In the context of cancer diagnosis and treatment, we consider the problem of constructing an accurate prediction rule on the basis of a relatively small number of tumor tissue samples of known type containing the expression data on very many (possibly thousands) genes. Recently, results have been presented in the literature suggesting that it is possible to construct a prediction rule from only a few genes such that it has a negligible prediction error rate. However, in these results the test error or the leave-one-out cross-validated error is calculated without allowance for the selection bias. There is no allowance because the rule is either tested on tissue samples that were used in the first instance to select the genes being used in the rule or because the cross-validation of the rule is not external to the selection process; that is, gene selection is not performed in training the rule at each stage of the cross-validation process. We describe how in practice the selection bias can be assessed and corrected for by either performing a cross-validation or applying the bootstrap external to the selection process. We recommend using 10-fold rather than leave-one-out cross-validation, and concerning the bootstrap, we suggest using the so-called .632+ bootstrap error estimate designed to handle overfitted prediction rules. Using two published data sets, we demonstrate that when correction is made for the selection bias, the cross-validated error is no longer zero for a subset of only a few genes.

/pdf/selection-bias-in-gene-extraction-on-the-basis-of-microarray-3melvwlrf0.pdf

Selection bias in gene extraction on the basis of microarray gene-expression data.

http://www.antimicrobe.org/h04c.files/history/H.%20Pylori-Chey%20et%20al,%20AmJGastro%20Epub%2006-07.pdf

American College of Gastroenterology guideline on the management of Helicobacter pylori infection.

Description: A multidisciplinary group of 34 experts from 15 countries developed this update and expansion of the recommendations on the management of acute nonvariceal upper gastrointestinal bleeding (UGIB) from 2003. Methods: The Appraisal of Guidelines for Research and Evaluation (AGREE) process and independent ethics protocols were used. Sources of data included original and published systematic reviews; randomized, controlled trials; and abstracts up to October 2008. Quality of evidence and strength of recommendations have been rated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Recommendations: Recommendations emphasize early risk stratification, by using validated prognostic scales, and early endoscopy (within 24 hours). Endoscopic hemostasis remains indicated for high-risk lesions, whereas data support attempts to dislodge clots with hemostatic, pharmacologic, or combination treatment of the underlying stigmata. Clips or thermocoagulation, alone or with epinephrine injection, are effective methods; epinephrine injection alone is not recommended. Second-look endoscopy may be useful in selected high-risk patients but is not routinely recommended. Preendoscopy proton-pump inhibitor (PPI) therapy may downstage the lesion; intravenous high-dose PPI therapy after successful endoscopic hemostasis decreases both rebleeding and mortality in patients with high-risk stigmata. Although selected patients can be discharged promptly after endoscopy, high-risk patients should be hospitalized for at least 72 hours after endoscopic hemostasis. For patients with UGIB who require a nonsteroidal anti-inflammatory drug, a PPI with a cyclooxygenase-2 inhibitor is preferred to reduce rebleeding. Patients with UGIB who require secondary cardiovascular prophylaxis should start receiving acetylsalicylic acid (ASA) again as soon as cardiovascular risks outweigh gastrointestinal risks (usually within 7 days); ASA plus PPI therapy is preferred over clopidogrel alone to reduce rebleeding.

International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding

Improved survival after variceal bleeding in patients with cirrhosis over the past two decades.

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) was originally discovered in the late 1970s because of its capacity to increase the permeability of microvessels to plasma and plasma proteins (Dvorak et al 1979a,b) Using plastic-embedded, light microscopic section and, subsequent, immunohistochemistry, we noted that transplantable tumors growing in guinea pigs and rodents exhibit substantial deposits of fibrin in their stroma Fibrin results from the clotting of fibrinogen, a 340kDa plasma protein which, under normal circumstances, is retained almost quantitatively within the blood vasculature For fibrin to be deposited outside of blood vessels in tumor stroma, it was necessary that two requirements be met; namely, (1) that microvessels be abnormally hyperpermeable to permit the escape of fibrinogen and other plasma proteins necessary for blood clotting and (2) that there be a mechanism in place for activating the clotting system In fact, both requirements were found to be met in tumors The microvessels supplying tumors were hyperpermeable to fibrinogen and other plasma proteins, and both tumor cells and host stromal cells were capable of initiating extravascular coagulation via the tissue-factor pathway Encouraged by these findings, we initiated a search for a tumor product that could account for tumor-vessels hyperpermeability A potent vascular permeabilizing protein was soon found in serum-free tumor culture supernatants (Dvorak et al 1979a,b) and was subsequently purified to homogeneity and given the name vascular permeability factor (VPF) (Senger et al 1983, 1986, 1987, 1990)

Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis.

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.510250509

Emergency banding ligation versus sclerotherapy for the control of active bleeding from esophageal varices

Expression of vascular endothelial growth factor in normal liver and hepatocellular carcinoma: an immunohistochemical study

Background:

Although the eradication of Helicobacter pylori infection benefits patients with gastric or duodenal ulcers, the value of eradicating the infection in the patients with functional dyspepsia (FD) remains controversial.



Aims:

To determine whether eradicating H. pylori can prevent the subsequent development of ulcers or relieve the symptoms of functional dyspepsia patients.



Methods:

In a double-blind, placebo-controlled trial, 161 patients infected with H. pylori who had functional dyspepsia were randomly assigned to 7 days of treatment with a lansoprazole-based triple therapy or placebo and then followed for 1 year. The main outcome measures were the development of peptic ulcers and the resolution of symptoms.



Results:

H. pylori was eradicated in 63 out of 81 patients (78%) in the treatment group and none of the 80 patients (0%) in the placebo group. During the follow-up period, two patients in the treatment group and six patients in the placebo group developed peptic ulcers at repeat endoscopy (2.5% vs. 7.5%; 95% CI: –12 to 2). The reduction in ulcer rates was statistically significant in the ‘ulcer-like’ sub-group (0% vs. 16.7%; 95% CI: –32 to –2), but not in the ‘dysmotility-like’ and ‘unclassifiable’ sub-groups. Regarding symptom response, the resolution rates of symptoms were similar between the treatment and placebo groups (58.0% vs. 55.0%, 95% CI: –12 to 18). Additionally, no significant differences existed in the symptom responses between the treatment and control arms in each of the dyspepsia sub-groups.



Conclusions:

Eradicating H. pylori can prevent the subsequent development of peptic ulcers in the patients with ‘ulcer-like’ functional dyspepsia. However, this approach does not significantly reduce the symptoms of functional dyspepsia patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2036.2001.00903.x

Eradication of Helicobacter pylori prevents ulcer development in patients with ulcer-like functional dyspepsia.

Endoscopic balloon dilatation is a safe method in the management of common bile duct stones

From September 1991 to December 1992, a prospective study was conducted to determine the risk factors and residual risk of rebleeding, and the evolutionary endoscopic changes in peptic ulcers that rebled. Emergency endoscopies were performed on 452 patients with haematemesis or a melaena, or both within 24 hours of admission. If the lesions were actively bleeding, then the patients were treated with injection sclerotherapy. A multivariate analysis of clinical, laboratory, and endoscopic variables of 204 patients with ulcer bleeding showed that hypovolaemic shock, a non-bleeding visible vessel, and an adherent clot on the ulcer base were independently significant in predicting rebleeding (p < 0.05). Considering these three factors according to the estimates of their regression coefficients showed that a non-bleeding visible vessel was the strongest predictor of rebleeding. The study of the residual risk of rebleeding after admission showed that most rebleeding episodes (94.1%), including all associated with hypovolaemic shock, surgical treatment, and death, occurred within 96 hours of admission. After this time, the residual risk of rebleeding was less than 1%. Study of the changes in endoscopic findings before and after rebleeding illustrated that all ulcers with a visible vessel or adherent clot showed at follow up endoscopy were derived from ulcers with initial major stigmata. It is concluded that hypovolaemic shock, a non-bleeding visible vessel, and an adherent clot on an ulcer base are of independent significance in predicting rebleeding. Observation for 96 hours is sufficient to detect most rebleeding episodes after an initial bleed from peptic ulcer.

https://gut.bmj.com/content/gutjnl/35/6/746.full.pdf

Hsu Pi

Papers

Emergency banding ligation versus sclerotherapy for the control of active bleeding from esophageal varices

Expression of vascular endothelial growth factor in normal liver and hepatocellular carcinoma: an immunohistochemical study

Eradication of Helicobacter pylori prevents ulcer development in patients with ulcer-like functional dyspepsia.

Endoscopic balloon dilatation is a safe method in the management of common bile duct stones

Bleeding peptic ulcer--risk factors for rebleeding and sequential changes in endoscopic findings.