Cost-effectiveness analysis of single colonoscopy versus single fecal test for colorectal cancer diagnosis and treatment.

BACKGROUND AND AIM: Regular endoscopy or fecal immunochemical test (FIT) is ideal for screening colorectal cancer. However, only a limited number of individuals undergo regular screening. This study aimed to compare the cost-effectiveness of a single colonoscopy with a single FIT performed for colorectal cancer screening. METHODS: A microsimulation model was constructed based on real-world observational data collected from three institutions between 2019 and 2022 that compared colonoscopy-based screening with FIT-based screening. The total costs of diagnosis and treatment of the detected lesions using the two strategies were calculated. The incremental cost-effectiveness ratio (ICER) per life year gained (LYG) of the colonoscopy-based strategy was calculated. RESULTS: Data from 11 407 patients undergoing colonoscopies and 59 176 patients undergoing FITs were used to establish a model. In the base case analysis of screening strategies, colonoscopy was more cost-effective than FIT (ICER 415 193 yen/LYG). The ICER of the colonoscopy-based strategy among 60- to 69-year-old patients was lowest at 394 200 yen/LYG, whereas that in 20- to 29-year-old patients was highest. Monte Carlo simulations showed that the colonoscopy-based strategy was more cost-effective than the FIT-based strategy (net monetary benefit [NMB]: 5 695 957 yen vs 5 348 253 yen). When the adenoma detection rate in the colonoscopy was over 30% or the positive FIT rate was lower than 8.6% in the FIT-based strategy, the NMB of the colonoscopy-based strategy exceeded that of the FIT-based strategy. CONCLUSION: In the microsimulation model, colonoscopy is recommended as a one-time screening procedure in patients aged >60 years with >30% ADR or <8.6% positive FIT rate.

An algorithm-based active cleansing protocol can reduce the bowel preparation time for screening colonoscopy: A propensity score matching study.

BACKGROUND: Methods that minimize the time for on-site bowel preparation before colonoscopy are needed. We prospectively validated that a novel algorithm-based active cleansing (ABAC) protocol could reduce the time for preparation compared with the conventional method. METHODS: This was an open-label, multicenter, prospective comparative study from April to October 2021. The study compared the bowel preparation time for colonoscopy between patients instructed with the ABAC protocol and control groups. Patients in the ABAC protocol group as well as the control group were administered 2000 mL of polyethylene glycol (PEG) within 2 hours. After the first two hours, patients in the protocol group voluntarily took 300 ml of the solution without the instruction of nursing staff depending on the number of defecations in the first 2 hours. The intervention and control groups were adjusted for background characteristics by propensity score matching (PSM). RESULTS: After adjustment by PSM, 174 patients in each of the two groups were included in the final analysis. In the intention-to-treat analysis, the preparation time was significantly shorter in the intervention group than that in the control group (126.3 ± 32.7 min vs. 144.9 ± 39.9 min, P = 0.018). The proportion of additional PEG intake was significantly higher in the intervention group (16 [9.2%] vs. 6 [3.4%], P = 0.047). The number of defecations was also higher in the intervention group than in the control group (7.8 ± 2.5 vs. 6.3 ± 2.2, P = 0.001). CONCLUSIONS: Simple active instruction protocol is effective to reduce on-site bowel preparation time and nursing staff labor for colonoscopy.

Dietary restriction after cold snare polypectomy of colorectal polyp for prevention of delayed bleeding.

Background and Aim: Cold snare polypectomy (CSP) for small colorectal polyps is a safe technique; however, there is little evidence on whether dietary restriction after CSP is essential. This study aimed to determine whether dietary restriction after CSP is necessary to prevent delayed bleeding. Methods: This is a randomized, controlled, non-inferiority trial conducted between November 2021 and March 2022. Patients with non-pedunculated small colorectal polyps (<10 mm) and who did not take anticoagulants were randomly allocated to two groups: (i) the normal diet (ND) group, and (ii) the low-residue diet (LRD) group. The ND group was instructed to eat anything after CSP, whereas the LRD group was advised to take LRD for 3 days after CSP. The primary endpoint was the occurrence of delayed major bleeding that needed endoscopic hemostasis. Results: A total of 193 patients (average 57.5 years old, 51.9% male) were enrolled in the study. Subsequently, 97 and 96 patients were allocated to the ND and LRD group, respectively. The occurrence of delayed major bleeding was 1.0% in the ND group and 2.1% in the LRD group (95% confidence interval [CI]: -4.4% to 2.4%; difference: -1.1%), which showed the non-inferiority of the ND group. In addition, there was no difference between the two groups with respect to the occurrence of minor delayed bleeding (3.1% and 4.2%, respectively; difference: -1.1% [95% CI: -6.4% to 4.2%]). Conclusion: Dietary restriction after CSP for low-bleeding-risk colorectal polyps is not necessary for the prevention of delayed bleeding (Registration number: UMIN000045669).

Detecting colorectal lesions with image-enhanced endoscopy: an updated review from clinical trials.

Colonoscopy plays an important role in reducing the incidence and mortality of colorectal cancer by detecting adenomas and other precancerous lesions. Image-enhanced endoscopy (IEE) increases lesion visibility by enhancing the microstructure, blood vessels, and mucosal surface color, resulting in the detection of colorectal lesions. In recent years, various IEE techniques have been used in clinical practice, each with its unique characteristics. Numerous studies have reported the effectiveness of IEE in the detection of colorectal lesions. IEEs can be divided into two broad categories according to the nature of the image: images constructed using narrowband wavelength light, such as narrowband imaging and blue laser imaging/blue light imaging, or color images based on white light, such as linked color imaging, texture and color enhancement imaging, and i-scan. Conversely, artificial intelligence (AI) systems, such as computer-aided diagnosis systems, have recently been developed to assist endoscopists in detecting colorectal lesions during colonoscopy. To better understand the features of each IEE, this review presents the effectiveness of each type of IEE and their combination with AI for colorectal lesion detection by referencing the latest research data.

Optimizing Helicobacter pylori Treatment: An Updated Review of Empirical and Susceptibility Test-Based Treatments.

As the rate of discovery of drug-resistant Helicobacter pylori cases increases worldwide, the relevant societies have updated their guidelines for primary eradication regimens. A promising strategy against drug-resistant H. pylori is tailored therapy based on the results of an antibiotic susceptibility test; however, it is difficult to apply this strategy to all cases. Although culture-based antibiotic susceptibility tests can assess resistance to any antimicrobial agent, their greatest disadvantage is the time required to draw a conclusion. In contrast, molecular-based methods, such as polymerase chain reaction, can rapidly determine the presence of resistance, although a single test can only test for one type of antimicrobial agent. Additionally, the limited availability of facilities for molecular-based methods has hindered their widespread use. Therefore, low-cost, minimally invasive, simple, and effective primary regimens are needed. Several studies have compared the efficacy of the latest primary eradication regimens against that of tailored therapies, and their results have shaped guidelines. This article reviews the latest research on empirical and tailored treatments for H. pylori infections. Evidence for the superiority of tailored therapy over empirical therapy is still limited and varies by region and treatment regimen. A network meta-analysis comparing different empirical treatment regimens showed that vonoprazan triple therapy provides a superior eradication effect. Recently, favorable results towards vonoprazan dual therapy have been reported, as it reached eradication levels similar to those of vonoprazan triple therapy. Both vonoprazan dual therapy and tailored therapy based on antibiotic susceptibility tests could contribute to future treatment strategies.

Colorectal cold snare polypectomy: Current standard technique and future perspectives.

It has been shown that resection of adenomatous colorectal polyps can reduce mortality due to colorectal cancer. In daily clinical practice, simpler and safer methods of colorectal polypectomy have been sought to enable endoscopists to resect all detected lesions. Among these, cold snare polypectomy (CSP) is widely used in clinical practice because of its advantages in shortening procedure time, reducing delayed bleeding risk, and lowering treatment costs, while maintaining a similar complete resection rate for lesions smaller than 10 mm when compared to conventional hot snare polypectomy. This review introduces the findings of previous studies that investigated the efficacy and safety of the CSP procedure for nonpedunculated polyps smaller than 10 mm, and describes technical points to remember when practicing CSP based on the latest evidence, including using a thin wire snare specifically designed for CSP, and observing the surrounding mucosa of the resection site with chromoendoscopy or image-enhanced endoscopy to ensure that there is no residual lesion. This review also describes the potential of expanding the indication of CSP as a treatment for lesions larger than 10 mm, those with pedunculated morphology, those located near the appendiceal orifice, and for patients under continuous antithrombotic agent therapy. Finally, the perspective on optimal treatments for recurrent lesions after CSP is also discussed, despite the limited related evidence and data.

A Close Follow-Up Strategy in the Short Period of Time after Helicobacter pylori Eradication Contributes to Earlier Detection of Gastric Cancer.

INTRODUCTION: The purpose of this study was to optimize the surveillance frequency and period for efficient detection of early gastric cancer (EGC) after Helicobacter pylori (HP) eradication. METHODS: Data from patients with eradicated HP infection were extracted from the endoscopy databases of two institutions from January 2016 to March 2021. The patients were divided into a close follow-up group with frequent surveillance after eradication and an open follow-up group with an intermittent surveillance method, and the cases of post-eradication EGC found in the two groups were analyzed. RESULTS: Thirty-six out of 9,322 patients (0.39%) in the close follow-up group and 20 out of 11,436 patients (0.17%) in the open follow-up group were found to have EGC. The cumulative incidence of EGC after eradication was significantly higher in the close follow-up group (p = 0.004). The duration between eradication and EGC detection was significantly shorter in the close follow-up group (51.7 vs. 90.5 months, p = 0.002). A logistic regression model revealed that duration after eradication was an independent predictor for detecting EGC in the close follow-up group (p = 0.045). A Cox proportional hazards model revealed that the close follow-up strategy was effective in patients with an eradication duration of less than 65 months to identify EGC (p = 0.015), but there was no difference between the two strategies in patients with an eradication duration of more than 65 months (p = 0.624). DISCUSSION/CONCLUSIONS: Frequent surveillance after HP eradication is efficient for the early detection of EGC during the first 65 months.

A delay in the diagnosis of colorectal cancer screened by fecal immunochemical tests during the COVID-19 pandemic: a longitudinal cohort study.

PURPOSE: There is concern that the COVID-19 pandemic may cause people to refrain from undergoing examination resulting in delayed detection of colorectal cancer (CRC). The purpose of this study was to investigate whether there was a delay in CRC detection due to withholding of screening. METHODS: The colonoscopy screening rate and the CRC detection rate were calculated for patients who underwent fecal immunochemical tests (FITs) from 2018 to 2021 in the longitudinal cohort. The stages of CRC cases detected as a result of positive FIT in each year were compared. RESULTS: A total of 39,521 patients were initially screened by FIT over a 4-year period. The FIT-positive rate was 4.7% (441 /9,349) in 2018, 4.6% (420 /9,156) in 2019, 4.9% (453 /9,255) in 2020, and 4.3% (504 /11,760) in 2021. The colonoscopy screening rate for positive FIT results was lower in 2020 than in 2019 (25.8% vs. 38.1%, P < 0.001), and higher in 2021 than in 2020 (56.7% vs. 25.8%, P < 0.001). The CRC detection rate among colonoscopy recipients was higher in 2021 than in 2020 (13% vs. 4%, P = 0.014). Stage 1 or higher CRC accounted for 25.0% (1/4) in 2020, and 78% (18/23) in 2021. Among the CRC cases detected each year, 1 (14%), 1 (25%), and 10 (43%) did not undergo colonoscopy despite positive FIT results in the previous year. CONCLUSIONS: The COVID-19 pandemic has reduced the detection of CRC by screening colonoscopy following FIT and might have led to a delay in the detection of CRC.

[Concurrent chemoradiotherapy with carboplatin and docetaxel for stage III non-small-cell lung cancer].

The efficacy and toxicity of concurrent chemoradiotherapy with carboplatin (AUC=5) +docetaxel (70 mg/m(2)) were analyzed retrospectively in 20 patients with stage III non-small-cell lung cancer (NSCLC). The median age of the patients was 65 years (range, 53-73 years). The performance status (ECOG), clinical stage, and tumor histology of the patients were as follows: PS: PS 0, 12 patients; PS 1, 8 patients; disease stage: stage III A, 6 patients; stage III B, 14 patients; tumor histology: adenocarcinoma, 11 patients; squamous cell carcinoma, 6 patients; large cell carcinoma, 3 patients. The median number of treatment courses administered was 4. The median survival time was 23 months, and the 2-year survival rate was 50%. The median progression free survival was 17.5 months. The response rate was 75%. Common toxicities included grade 3/4 neutropenia (95%), grade 3 esophagitis (5%), grade 3 anorexia (30%), grade 3 febrile neutropenia (35%) and grade 5 radiation pneumonitis (5%). Further studies are warranted to evaluate the efficacy and toxicity of this regimen.

Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status.

BACKGROUND: The clinical significance of Helicobacter pylori antibody titer has been controversial, and the association between the extent of gastric atrophy or acid secretion and H. pylori antibody concentration has not been elucidated. MATERIALS AND METHODS: Serum pepsinogen, H. pylori antibody concentration, and fasting gastric pH (as an indicator of acid secretion) were measured in 231 patients undergoing upper gastrointestinal endoscopy. "Atrophic" pepsinogen was defined as pepsinogen-I < 70 ng/mL and pepsinogen-I/II ratio < 3. Other levels of pepsinogen were defined as "normal". Fasting gastric pH was analyzed in subjects stratified by pepsinogen level and by H. pylori antibody concentration. RESULTS: Helicobacter pylori antibody concentration showed no significant relationship with fasting gastric pH when all subjects were analyzed together. In H. pylori-seronegative subjects, fasting gastric pH was within the normal range, irrespective of the extent of mucosal atrophy. In H. pylori-seropositive subjects, H. pylori antibody concentration was positively correlated with fasting gastric pH in subjects with "normal" pepsinogen, but inversely correlated in those with "atrophic" pepsinogen. Particularly in subjects with low H. pylori antibody concentration and atrophic mucosa, a group reportedly at high risk of noncardia cancer, the most impaired acid secretion was shown among subjects with atrophic mucosa. CONCLUSIONS: The relationship between acid secretion and H. pylori antibody concentration differs depending on the presence of mucosal atrophy. Our findings provide a possible rationalization for measuring both serum pepsinogen levels and H. pylori antibody concentration in gastric cancer screening.

Serum nitrate/nitrite concentration correlates with gastric juice nitrate/nitrite: a possible marker for mutagenesis of the proximal stomach.

BACKGROUND/AIMS: In the normal acid-secreting stomach, luminally generated nitric oxide, which contributes to carcinogenesis in the proximal stomach, is associated with the concentration of nitrate plus nitrite (nitrate/nitrite) in gastric juice. We investigated whether the serum nitrate/nitrite concentration is associated with that of gastric juice and whether it can be used as a serum marker. METHODS: Serum and gastric juice nitrate/nitrite concentration, Helicobacter pylori antibody, and gastric pH were measured in 176 patients undergoing upper endoscopy. RESULTS: Multiple regression analysis revealed that serum nitrate/nitrite concentration was the best independent predictor of gastric juice nitrate/nitrite concentration. On single regression analysis, serum and gastric juice nitrate/nitrite concentration were significantly correlated, according to the following equation: gastric juice nitrate/nitrite concentration (µmol/l) = 3.93 - 0.54 × serum nitrate/nitrite concentration (µmol/l; correlation coefficient = 0.429, p < 0.001). In analyses confined to subjects with gastric pH less than 2.0, and in those with serum markers suggesting normal acid secretion (pepsinogen-I >30 ng/ml and negative H. pylori antibody), the serum nitrate/nitrite concentration was an independent predictor of the gastric juice nitrate/nitrite concentration (p < 0.001). CONCLUSION: Measuring the serum nitrate/nitrite concentration has potential in estimating the gastric juice nitrate/nitrite concentration. The serum nitrate/nitrite concentration could be useful as a marker for mutagenesis in the proximal stomach.

[A case of advanced adenocarcinoma of the lung which maintained complete response for 5 years by treatment with gefitinib].

A 73-year-old woman smoker presented with dyspnea on exertion due to massive left pleural effusion. A CT scan after drainage of the pleural effusion demonstrated a nodule in the left lung, and cytology of the pleural effusion showed adenocarcinoma. We diagnosed advanced adenocarcinoma of the lung, and clinical stage IIIB. Chemotherapy with carboplatin and docetaxel was discontinued after the second course because of anorexia, and gefitinib was administered from October 2004. The lung nodule and pleural effusion had disappeared on CT by November 2004. A complete response continued for 5 years. We report a 5-year complete response in a case of advanced adenocarcinoma of the lung by treatment with gefitinib.

ADAMTS5 is a biomarker for prediction of response to infliximab in patients with rheumatoid arthritis.

OBJECTIVE: To identify a biomarker for prediction of the response to infliximab (IFX) in patients with rheumatoid arthritis (RA), we focused on a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) that seems to play a key role in aggrecan degradation in cartilage. METHODS: Seventy-three randomly selected patients with active RA were treated with IFX. Peripheral blood samples were collected at baseline and ADAMTS5 messenger RNA (mRNA) was quantified using real-time polymerase chain reaction. RESULTS: Baseline ADAMTS5 mRNA levels in the good responder group were significantly lower (1.84 +/- 1.56; p = 0.0408) than those in the moderate and nonresponder groups (2.54 +/- 1.70) at 38 weeks of treatment with IFX. The 28-joint count Disease Activity Score (DAS28) at 38 weeks of treatment was significantly lower in the low ADAMTS5 group (2.30 +/- 1.28; p = 0.0038) than in the high ADAMTS5 group (3.90 +/- 1.61). The percentage reduction of the DAS28 was significantly higher in the low ADAMTS5 group (52.5% +/- 28.8%; p = 0.0156) than in the high ADAMTS5 group (29.4% +/- 27.2%). Further, the Delta Health Assessment Questionnaire (DeltaHAQ) score, an estimate of the improvement in the HAQ score, at 38 weeks of treatment was significantly higher in the low ADAMTS5 group (1.18 +/- 0.60; p = 0.0102) than in the high ADAMTS5 group (0.21 +/- 0.78). The positive predictive value of a low baseline ADAMTS5 level for predicting good response and remission (DAS28 < 2.6 at 38 weeks) was 90.0% and 70.0%, respectively. CONCLUSION: The baseline ADAMTS5 mRNA level is a candidate biomarker for prediction of the response to IFX in patients with RA.

[A case of miliary tuberculosis showing acute respiratory distress syndrome in rheumatoid arthritis].

A 62-year-old man, treated with corticosteroids and immunosuppressants for rheumatoid arthritis, visited hospital with high fever and dyspnea on exertion. A CT scan of the chest demonstrated bilateral diffuse ground glass opacities. On the basis of the findings of the CT scan, he was initially given a diagnosis of interstitial pneumonia. He was then referred to our hospital and admitted to the intensive care unit (ICU), where because of progressive respiratory failure, he was put on mechanical ventilation. A bronchoscopy specimen after intubation turned out to be positive for acid-fast bacilli, which were confirmed to be mycobacterium tuberculosis by a polymerase chain reaction test. He was given a diagnosis of miliary tuberculosis complicated with acute respiratory distress syndrome (ARDS). He died of respiratory failure despite treatment with antituberculosis drugs. The autopsy revealed necrotizing epithelioid granulomas in both lungs, mediastinal lymph nodes, the liver, both kidneys, vertebrae and other organs. Diffuse alveolar damage was also found in both lungs. It is often difficult to detect disseminated nodules in the miliary tuberculosis with ARDS. Miliary tuberculosis should be suspected in patients in an immunosuppressant state with rheumatoid arthritis, and who have respiratory symptoms or fever of unknown origin.

[A case of adult intussusceptions with multiple colon cancer].

A 64-year-old woman visited our outpatient clinic because of bloody stools and abdominal fullness. Digital rectal examination revealed a 6 x 4-cm oval mass. Abdominal CT scans demonstrated a concentric, multilayered structure in the rectum. Colonoscopy showed segments of the bowel were dark-purplish, and intussusception. Deeper insertion of the colonoscope through the lumen revealed a type 1 lesion. Under a diagnosis of sigmoid colon cancer with intrarectal intussusception, emergency surgery was performed. The resected specimen showed a type 1 advanced cancer and two early cancers at the base of the intussuscepted colon, all of which appear to have contributed to the intussusception.

Prediction of fasting gastric pH using serum biological markers.

BACKGROUND/AIMS: Previous studies have suggested that hypochlorhydria has the potential to produce adverse effects such as the development of infections of the intestinal or respiratory tract and impaired drug absorption. This indicates the importance of obtaining a noninvasive method by which this condition may be diagnosed. The purpose of this study was to determine whether fasting gastric pH could be predicted noninvasively using serum biological markers. METHODOLOGY: One hundred thirty-two patients undergoing diagnostic upper gastrointestinal endoscopy were recruited. Serum levels of pepsinogen-I, pepsinogen-II and Helicobacter pylori antibody were analyzed and the pH of fasting gastric juice determined. Multiple linear regression analysis was used to determine the best predictors of fasting gastric pH. RESULTS: Pepsinogen-I and the presence of Helicobacter pylori were independent predictors of fasting gastric pH, and a high coefficient of determination was obtained (R2 = 0.503, root mean square error = 1.45). The equation for this model was as follows: fasting gastric pH = 2.97-0.026 (pepsinogen-I)+2.76 (presence of Helicobacter pylori: 0=absent, 1=present). CONCLUSIONS: The model equation offers a noninvasive method by which to identify patients at high-risk of developing complications induced by hypochlorhydria.

Lipopolysaccharides stimulate adrenomedullin synthesis in intestinal epithelial cells: release kinetics and secretion polarity.

Adrenomedullin (AM), a potent vasodilator peptide initially isolated from a human pheochromocytoma, functions as an antimicrobial peptide in host defense. In this study, we investigated changes in AM levels in intestinal epithelial cells and the mechanism of its secretion and cellular polarity after exposure to lipopolysaccharides (LPS). When a rat small intestinal cell line (IEC-18 cells) was exposed to LPS, enzyme-linked immunosorbent assay revealed a dose-dependent increase in AM together with an increase in AM mRNA expression, as determined by real-time polymerase chain reaction. Up-regulation of AM by LPS was dose-dependently inhibited by LY294002, PD98059, SP600125 and calphostin-C, suggesting the involvement of the phosphatidylinositol 3 kinase, extracellular signal-regulated kinase, c-Jun NH2-terminal kinase and protein kinase C pathways, respectively, in this process. When polarized IEC-18 cells in a Transwell chamber were stimulated with LPS, AM secretion was directed primarily toward the side of LPS administration (either the apical or basolateral side). In situ hybridization revealed that AM mRNA was expressed in epithelial cells and in the connective tissue in the lamina propria of the jejunum after intraperitoneal or oral administration of LPS. Higher levels of AM mRNA expression were observed in rats treated with LPS via the intraperitoneal route, compared with those treated via the oral route. These findings suggest that intestinal AM plays an important role in mucosal defense in the case of intestinal luminal infection, as well as in the modulation of hemodynamics in endotoxemia.

[A case of early-onset COPD with recurrent pneumothorax].

Early-onset chronic obstructive pulmonary disease (COPD) is designated as onset under age 50. We report a case of early-onset COPD with recurrent pneumothorax. A 29-year-old woman visited our hospital with productive cough and dyspnea on exertion. CT scan of the chest demonstrated severe panlobular emphysema. A pulmonary function test showed a reduction in FEV1.0 (41% of the predicted value). A diagnosis of severe COPD was made. Her symptoms and pulmonary function improved after the treatment of inhaled corticosteroid, long-acting beta2-agonist, and anti-cholinergic drugs. She had pneumothorax at least 8 times in the right lung. The level of alpha1-antitrypsin was normal. On the basis of the characteristics of the appearance of the chest X-ray and CT scan, the possibility of bronchiolitis obliterans, lymphoangioleiomyomatosis or Langerhans cell histiocytosis was thought to be low. We considered that several factors, such as high susceptibility, pulmonary infection during her childhood, bronchial asthma, malnutrition, smoking history from an early age, and long-term passive exposure to cigarette smoke may have contributed to the development of early-onset COPD in the present case.