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Although both capecitabine plus oxaliplatin (CAPOX) and S-1 are accepted as adjuvant chemotherapy following gastrectomy for gastric cancer, the better option between the two is still controversial. We conducted a retrospective nationwide cohort study using data from the National Health Insurance Service of Korea. We included patients who underwent gastrectomy for a primary diagnosis of gastric cancer between January 1, 2013, and December 31, 2018. The study compared the survival outcomes of patients who received postoperative chemotherapy based on S-1 (Arm S) vs. CAPOX (Arm C), as well as other relevant clinical variables such as comorbidity and completion of planned treatment. A total of 6602 patients were included in the analysis, with 4199 in Arm S and 2403 in Arm C. After propensity score matching, the final study population consisted of 2067 patients in each arm. Arm C showed statistically inferior 5-year overall survival (OS) and disease-free survival (DFS) rates compared to Arm S (84.0% vs. 90.0%; p < 0.0001; and 78.4% vs. 86.1%; p < 0.0001). Age (65 ≥ vs. < 65) and the incomplete planned treatment also had a significant negative effect on both OS and DFS. In the multivariable analysis, Arm C still showed worse OS (hazard ratio [HR], 1.609; 95% confidence intervals [CI], 1.339–1.934; p < 0.0001) and DFS (HR, 1.552; 95% CI 1.333–1.807; p < 0.0001) than Arm S. Both S-1 and CAPOX showed excellent efficacy, but this nationwide cohort study suggests that S-1 may be a better option in certain clinical situations.

Background: Adjuvant chemotherapy can reduce recurrence rates by eradicating microscopic metastases which may persist after curative resection. However, the optimal time interval (TI) between the surgery and chemotherapy remains controversial. Objectives: This study investigated the optimal TI between surgery and chemotherapy. Design: A population-based cohort study using a nationwide claims database. Methods: The data were obtained from the Korean National Health Insurance Service (NHIS) of Korea. We included patients who underwent gastrectomy between 2013 and 2018. To determine the optimal cutoff point of TI, a restricted cubic spline Cox regression model was established, and categorized the population into three groups based on TI: the early (⩽20 days), the late (⩾35 days), and the reference group (21–34 days), and with the reference group having the lowest mortality and recurrence. Propensity score matching was performed for each group. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: After excluding ineligible participants, 6602 patients were included. The median DFS and OS did not differ significantly between the early and reference groups (p = 0.7258 and p = 0.6056, respectively). In comparison between the late and reference groups, it was significantly lower in the late group (p = 0.0079). Five-year DFS rates were 77.6% and 81.3% in the late and reference groups, respectively. The late group showed worse OS than the reference group (p = 0.0336). Five-year OS rates were 82.1% and 85.0% in the late and reference groups, respectively. In the multivariable analysis, DFS in the late group retained inferiority [adjusted hazard ratio (aHR): 1.138, 95% confidence interval (CI): 1.003–1.292, p = 0.045]. OS showed a worse trend without significance compared to the reference group (aHR: 1.138, 95% CI: 0.984–1.317, p = 0.0805). Conclusion: Adjuvant chemotherapy after gastrectomy in patients with gastric cancer should be initiated within 5 weeks of surgery. A delay of more than 5 weeks may have a detrimental effect on the subsequent disease course. Plain language summary When is the best time to start adjuvant chemotherapy after stomach cancer surgery? After a patient undergoes surgery for stomach cancer, if it is stage 2 or 3, they will receive chemotherapy for a certain period of time to reduce the possibility of recurrence. However, physicians are not clear about when it is best to start chemotherapy after surgery. The study aimed to find out the best time interval between surgery and chemotherapy for patients with gastric cancer. We used data from a nationwide claims database in Korea and included patients who underwent gastrectomy between 2013 and 2018. The population has categorized the population into three groups based on the time interval: early (⩽ 20 days), late (⩾ 35 days), and reference group (21-34 days). We made statistical adjustments to minimize heterogeneity for each patient during the analysis. After excluding ineligible participants, 6,602 patients were included in the study. As a result of the analysis, it was observed that the possibility of recurrence was significantly increased for patients in the late group compared to the reference group. The probability of survival without recurrence for 5 years (5-year disease-free survival) was 77.6% and 81.3%, respectively. Meanwhile, there was no difference in the recurrence rate between the early group and the reference group. Since recurrence of cancer can ultimately lead to death, we examined the possibility for all-cause mortality and could observe a similar pattern of association with recurrence probability. The late group had a lower survival rate than the reference group (82.1% vs. 85.0%, respectively). However, there was no statistically significant difference between these two numbers. Even in a statistical model adjusting other clinical factors, the recurrence rate in the late group was still found to be significantly high compared to the reference group. In conclusion. the results showed that adjuvant chemotherapy after gastrectomy in patients with gastric cancer should be initiated within five weeks of surgery. A delay of more than five weeks may have a detrimental effect on the patient’s health.

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003–2007) to 39.7% (2018–2022) ( P  < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P  < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus , and extended-spectrum β-lactamase-producing Enterobacteriaceae . Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

IntroductionChronic pain is one of the most common and serious symptoms of cancer. Despite the limitations of dose titration using only one type of opioid, the effects of opioid combinations are poorly understood.Methods and analysisThis study will be conducted in accordance with the Cochrane Handbook of Systematic Reviews of Interventions 6.3. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science databases from their inception to June 2023. This review will consider all clinical trials involving patients aged ≥18 years who received opioids for chronic cancer pain. Two reviewers will independently screen and select relevant studies. The intervention will be a combination of opioids, including both strong and weak, to control cancer pain. The comparator will be set as a single opioid, with or without a placebo. For randomised controlled trials, version 2 of the Cochrane tool will be used to assess the risk of bias. For non-randomised studies, the risk of bias will be assessed using a tool for assessing the Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I). The primary outcome will be pain response; if a quantitative synthesis is not appropriate, a synthesis without a meta-analysis will be undertaken. The quality of evidence for each primary outcome will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation guidelines.Ethics and disseminationEthical approval was not required for this systematic review and meta-analysis. The findings will be disseminated through peer-reviewed (open-access) journal publications and conference presentations. Given the widespread use of opioid-based cancer pain management in clinical practice, this study is expected to generate significant interest among physicians, many of whom are likely to review and consider the findings in the context of their clinical decision-making.PROSPERO registration numberPROSPERO CRD42023427299.

Background Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. Methods We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). Results A total of 363 patients [ n  = 129 (ICI) and n  = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively ( p  = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively ( p  = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS ( p  < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. Conclusions No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. Trial registration This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).

Background Cancer cachexia (CC) is a multifactorial process characterized by progressive weight loss, muscle mass, and fat tissue wasting, which adversely affects the quality of life and survival of patients with advanced stages of cancer. CC has a complex and multifactorial pathophysiology, and there is no established standard treatment. Therefore, it is often irreversible and a single treatment modality is unlikely to suppress its progression. We are conducting a randomized trial to investigate the efficacy and safety of a multimodal intervention compared to the best supportive care for patients who received palliative chemotherapy. Methods Patients with lung or gastrointestinal cancers undergoing palliative chemotherapy are eligible. Patients are randomized into a multimodal intervention care (MIC) arm versus a conventional palliative care (CPC) arm. MIC includes ibuprofen, omega-3-fatty acid, oral nutritional supplement, weekly physical, psychiatric assessment, nutritional counseling, and complementary and alternative medicine. CPC includes basic nutritional counseling and megestrol acetate as needed (i.e., anorexia ≥ grade 2). All interventions are performed for 12 weeks per subject. The co-primary outcomes are change (kg) in total lean body mass and handgrip strength (kg) from the baseline. A total of 112 patients will be assigned to the two arms (56 in each group). Discussion The purpose of this study is to evaluate the effect of MIC in preventing or alleviating CC in patients who underwent palliative chemotherapy. As there is no established single treatment for CC, it is expected that the results of this clinical trial will provide new insights to significantly improve the quality of life of patients with cancer. Considering the complex mechanisms of cachexia, the effect of MIC rather than a single specific drug is more promising. In this study, we did not overly restrict the type of cancer or chemotherapy. Therefore, we attempted to measure the effects of complex interventions while preserving clinical situations. Thus, it is expected that the results of this study can be applied effectively to real-world practice. Trial registration This clinical trial was registered in the Clinical Research Information Service (KCT0004967), Korean Clinical Trial Registry on April 27, 2020, and ClinicalTrial.gov (NCT 04907864) on June 1, 2021.

Background Pneumatosis cystoides intestinalis (PCI) is a rare self-limiting condition characterized by air-filled cysts within intestinal walls. Diagnosis should be prudent because it can mimic pneumoperitoneum leading to unnecessary treatment such as surgical exploration. Although various drugs including anti-neoplastic agents have been suggested as etiologies, cases related to sunitinib are sparse. Because of the rarity of this unusual side effect by sunitinib, we report the case report. Case presentation A 68-year-old female with pancreatic neuroendocrine tumor who was treated with sunitinb for 4 months visited to our hospital complaining of severe diarrhea and mild abdominal discomfort. The abdominal X-ray showed subdiaphragmatic air mimicking intestinal perforation. After the meticulous evaluation including abdomino-pelvic computed tomography, the patient was diagnosed of PCI induced by sunitinib and fully recovered with conservative management. Conclusions It is important to note that PCI can develop after treatment with sunitinib because PCI has not been widely known as an adverse event caused by the agent. Furthemore, emergent surgery while sunitinib was administrated without adequate washout period can result in substantial surgical complications which could be avoided with the precise diagnosis.

Given the high incidence of metastatic esophageal squamous cell carcinoma, especially in Asia, we screened for the presence of somatic mutations using OncoMap platform with the aim of defining subsets of patients who may be potential candidate for targeted therapy. We analyzed 87 tissue specimens obtained from 80 patients who were pathologically confirmed with esophageal squamous cell carcinoma and received 5-fluoropyrimidine/platinum-based chemotherapy. OncoMap 4.0, a mass-spectrometry based assay, was used to interrogate 471 oncogenic mutations in 41 commonly mutated genes. Tumor specimens were prepared from primary cancer sites in 70 patients and from metastatic sites in 17 patients. In order to test the concordance between primary and metastatic sites from the patient for mutations, we analyzed 7 paired (primary-metastatic) specimens. All specimens were formalin-fixed paraffin embedded tissues and tumor content was >70%. In total, we have detected 20 hotspot mutations out of 80 patients screened. The most frequent mutation was PIK3CA mutation (four E545K, five H1047R and one H1047L) (N = 10, 11.5%) followed by MLH1 V384D (N = 7, 8.0%), TP53 (R306, R175H and R273C) (N = 3, 3.5%), BRAF V600E (N = 1, 1.2%), CTNNB1 D32N (N = 1, 1.2%), and EGFR P733L (N = 1, 1.2%). Distributions of somatic mutations were not different according to anatomic sites of esophageal cancer (cervical/upper, mid, lower). In addition, there was no difference in frequency of mutations between primary-metastasis paired samples. Our study led to the detection of potentially druggable mutations in esophageal SCC which may guide novel therapies in small subsets of esophageal cancer patients.

ObjectivesThis study determined attitudes of four groups—Korean patients with cancer, their family caregivers, physicians and the general Korean population—towards five critical end-of-life (EOL) interventions—active pain control, withdrawal of futile life-sustaining treatment (LST), passive euthanasia, active euthanasia and physician-assisted suicide.Design and settingWe enrolled 1001 patients with cancer and 1006 caregivers from 12 large hospitals in Korea, 1241 members of the general population and 928 physicians from each of the 12 hospitals and the Korean Medical Association. We analysed the associations of demographic factors, attitudes towards death and the important components of a ‘good death’ with critical interventions at EoL care.ResultsAll participant groups strongly favoured active pain control and withdrawal of futile LST but differed in attitudes towards the other four EoL interventions. Physicians (98.9%) favoured passive euthanasia more than the other three groups. Lower proportions of the four groups favoured active euthanasia or PAS. Multiple logistic regression showed that education (adjusted OR (aOR) 1.77, 95% CI 1.33 to 2.36), caregiver role (aOR 1.67, 95% CI 1.34 to 2.08) and considering death as the ending of life (aOR 1.66, 95% CI 1.05 to 1.61) were associated with preference for active pain control. Attitudes towards death, including belief in being remembered (aOR 2.03, 95% CI 1.48 to 2.79) and feeling ‘life was meaningful’ (aOR 2.56, 95% CI 1.58 to 4.15) were both strong correlates of withdrawal of LST with the level of monthly income (aOR 2.56, 95% CI 1.58 to 4.15). Believing ‘freedom from pain’ negatively predicted preference for passive euthanasia (aOR 0.69, 95% CI 0.55 to 0.85). In addition, ‘not being a burden to the family’ was positively related to preferences for active euthanasia (aOR 1.62, 95% CI 1.39 to 1.90) and PAS (aOR 1.61, 95% CI 1.37 to 1.89).ConclusionGroups differed in their attitudes towards the five EoL interventions, and those attitudes were significantly associated with various attitudes towards death.

Pulmonary manifestations of benign metastasizing leiomyoma (BML) usually include multiple well-defined, round, bilateral nodules. Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine tumor. A 70-year-old woman visited the clinic complaining of acute cough and dyspnea in April 2017. Chest computed tomography (CT) revealed pneumothorax and multiple pulmonary nodules. She had a history of hysterectomy for uterine leiomyoma 23 years ago. Biopsy revealed that the pulmonary masses were consistent with BML. However, the patient had two subsequent episodes of acute, recurrent respiratory distress, accompanied by massive pleural effusions and hydropneumothorax over the next two years. A chest CT performed for acute dyspnea revealed large and multiple hydropneumothoraces. The size and distribution of pulmonary masses were aggravated along with cystic changes and bilateral pleural effusions. Given this aggressive feature, additional immunohistochemical findings and gynecologic pathologist review confirmed the correct diagnosis to be LG-ESS. After initiating anti-estrogen therapy, the patient achieved a partial response, without recurrence of symptoms, for 28 months. Metastatic LG-ESS responds well to anti-hormonal therapy. If the clinical pattern of a disease is different than expected, the possibility of a correction in the diagnosis should be considered.