Effects of ranitidine and nizatidine on the risk of gastrointestinal cancer.

Purpose: Gastrointestinal (GI) cancer occurs in digestive organs such as the stomach, colon, liver, esophagus, and pancreas. About 83,034 cases occurred in Korea alone in 2020. Dietary factors, alcohol consumption, Helicobacter pylori (H. pylori), and lifestyle factors increase the incidence of diseases such as gastritis, peptic ulcer, pancreatitis, and gastroesophageal reflux disease (GERD), which can develop into GI cancer. However, in 2019, the US Food and Drug Administration announced that the drugs ranitidine and nizatidine, which are used for digestive disorders, contain carcinogens. In this study, we investigated the effects of ranitidine and nizatidine on the development of GI cancer. Materials and methods: In this study, using National Health Insurance Service-National Sample Cohort (NHIS-NSC) version 2.5 (updated from 2002 to 2019), subjects who developed GI cancer were enrolled in the case group, and those who were at risk of, but did not develop, cancer were enrolled in the control group. Thereafter, risk-set matching was performed (1:3 ratio) by sex and age at the time of diagnosis of cancer in the case group. Through this procedure, 22,931 cases and 68,793 controls were identified. The associations of ranitidine and/or nizatidine with GI cancer were confirmed by adjusted odds ratios (aORs) and 95% confidence intervals (CIs) calculated through conditional logistic regression analysis. Results: The aORs of ranitidine and/or nizatidine users were lower than those of nonusers in all average prescription days groups (< 30 days/year: aOR [95% CI] = 0.79 [0.75-0.82]; 30-59 days/year: aOR [95% CI] = 0.66 [0.59-0.73]; 60-89 days/year: aOR [95% CI] = 0.69 [0.59-0.81]; ≥ 90 days/year: aOR [95% CI] = 0.69 [0.59-0.79]). Sensitivity analyses were conducted with different lag periods for the onset of GI cancer after drug administration, and these analyses yielded consistent results. Additional analyses were also performed by dividing subjects into groups based on cancer types and CCI scores, and these analyses produced the same results. Conclusion: Our study, using nationwide retrospective cohort data, did not find evidence suggesting that ranitidine and nizatidine increase the risk of GI cancer. In fact, we observed that the incidence of GI cancer was lower in individuals who used the drugs compared to nonusers. These findings suggest a potential beneficial effect of these drugs on cancer risk, likely attributed to their ability to improve digestive function.

The effects of hospice care on healthcare expenditure among cancer patients.

PURPOSE: It is necessary to estimate the hospice usage and hospice-related cost for entire cancer patients using nationwide cohort data to establish a suitable ethical and cultural infrastructure. This study aims to show the effects of hospital hospice care on healthcare expenditure among South Korean cancer patients. METHODS: This study is a retrospective cohort study using customized health information data provided by the National Health Insurance Service. Individuals who were diagnosed with stomach, colorectal, or lung cancer between 2003 and 2012 were defined as new cancer patients, which included 7,176 subjects. Patients who died under hospital-based hospice care during the follow-up period from January 2016 to December 2018 comprised the treatment group. Healthcare expenditure was the dependent variable. Generalized estimating equations was used. RESULTS: Among the subjects, 2,219 (30.9%) had used hospice care at an average total cost of 948,771 (± 3,417,384) won. Individuals who had used hospice care had a lower odds ratio (EXP(ß)) of healthcare expenditure than those who did not (Total cost: EXP(ß) = 0.27, 95% confidence intervals (CI) = 0.25-0.30; Hospitalization cost: EXP(ß) = 0.32, 95% CI = 0.29-0.35; Outpatient cost: EXP(ß) = 0.02, 95% CI = 0.02-0.02). CONCLUSION: Healthcare expenditure was reduced among those cancer patients in South Korea who used hospice care compared with among those who did not. This emphasizes the importance of using hospice care and encourages those hesitant to use hospice care. The results provide useful insights into both official policy and the existing practices of healthcare systems.

Association of polypharmacy with all-cause mortality and adverse events among elderly colorectal cancer survivors.

BACKGROUND: The risk of inappropriate drug exposure in elderly colorectal cancer (CRC) survivors after the initial cancer treatment has not been well studied. This study investigated the association of polypharmacy (PP) with overall survival, hospitalization, and emergency room (ER) visits among older CRC survivors. METHODS: A retrospective cohort study was conducted using the Korean National Health Insurance claims data follow-up from 2002 to 2017. Participants comprised those aged ≥65 years who were hospitalized with a diagnosis of CRC received cancer treatment and survived at least 2 years from the initial CRC diagnosis between 2003 and 2012. PP was defined based on the number of individual drugs during the third year, after 2 years of survival since the initial cancer treatment. PP was categorized as follows: non-PP (zero to four prescribed drugs); PP (five to nine drugs), and excessive PP (≥10 drugs). Main outcomes are all-cause mortality, hospitalization, and ER visits. RESULTS: Of the 55,228 participants, 44.5% died, 83.1% were hospitalized, and 46.1% visited the ER. The PP and excess PP groups showed increased risk of all-cause mortality, hospitalization, and ER visit compared with the low PP group, and was highly associated among groups including patients aged 65 to 74 years and those in low-level frailty groups. CONCLUSIONS: These risks can be minimized by increasing awareness and enhancing behaviors among health care professionals, especially clinician and pharmacists, to be aware of potential drug interactions, review, and ongoing monitoring. PLAIN LANGUAGE SUMMARY: The risk of inappropriate drug exposure in older colorectal cancer (CRC) survivors after the initial cancer treatment has not been well studied. Polypharmacy was associated with adverse outcomes, including all-cause mortality, hospitalization, and emergency room visits among older CRC survivors and it was particularly associated with those who were 65 to 75 years and those with low risk of frailty. When prescribing drugs, physicians should be mindful of finding a balance between adequate treatment of diseases and avoiding adverse drug effects in survivors of CRC.

Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras-transformed human breast epithelial cells.

Efforts have been made to develop a chemoprevention strategy that selectively triggers apoptosis in malignant cancer cells. Previous studies showed that capsaicin, the major pungent ingredient of red pepper, had differential effect between normal and transformed cells. As an approach to unveil the molecular mechanism by which capsaicin selectively induces apoptosis in transformed cells, we investigated the effect of capsaicin in nontransformed and ras-transformed cells of a common origin: parental (MCF10A) and H-ras-transformed (H-ras MCF10A) human breast epithelial cells. Here, we show that capsaicin selectively induces apoptosis in H-ras-transformed cells but not in their normal cell counterparts. The capsaicin-induced apoptosis, which is dependent on ras transformation, involves the activity of DEVDase (caspase-3 like). In H-ras MCF10A cells, capsaicin treatment markedly activated c-Jun N-terminal protein kinase (JNK)-1 and p38 matigen-activated protein kinase (MAPK) while it deactivated extracellular signal-regulated protein kinases (ERKs). The use of kinase inhibitors and overexpression of dominant-negative forms of MAPKs demonstrated a role of JNK-1 and p38, but not that of ERKs, in apoptosis induced by capsaicin in H-ras-transformed MCF10A cells. Based on the present study, we propose that capsaicin selectively induces apoptosis through modulation of ras-downstream signaling molecules in ras-activated MCF10A cells. Taken in conjunction with the fact that uncontrolled ras activation is probably the most common genetic defect in human cancer cells, our finding may be critical to the chemopreventive potential of capsaicin and for developing a strategy to induce tumor cell-specific apoptosis.