Although malignant bowel obstruction (MBO) often is a terminal event, systemic therapies are advocated for select patients to extend survival. This study aimed to evaluate factors associated with receipt of chemotherapy after MBO and to determine whether chemotherapy after MBO is associated with survival.

This retrospective cohort study investigated patients 65 years of age or older with metastatic gastrointestinal, gynecologic, or genitourinary cancers who were hospitalized with MBO from 2008 to 2012 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Fine and Gray models were used to identify factors associated with receipt of chemotherapy accounting for the competing risk of death. Cox models identified factors associated with overall survival.

Of the 2983 MBO patients, 39% (n = 1169) were treated with chemotherapy after MBO. No differences in receipt of chemotherapy between the surgical and medical patients were found in the univariable analysis (subdistribution hazard racologic outcome for select patients with MBO. The data from this study are critical to optimizing multimodality care for these complex patients.Hilar cholangiocarcinoma (HC) is a rare and highly aggressive biliary tract neoplasm. As such, the data driving the management of this disease generally are not based on prospective clinical trial data but rather consist of retrospective experiences and limited level 1 data. Surgical resection offers the best chance of a long-term survival, but local and distant recurrences are common. This report presents landmark articles that form the basis of preoperative, operative, and adjuvant strategies for HC.Little is known about microcirculatory dysfunction following abdominal surgeries. This study aimed to evaluate changes in microvascular reactivity (MVR) before and after major abdominal surgery, assessed by near-infrared spectroscopy in conjunction with a vascular occlusion test. This prospective observational study included 50 adult patients who underwent hepato-pancreato-biliary surgery lasting ≥ 8 h. MVR was assessed by tissue oxygen saturation (StO2) changes in the plantar region of the foot during 3 min of vascular occlusion and subsequent release under general anesthesia before and after surgery. The primary outcome was alteration in the recovery slope of StO2 (RecStO2) and recovery time (tM) between the preoperative and postoperative values. Postoperative short-term outcome was represented by the Post-operative Morbidity Survey (POMS) score on the morning of postoperative day 2. After surgery, RecStO2 was reduced (0.74% [0.58-1.06]/s vs. 0.89% [0.62-1.41]/s, P = 0.001), and tM was longer (57.0 [42.9-71.0] s vs. 41.3 [35.5-56.5] s, P  less then  0.001), compared to the preoperative values. Macrohemodynamic variables such as cardiac index, arterial pressure, and stroke volume during postoperative measurement did not differ with or without relative MVR decline. In addition, the POMS score was not associated with postoperative alterations in microcirculatory responsiveness. MVR in the plantar region of the foot was reduced after major hepato-pancreato-biliary surgery regardless of macrocirculatory adequacy. Impaired MVR was not associated with short-term outcomes as long as macrocirculatory indices were well maintained. https://www.selleckchem.com/ The impact of relative microcirculatory changes, especially combined with inadequate macrocirculation, on postoperative complications remains to be elucidated.Clinical Trial Registrations UMIN-CTR trial ID 000033461.Selection of suitable promoters is crucial for the efficient expression of exogenous genes in transgenic animals. Although one of the most effective promoters, the β-actin promoter, has been widely studied in fish species, it still remains unknown in the economical important African catfish (Clarias gariepinus). In this study, the β-actin promoter of African catfish (cgβ-actinP) was cloned and characterized. In addition, recombinant plasmid pcgβ-actinP-EGFP with enhanced green fluorescent protein (GFP) gene as the reporter gene was constructed to verify the transcriptional activity. We obtained a cgβ-actinP fragment length of 1405 bp, consisting 104 bp of the 5' proximal promoter, 96 bp of the first exon, and 1205 bp of the first intron. Similar to those of other fish species, cgβ-actinP contains three key transcription regulatory elements (CAAT box, CArG motif, and TATA box). GFP-specific fluorescent signals were detected in chicken embryonic fibroblasts cells (DF-1 cells) transfected with pcgβ-actinP-EGFP, which was approximately 1.11 times of the positive control. In addition, GFP was effectively expressed in zebrafish larvae microinjected with linearized cgβ-actinP-EGFP, with expression rate reaching approximately 49.84%. Our data indicate that cgβ-actinP could be a potential candidate promoter in the practice of constructing "all fish" transgenic fish.Introduction The combination of an anti-angiogenic agent with cytotoxic chemotherapy is a standard treatment strategy for metastatic colorectal cancer. CKD-516 is an oral vascular disrupting agent that was preliminarily shown to be safe and efficacious as a monotherapy in refractory solid cancers. We evaluated the recommended phase 2 dose, safety, and preliminary efficacy of CKD-516 in combination with irinotecan in treatment-refractory metastatic colorectal cancer. Methods This phase 1 dose-escalation and dose-expansion study included patients with treatment-refractory metastatic colorectal cancer. CKD-516 tablets were administered for five consecutive days followed by two days off in combination with intravenous irinotecan (120 mg/m2) administered on day one of each treatment cycle every two weeks. A traditional 3 + 3 dose-escalation design was used. Results In total, 16 and 23 patients were enrolled in the dose-escalation and dose-expansion cohorts, respectively. The most common adverse events included diarrhea (79%), nausea (74%), vomiting (67%), and neutropenia (62%). No dose-limiting toxicity occurred, and the recommended phase 2 dose was determined at CKD-516/irinotecan doses of 11/120 mg/m2. No cases of cardiac ischemia, cardiac dysfunction, or thromboembolism were reported. Among the 34 patients with available tumor response assessments, one patient achieved partial response (3%) and 26 patients achieved stable disease (76%). The median progression-free survival and overall survival were 4.1 and 11.6 months, respectively. Conclusion This phase 1 study showed that the combination of oral CKD-516 and irinotecan is safe and tolerable in metastatic, treatment-refractory colorectal patients and showed favorable efficacy outcomes. Further studies to confirm these preliminary findings are warranted. Trial registration number NCT03076957 (Registered at March 10, 2017).
Although malignant bowel obstruction (MBO) often is a terminal event, systemic therapies are advocated for select patients to extend survival. This study aimed to evaluate factors associated with receipt of chemotherapy after MBO and to determine whether chemotherapy after MBO is associated with survival. This retrospective cohort study investigated patients 65 years of age or older with metastatic gastrointestinal, gynecologic, or genitourinary cancers who were hospitalized with MBO from 2008 to 2012 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Fine and Gray models were used to identify factors associated with receipt of chemotherapy accounting for the competing risk of death. Cox models identified factors associated with overall survival. Of the 2983 MBO patients, 39% (n = 1169) were treated with chemotherapy after MBO. No differences in receipt of chemotherapy between the surgical and medical patients were found in the univariable analysis (subdistribution hazard racologic outcome for select patients with MBO. The data from this study are critical to optimizing multimodality care for these complex patients.Hilar cholangiocarcinoma (HC) is a rare and highly aggressive biliary tract neoplasm. As such, the data driving the management of this disease generally are not based on prospective clinical trial data but rather consist of retrospective experiences and limited level 1 data. Surgical resection offers the best chance of a long-term survival, but local and distant recurrences are common. This report presents landmark articles that form the basis of preoperative, operative, and adjuvant strategies for HC.Little is known about microcirculatory dysfunction following abdominal surgeries. This study aimed to evaluate changes in microvascular reactivity (MVR) before and after major abdominal surgery, assessed by near-infrared spectroscopy in conjunction with a vascular occlusion test. This prospective observational study included 50 adult patients who underwent hepato-pancreato-biliary surgery lasting ≥ 8 h. MVR was assessed by tissue oxygen saturation (StO2) changes in the plantar region of the foot during 3 min of vascular occlusion and subsequent release under general anesthesia before and after surgery. The primary outcome was alteration in the recovery slope of StO2 (RecStO2) and recovery time (tM) between the preoperative and postoperative values. Postoperative short-term outcome was represented by the Post-operative Morbidity Survey (POMS) score on the morning of postoperative day 2. After surgery, RecStO2 was reduced (0.74% [0.58-1.06]/s vs. 0.89% [0.62-1.41]/s, P = 0.001), and tM was longer (57.0 [42.9-71.0] s vs. 41.3 [35.5-56.5] s, P  less then  0.001), compared to the preoperative values. Macrohemodynamic variables such as cardiac index, arterial pressure, and stroke volume during postoperative measurement did not differ with or without relative MVR decline. In addition, the POMS score was not associated with postoperative alterations in microcirculatory responsiveness. MVR in the plantar region of the foot was reduced after major hepato-pancreato-biliary surgery regardless of macrocirculatory adequacy. Impaired MVR was not associated with short-term outcomes as long as macrocirculatory indices were well maintained. https://www.selleckchem.com/ The impact of relative microcirculatory changes, especially combined with inadequate macrocirculation, on postoperative complications remains to be elucidated.Clinical Trial Registrations UMIN-CTR trial ID 000033461.Selection of suitable promoters is crucial for the efficient expression of exogenous genes in transgenic animals. Although one of the most effective promoters, the β-actin promoter, has been widely studied in fish species, it still remains unknown in the economical important African catfish (Clarias gariepinus). In this study, the β-actin promoter of African catfish (cgβ-actinP) was cloned and characterized. In addition, recombinant plasmid pcgβ-actinP-EGFP with enhanced green fluorescent protein (GFP) gene as the reporter gene was constructed to verify the transcriptional activity. We obtained a cgβ-actinP fragment length of 1405 bp, consisting 104 bp of the 5' proximal promoter, 96 bp of the first exon, and 1205 bp of the first intron. Similar to those of other fish species, cgβ-actinP contains three key transcription regulatory elements (CAAT box, CArG motif, and TATA box). GFP-specific fluorescent signals were detected in chicken embryonic fibroblasts cells (DF-1 cells) transfected with pcgβ-actinP-EGFP, which was approximately 1.11 times of the positive control. In addition, GFP was effectively expressed in zebrafish larvae microinjected with linearized cgβ-actinP-EGFP, with expression rate reaching approximately 49.84%. Our data indicate that cgβ-actinP could be a potential candidate promoter in the practice of constructing "all fish" transgenic fish.Introduction The combination of an anti-angiogenic agent with cytotoxic chemotherapy is a standard treatment strategy for metastatic colorectal cancer. CKD-516 is an oral vascular disrupting agent that was preliminarily shown to be safe and efficacious as a monotherapy in refractory solid cancers. We evaluated the recommended phase 2 dose, safety, and preliminary efficacy of CKD-516 in combination with irinotecan in treatment-refractory metastatic colorectal cancer. Methods This phase 1 dose-escalation and dose-expansion study included patients with treatment-refractory metastatic colorectal cancer. CKD-516 tablets were administered for five consecutive days followed by two days off in combination with intravenous irinotecan (120 mg/m2) administered on day one of each treatment cycle every two weeks. A traditional 3 + 3 dose-escalation design was used. Results In total, 16 and 23 patients were enrolled in the dose-escalation and dose-expansion cohorts, respectively. The most common adverse events included diarrhea (79%), nausea (74%), vomiting (67%), and neutropenia (62%). No dose-limiting toxicity occurred, and the recommended phase 2 dose was determined at CKD-516/irinotecan doses of 11/120 mg/m2. No cases of cardiac ischemia, cardiac dysfunction, or thromboembolism were reported. Among the 34 patients with available tumor response assessments, one patient achieved partial response (3%) and 26 patients achieved stable disease (76%). The median progression-free survival and overall survival were 4.1 and 11.6 months, respectively. Conclusion This phase 1 study showed that the combination of oral CKD-516 and irinotecan is safe and tolerable in metastatic, treatment-refractory colorectal patients and showed favorable efficacy outcomes. Further studies to confirm these preliminary findings are warranted. Trial registration number NCT03076957 (Registered at March 10, 2017).
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