M. G. H. van Oijen

Factors influencing the miss rate of polyps in a back-to-back colonoscopy study

BACKGROUND AND STUDY AIMS In patients undergoing colonoscopy, 22 % - 28 % of polyps and 20 % - 24 % of adenomas are missed. It is unclear which factors contribute to polyp miss rates, but colorectal cancer detected within 3 years after colonoscopy may originate from missed lesions. The aim of the current study was to determine patient- and polyp-related factors that influence the miss rates of polyps and adenomas during colonoscopy. PATIENTS AND METHODS Data from 406 patients were obtained from a multicenter, randomized back-to-back colonoscopy study investigating the Third Eye Retroscope (TER) in improving polyp detection rate by visualizing hidden areas such as folds and curves. Patients were randomized to undergo standard colonoscopy followed by colonoscopy with TER, or vice versa. Miss rates were calculated for all polyps and adenomas. All lesions were categorized for size and location within the colon/rectum. Odds ratios (ORs) were computed using adjusted logistic regression models to identify factors independently associated with missed lesions. RESULTS The miss rate was 25 % (150 /611) for all polyps and 26 % (90 /350) for adenomas. Miss rates were significantly lower (21 % vs. 29 %) in patients randomized to TER as the first procedure (P < 0.03). Taking all groups together, > 2 polyps compared with ≤ 2 polyps detected during the first colonoscopy increased the risk of missing additional polyps (adjusted OR = 2.83; 95 % confidence interval [CI] 1.22 - 6.70). Adenomas in the left colon compared with adenomas in the right colon were also more frequently missed (adjusted OR = 1.65; 95 %CI 1.06 - 2.58). CONCLUSIONS A quarter of polyps were missed during colonoscopy. Physicians should be aware that the risk of missing a polyp is related to patient factors (presence of > 2 polyps) and polyp factors (left colon location).

Proton pump inhibitor therapy predisposes to community-acquired Streptococcus pneumoniae pneumonia.

The pathophysiological mechanisms which contribute to an increased risk of community‐acquired pneumonia (CAP) in patients using proton pump inhibitors are not well established.

Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis

BACKGROUND The recent expanding technical possibilities to detect tumor derived mutations in blood, so-called circulating tumor DNA (ctDNA), has rapidly increased the interest in liquid biopsies. This review and meta-analysis explores the clinical value of ctDNA in malignancies of the upper gastro-intestinal tract. METHODS PubMed, Cochrane and Embase databases were searched to identify studies reporting the diagnostic, prognostic or predictive value of ctDNA in patients with esophageal, gastric and pancreatic cancer, until January 2017. The diagnostic accuracy and, using random-effect pair-wise meta-analyses, the prognostic value of ctDNA was assessed. RESULTS A total of 34 studies met the inclusion criteria. For esophageal and gastric cancer, amplification of oncogenes in blood, such as HER2 and MYC, can be relevant for diagnostic purposes, and to predict treatment response in certain patient subpopulations. Given the limited number of studies assessing the role of ctDNA in esophageal and gastric cancer, the meta-analysis estimated the diagnostic accuracy and predictive value of ctDNA in pancreatic cancer only (n=10). The pooled sensitivity and specificity of ctDNA as a diagnostic tool in pancreatic cancer were 28% and 95%, respectively. Patients with pancreatic cancer and detectable ctDNA demonstrated a worse overall survival compared to patients with undetectable ctDNA (HR 1.92, 95% confidence interval (CI) 1.15-3.22, p=0.01). CONCLUSION The presence of ctDNA is significantly associated with a poor prognosis in patients with pancreatic cancer. The use of ctDNA in clinical practice is promising, although standardization of sequencing techniques and further development of high-sensitive detection methods is needed.

Different seasons with decreased performance of immunochemical faecal occult blood tests in colorectal cancer screening

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Adding familial risk assessment to faecal occult blood test can increase the effectiveness of population-based colorectal cancer screening

BACKGROUND The Dutch Health Council recently recommended the introduction of a colorectal cancer (CRC) screening programme by faecal occult blood testing (FOBT) for individuals aged 55-75 at population risk of CRC. Individuals at an increased familial CRC risk (≥ 2 times population risk) should be identified at a younger age, so they and their relatives can receive earlier, more intensive surveillance instead of FOBT. AIMS To determine the percentage of participants with a positive FOBT in a CRC screening programme with an increased familial CRC risk. METHODS In a population-based study, 10,569 individuals aged 50-75 received an FOBT. Individuals with a positive FOBT were invited for colonoscopy and familial risk assessment. Participants with an average familial CRC risk were compared to those with an increased risk. Increased familial CRC risk was defined as a cumulative lifetime risk of CRC of at least 10%. RESULTS Of 6001 participants, 430 had a positive FOBT, of whom 324 (63% males; mean age 63 years) completed colonoscopy and familial risk assessment. CRC (n=22) and/or advanced adenomas (n=122) were found in 133 participants. Familial CRC risk was increased in 6% of participants with a positive FOBT. No significant differences were found between participants with an average versus an increased familial CRC risk. CONCLUSION Six percent of participants with a positive FOBT had an increased familial CRC risk. Identifying at-risk participants enables them and their relatives to undergo regular colonoscopies. Adding familial risk assessment to FOBT screening may thus prevent a substantial number of CRCs.

Prediction models for patients with esophageal or gastric cancer: A systematic review and meta-analysis

Background Clinical prediction models are increasingly used to predict outcomes such as survival in cancer patients. The aim of this study was threefold. First, to perform a systematic review to identify available clinical prediction models for patients with esophageal and/or gastric cancer. Second, to evaluate sources of bias in the included studies. Third, to investigate the predictive performance of the prediction models using meta-analysis. Methods MEDLINE, EMBASE, PsycINFO, CINAHL, and The Cochrane Library were searched for publications from the year 2000 onwards. Studies describing models predicting survival, adverse events and/or health-related quality of life (HRQoL) for esophageal or gastric cancer patients were included. Potential sources of bias were assessed and a meta-analysis, pooled per prediction model, was performed on the discriminative abilities (c-indices). Results A total of 61 studies were included (45 development and 16 validation studies), describing 47 prediction models. Most models predicted survival after a curative resection. Nearly 75% of the studies exhibited bias in at least 3 areas and model calibration was rarely reported. The meta-analysis showed that the averaged c-index of the models is fair (0.75) and ranges from 0.65 to 0.85. Conclusion Most available prediction models only focus on survival after a curative resection, which is only relevant to a limited patient population. Few models predicted adverse events after resection, and none focused on patient’s HRQoL, despite its relevance. Generally, the quality of reporting is poor and external model validation is limited. We conclude that there is a need for prediction models that better meet patients’ information needs, and provide information on both the benefits and harms of the various treatment options in terms of survival, adverse events and HRQoL.

Discordance in HER2 Status in Gastro-esophageal Adenocarcinomas: A Systematic Review and Meta-analysis

Trastuzumab combined with chemotherapy is standard of care for HER2 positive advanced gastro-esophageal cancers. The reported prevalence of HER2 discordance between primary tumors and corresponding metastases varies, hampering uniform patient selection for HER2 targeted therapy. This meta-analysis explores the influence of HER2 assessment methods on this discordance and investigates the prevalence of HER2 discordance in gastro-esophageal adenocarcinomas. PubMed, Embase and Cochrane databases were searched until January 2016. Differences in discordance rate between strict and broad(er) definitions of HER2 status were assessed using random-effect pair-wise meta-analysis. Random-effect single-arm meta-analyses were performed to assess HER2 discordance and the prevalence of positive and negative conversion. A significantly lower discordance rate in HER2 status between primary tumors and corresponding metastases was observed using a strict vs. broad definition of HER2 status (RR = 0.58, 95%CI 0.41–0.82), with a pooled discordance rate of 6.2% and 12.2%, respectively. Using the strict definition of HER2 assessment pooled overall discordance was 7% (95%CI 5–10%). The lowest discordance rates between primary tumors and corresponding metastasis are observed when using a strict method of HER2 positivity. Treatment outcomes of different studies will be better comparable if selection of eligible patients for HER2 targeted therapy is based on this strict definition.