomach (termed MAPS). A multidisciplinary group of 63 experts from 24 countries developed these recommendations by means of repeat online voting and a meeting in June 2011 in Porto, Portugal. The recommendations emphasize the increased cancer risk in patients with gastric atrophy and metaplasia, and the need for adequate staging in the case of high grade dysplasia, and they focus on treatment and surveillance indications and methods.

The Detection, Surveillance and Treatment of Premalignant Gastric Lesions Related to Helicobacter pylori Infection

Gastric cancer is an important worldwide health problem and causes considerable morbidity and mortality. It represents the second leading cause of cancer‐related death worldwide. A cascade of recognizable precursor lesions precedes most distal gastric carcinomas. In this multistep model of gastric carcinogenesis, Helicobacter pylori causes chronic active inflammation of the gastric mucosa, which slowly progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia and dysplasia to gastric carcinoma. Detection and treatment of premalignant lesions may thus provide a basis for gastric cancer prevention. However, at present, premalignant changes of the gastric mucosa are frequently disregarded in clinical practice or result in widely varying follow‐up frequency or treatment. This review provides an overview of current knowledge on detection, surveillance and treatment of patients with premalignant gastric lesions, and identifies the uncertainties that require further research.

Helicobacter pylori eradication and gastric cancer: When is the horse out of the barn

Helicobacter pylori infection is a major risk factor for gastric cancer development. Therefore, H. pylori eradication may be an important approach in the prevention of gastric cancer. However, long-term data proving the efficacy of this approach are lacking. This report describes two patients who developed gastric cancer at, respectively, 4 and 14 years after H. pylori eradication therapy. These patients were included in a study cohort of H. pylori-infected subjects who received anti-H. pylori therapy during the early years of development of H. pylori eradication therapy and underwent strict endoscopic follow-up for several years. In both patients, gastric ulcer disease and premalignant gastric lesions, i.e., intestinal metaplasia at baseline and dysplasia during follow-up, were diagnosed before gastric cancer development. These case reports demonstrate that H. pylori eradication does not prevent gastric cancer development in all infected patients after long-term follow-up. In patients with premalignant gastric lesions, in particular in patients with a history of gastric ulcer disease, adequate endoscopic follow-up is essential for early detection of gastric neoplasia.

Follow-up of premalignant lesions in patients at risk for progression to gastric cancer

BACKGROUND AND STUDY AIMSnA recent international guideline recommends surveillance of premalignant gastric lesions for patients at risk of progression to gastric cancer. The aim of this study was to identify the role of the distribution and severity of premalignant lesions in risk categorization.nnnPATIENTS AND METHODSnPatients with a previous diagnosis of atrophic gastritis, intestinal metaplasia, or low grade dysplasia were invited for surveillance endoscopy with non-targeted biopsy sampling. Biopsy specimens were evaluated by pathologists (four general and one expert) using the Sydney and the operative link for gastric intestinal metaplasia (OLGIM) systems, and scores were compared using kappa statistics.nnnRESULTSn140 patients were included. In 37 % (95 % confidence interval [CI] 29 % - 45 %) the severity of premalignant lesions was less than at baseline, while 6 % (95 %CI 2 % - 10 %) showed progression to more severe lesions. Intestinal metaplasia in the corpus was most likely to progress to more than one location (57 %; 95 %CI 36 % - 76 %). The proportion of patients with multilocated premalignant lesions increased from 24 % at baseline to 31 % at surveillance (P = 0.014). Intestinal metaplasia was the premalignant lesion most frequently identified in subsequent endoscopies. Intestinal metaplasia regressed in 27 % compared with 44 % for atrophic gastritis and 100 % for low grade dysplasia. Interobserver agreement was excellent for intestinal metaplasia (k = 0.81), moderate for dysplasia (k = 0.42), and poor for atrophic gastritis (k < 0).nnnCONCLUSIONSnPremalignant gastric lesions found in the corpus have the highest risk of progression, especially intestinal metaplasia, which has excellent interobserver agreement. This supports the importance of intestinal metaplasia as marker for follow-up in patients with premalignant gastric lesions.

Review article: Helicobacter pylori eradication for the prevention of gastric cancer

Backgroundu2002 Gastric cancer is the fourth most common cancer and second leading cause of cancer‐related death worldwide. A clear association between Helicobacter pylori infection and gastric cancer was established years ago. H. pylori eradication may be an effective approach to decrease morbidity and mortality of gastric cancer.

Varicella zoster-associated gastric ulcers, hepatitis and pancreatitis in an immunocompromised patient

continuous abdominal pain to a general hospital. His previous medical history revealed autologous stem cell transplantation for multiple myeloma 3 months before admission. This was complicated by bronchiolitis obliterans organizing pneumonia (BOOP) for which treatment was instituted with 25mg prednisone per day. An abdominal computed tomography (CT) scan showed evidence of acute pancreatitis and despite appropriate treatment intense abdominal pain persisted. During the following days he developed a skin rash, which was interpreted as druginduced, and a generalized seizure. After 7 days hewas referred to our hospital. Physical examination revealed an ill man in great pain. On clinical examination he had a maculovesicular rash on the face, trunk, and abdomen (● Fig. 1). Laboratory investigation showed elevated serum aspartate aminotransferase of 1038 U/l (normal 0–36 U/l), alanine aminotransferase 848 U/l (normal 0–40 U/l), amylase 158 U/l (normal 0–99 U/l), C-reactive protein 57mg/l (normal 0–9mg/l), and leukocyte count 3.2 × 109/L (normal, 3.5– 10.0 × 109/L). A chest X-ray showed diffuse infiltrative pulmonary abnormalities. Upper gastrointestinal endoscopy revealed multiple well-demarcated superficial erosions with a white patchy surface in the esophagus (● Fig. 2). In the fundus, corpus, and antrum of the stomach, multiple ulcers with central necrosis were present, ranging from 5mm to 10mm in diameter (● Fig. 3). The abdominal pain, skin rash, and the multiple ulcerations in the esophagus and stomach raised clinical suspicion of varicella zoster virus (VZV) infection. Polymerase chain reaction (PCR) revealed VZV genome in serum, as well as in skin and gastric biopsies. VZV is an unsuspected cause of severe acute abdominal pain and patients may present with hepatitis, pancreatitis, and gastroesophageal mucositis. Moreover, VZV infection is the most common viral disease after bone marrow transplantation, occurring in 17–50% of patients, with a median interval of 3–6 months [1,2]. In the majority of cases, cutaneous manifestations precede those of abdominal organ dissemination, making early diagnosis more likely [2]. Timely diagnosis and prompt treatment may diminishmortality, which ranges from 9% to 55% [1– 3]. In most cases, latent VZV is reactivated from the dorsal root ganglia, which share the afferent sympathetic fibers that supply the liver, pancreas, gastrointestinal mucosa, and lungs [3]. Since posterior sensory nerve roots contain fibers from both skin and abdominal viscera, these organs are potential candidates to be affected [3]. In our patient, all of these organs were affected and after treatment with intravenous aciclovir 10mg/kg/8 h, the abdominal pain as well as the cutaneous and pulmonary abnormalities disappeared and serum amylase and transaminase levels normalized. In conclusion, the combination of multiple gastric ulcers, pancreatitis, hepatitis, and a skin rash should raise the possibility of disseminated VZV infection, especially following bone marrow transplantation.

Bovine antibody-based oral immunotherapy for reduction of intragastric Helicobacter pylori colonization: A randomized clinical trial

BACKGROUNDnAntibiotic-based regimens are frequently used for the treatment of Helicobacter pylori infection. These regimens fail to eradicate H pylori in 15% to 40% of patients, primarily due to antimicrobial resistance and insufficient patient compliance. Effective prevention and eradication of H pylori by passive immunization with orally administered bovine antibodies has been demonstrated in animal studies, and may serve as an alternative therapy in humans.nnnOBJECTIVEnTo study the efficacy and safety of orally administered bovine anti-H pylori antibodies for the reduction of intragastric bacterial load and eradication of H pylori in humans.nnnMETHODSnDairy cows were immunized against H pylori. After confirmation of the presence of anti-H pylori antibodies in the milk, the milk was subsequently processed into a whey protein concentrate (WPC). In a prospective, double-blind, placebo-controlled randomized clinical trial, H pylori-infected subjects were randomly assigned to treatment with the WPC preparation or placebo. Study medication was continued for 28 days; subjects were followed-up for 56 days.nnnRESULTSnOf the 30 subjects included, 27 completed the protocol. Of these 27 evaluable subjects, 14 were treated with WPC and 13 with placebo. There was no significant difference in urea breath test decrease between the WPC- and placebo-treated group (P=0.75). H pylori-associated gastritis and density were not significantly reduced in either group after treatment (P>0.05 for all).nnnCONCLUSIONnBovine antibody-based oral immunotherapy appears to be safe, but does not significantly reduce intragastric density in humans. Further studies are needed to determine whether WPC treatment has additional value to conventional antibiotic treatment for H pylori.

Commentary: metformin use is associated with reduced gastric cancer risk

Type 2 diabetes mellitus has been associated with increased all cancer incidence, including gastric cancer. Both hyperinsulinaemia and inflammatory changes secondary to adiposity have been suggested as important underlying mechanisms. 2 The debate of possible advantage or disadvantage of metformin, and other blood glucose lowering drugs, with regard to cancer risk is of great importance given the widespread use of these drugs. Recently, use of incretins was reported to cause no increased risk of pancreatic cancer. Metformin is generally considered the first-line drug for treating type 2 diabetes, and is one of the most commonly prescribed drugs worldwide. Previous population-based reports have suggested a preventive effect of metformin for liver, colorectal, pancreas, oesophageal and stomach cancers, although the available evidence is inconclusive. 5 The anti-carcinogenic effects of metformin have been attributed to several mechanisms, including activation of LKB1/AMPK pathway, induction of cell cycle arrest and/ or apoptosis, and activation of the immune system. Kim et al. report data from a Korean nationwide retrospective cohort study of type 2 diabetic patients. This interesting article, which is a valuable addition to the existing literature, reports a reduction in gastric cancer incidence among patients using metformin during more than 3 years, as compared to type 2 diabetic patients on other oral blood glucose lowering drugs. The relative risk of gastric cancer development among metformin users was reduced up to 43% (HR 0.57; 95% CI 0.37–0.87) after 3 years or more of metformin use. The nationwide data from a national insurance claim database support the validity of the association between metformin use and reduced gastric cancer incidence. However, duration of diabetes, and the need for switching to second-line oral therapies, are still important possible confounders for the reported association. Therefore, results of large randomised controlled trials are needed to finally elucidate this issue. In addition, with regard to clinical implications, and specifically the development of preventive medical strategies for gastric cancer, the preventive effect of metformin use will most certainly still be inferior to the importance of Helicobacter pylori eradication.

Practice patterns for achalasia – room for improvement?

SIRS, We read with interest the paper by Enestvedt et al. on epidemiology and management of achalasia in a large US multi-centre database. The article is informative and reaches the high standards of this excellent research group. As with any good article, it raises discussion that may shed further light on this interesting issue. Firstly, the authors describe achalasia patients diagnosed by endoscopy. More suitable diagnostic methods are manometry and barium esophagram, while endoscopy excludes secondary achalasia, and allows provision of therapy. This raises the question as to which proportion of patients in the CORI study was assessed by other methods and which proportion of patients was assessed by endoscopy alone. Secondly, the authors observed that botox has become the primary therapy and that at least one quarter of patients needed re-treatment every 14 months. These data ask for perspective. Botox is easy to apply and safe but with little evidence supporting long-term efficacy. The authors refer to a Cochrane review. This included 90 patients followed for 12 months, with a 74% recurrence after botox injection vs. 30% after pneumatic dilation (P = 0.002, RR 2.7, 95% CI 1.6–4.5). Botox is thus ineffective for sustained symptom relief and frequently necessitates retreatment which increases costs and complication risk. We recently described 336 achalasia patients treated at baseline with three consecutive pneumatic dilations with increasing balloon diameter up to 40 mm. During 985 pneumatic dilations, the perforation risk was 1%, the need for surgery 0.2% and mortality was 0%. With this baseline treatment, 33% of patients required re-treatment during a median follow-up of 10 years. In a recent randomised European study, laparoscopic myotomy and pneumatic dilation had similar results at 2-year follow-up. With this background, we wonder whether the authors are willing to conclude that there is room for improvement of achalasia treatment, which might include restriction of the use of botox as first-line treatment.

Subcutaneous rather than intravenous ustekinumab induction is associated with comparable circulating drug levels and early clinical response: a pilot study

Ustekinumab (USK) is licenced for intravenous induction and subcutaneous (S/C) maintenance in Crohns disease.