Impact of a Rounding Checklist Implementation in the Trauma Intensive Care Unit on Clinical Outcomes.

We aimed to evaluate the effectiveness of an intensive care unit (ICU) round checklist, FAST HUGS BID (Feeding, Analgesia, Sedation, Thromboembolic prophylaxis, Head-of-bed elevation, Ulcer prophylaxis, Glycemic control, Spontaneous breathing trial, Bowel regimen, Indwelling catheter removal, and De-escalation of antibiotics-abbreviated as FD hereafter), in improving clinical outcomes in patients with severe trauma. We included patients admitted to our trauma ICU from 2016 to 2020 and divided them into two groups: before (before-FD, 2016-2017) and after (after-FD, 2019-2020) implementation of the checklist. We compared patient characteristics and clinical outcomes, including ICU and hospital length of stay (LOS) and in-hospital mortality. Survival analysis was performed using Kaplan-Meier curves and multivariable logistic regression models; furthermore, multiple linear regression analysis was used to identify independent factors associated with ICU and hospital LOS. Compared with the before-FD group, the after-FD group had significantly lower in-hospital mortality and complication rates, shorter ICU and hospital LOS, and reduced duration of mechanical ventilation. Moreover, implementation of the checklist was a significant independent factor in reducing ICU and hospital LOS and in-hospital mortality. Implementation of the FD checklist is associated with decreased ICU and hospital LOS and in-hospital mortality.

Social Inequities in the Survival of Liver Cancer: A Nationwide Cohort Study in Korea, 2007-2017.

BACKGROUND: To analyze the effects of socioeconomic status (type of insurance and income level) and cancer stage on the survival of patients with liver cancer in Korea. METHODS: A retrospective cohort study was constructed using data from the Healthcare Big Data Platform project in Korea between January 1, 2007, and December 31, 2017. A total of 143,511 patients in Korea diagnosed with liver cancer (International Classification of Diseases, 10th Revision [ICD-10] codes C22, C220, and C221) were followed for an average of 11 years. Of these, 110,443 died. The patient's insurance type and income level were used as indicators of socioeconomic status. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards regression model to analyze the relationship between the effects of sex, age, and cancer stage at first diagnosis (Surveillance, Epidemiology, and the End Results; SEER), type of insurance, and income level on the survival of patients with liver cancer. The interactive effects of the type of insurance, income level, and cancer stage on liver cancer death were also analyzed. RESULTS: The lowest income group (medical aid) showed a higher risk for mortality (HR (95% CI); 1.37 (1.27-1.47) for all patients, 1.44 (1.32-1.57) for men, and 1.16 (1.01-1.34) for women) compared to the highest income group (1-6) among liver cancer (ICD-10 code C22) patients. The risk of liver cancer death was also higher in the lowest income group with a distant cancer stage (SEER = 7) diagnosis than for any other group. CONCLUSION: Liver cancer patients with lower socioeconomic status and more severe cancer stages were at greater risk of death. Reducing social inequalities is needed to improve mortality rates among patients in lower social class groups who present with advanced cancer.

Trauma system establishment and outcome improvement: a retrospective national cohort study in South Korea.

BACKGROUND: Trauma is a major cause of mortality, disability, and health care costs worldwide. The establishment of a trauma system is known to solve these problems, but few studies have objectively evaluated the impact of a trauma system on outcomes. Since 2012, South Korea has established a national trauma system based on the implementation of 17 regional trauma centers nationwide and the improvement of the prehospital transfer system. This study aimed to measure the changes in performance and outcome according to the established national trauma system. MATERIAL AND METHODS: In this national cohort-based, retrospective follow-up observational study, the authors calculated the preventable trauma death rate (PTDR) by conducting a multipanel review of patients who died in 2015, 2017, and 2019. Furthermore, the authors constructed a risk-adjusted mortality prediction model of 4 767 876 patients between 2015 and 2019 using the extended-International Classification of Disease Injury Severity Scores to compare outcomes. RESULTS: The PTDR was lower in 2019 than in 2015 (15.7 vs. 30.5, P <0.001) and 2017 (15.7 vs. 19.9%, P <0.001) representing 1247 additional lives saved in 2019 compared to that in 2015. In the risk-adjusted model, total trauma mortality was highest in 2015 at 0.56%, followed by that in 2016 and 2017 (0.50%), 2018 (0.51%), and 2019 (0.48%), revealing a significant decrease in mortality over the years ( P <0.001 for trend), representing nearly 800 additional lives saved. The number of deaths for more severe patients with a probability of survival less than 0.25 significantly decreased from 81.50% in 2015 to 66.17% in 2019 ( P <0.001). CONCLUSIONS: The authors observed a significant reduction in the PTDR and risk-adjusted trauma mortality in the 5-year follow-up since 2015 when the national trauma system was established. These findings could serve as a model for low-income and middle-income countries, where trauma systems are not yet established.

Ketamine versus etomidate for rapid sequence intubation in patients with trauma: a retrospective study in a level 1 trauma center in Korea.

BACKGROUND: Ketamine and etomidate are commonly used as sedatives in rapid sequence intubation (RSI). However, there is no consensus on which agent should be favored when treating patients with trauma. This study aimed to compare the effects of ketamine and etomidate on first-pass success and outcomes of patients with trauma after RSI-facilitated emergency intubation. METHODS: We retrospectively reviewed 944 patients who underwent endotracheal intubation in a trauma bay at a Korean level 1 trauma center between January 2019 and December 2021. Outcomes were compared between the ketamine and etomidate groups after propensity score matching to balance the overall distribution between the two groups. RESULTS: In total, 620 patients were included in the analysis, of which 118 (19.9%) were administered ketamine and the remaining 502 (80.1%) were treated with etomidate. Patients in the ketamine group showed a significantly faster initial heart rate (105.0 ± 25.7 vs. 97.7 ± 23.6, p = 0.003), were more hypotensive (114.2 ± 32.8 mmHg vs. 139.3 ± 34.4 mmHg, p < 0.001), and had higher Glasgow Coma Scale (9.1 ± 4.0 vs. 8.2 ± 4.0, p = 0.031) and Injury Severity Score (32.5 ± 16.3 vs. 27.0 ± 13.3, p < 0.001) than those in the etomidate group. There were no significant differences in the first-pass success rate (90.7% vs. 90.1%, p > 0.999), final mortality (16.1% vs. 20.6, p = 0.348), length of stay in the intensive care unit (days) (8 [4, 15] (Interquartile range)), vs. 10 [4, 21], p = 0.998), ventilator days (4 [2, 10] vs. 5 [2, 13], p = 0.735), and hospital stay (days) (24.5 [10.25, 38.5] vs. 22 [8, 40], p = 0.322) in the 1:3 propensity score matching analysis. CONCLUSION: In this retrospective study of trauma resuscitation, those receiving intubation with ketamine had greater hemodynamic instability than those receiving etomidate. However, there was no significant difference in clinical outcomes between patients sedated with ketamine and those treated with etomidate.

National Follow-up Survey of Preventable Trauma Death Rate in Korea.

BACKGROUND: The preventable trauma death rate survey is a basic tool for the quality management of trauma treatment because it is a method that can intuitively evaluate the level of national trauma treatment. We conducted this study as a national biennial follow-up survey project and report the results of the review of the 2019 trauma death data in Korea. METHODS: From January 1, 2019 to December 31, 2019, of a total of 8,482 trauma deaths throughout the country, 1,692 were sampled from 279 emergency medical institutions in Korea. All cases were evaluated for preventability of death and opportunities for improvement using a multidisciplinary panel review approach. RESULTS: The preventable trauma death rate was estimated to be 15.7%. Of these, 3.1% were judged definitive preventable deaths, and 12.7% were potentially preventable deaths. The odds ratio for preventable traumatic death was 2.56 times higher in transferred patients compared to that of patients who visited the final hospital directly. The group that died 1 hour after the accident had a statistically significantly higher probability of preventable death than that of the group that died within 1 hour after the accident. CONCLUSION: The preventable trauma death rate for trauma deaths in 2019 was 15.7%, which was 4.2%p lower than that in 2017. To improve the quality of trauma treatment, the transfer of severe trauma patients to trauma centers should be more focused.

Clinical outcomes of targeted therapies in elderly patients aged ≥ 80 years with metastatic colorectal cancer.

BACKGROUND: The 5-fluorouracil-based chemotherapy combined with oxaliplatin or irinotecan is usually used in colorectal cancer (CRC). The addition of a targeted agent (TA) to this combination chemotherapy is currently the standard treatment for metastatic CRC. However, the efficacy and safety of combination chemotherapy for metastatic CRC in patients aged above 80 years has yet to be established. AIM: To assess the clinical outcomes and feasibility of combination chemotherapy using a TA in extremely elderly patients with CRC. METHODS: Eligibility criteria were: (1) Age above 80 years; (2) Metastatic colorectal cancer; (3) Palliative chemotherapy naïve; (4) Eastern Cooperative Oncology Group performance status 0-1; and (5) Adequate organ function. Patients received at least one dose of combination chemotherapy with or without TA. Response was evaluated every 8 wk. RESULTS: Of 30 patients, the median age of 15 patients treated with TA was 83.0 years and that of those without TA was 81.3 years. The median progression-free survival (PFS) and overall survival (OS) in patients treated with TA were 7.4 mo and 15.4 mo, respectively, compared with 4.4 mo and 15.6 mo, respectively, in patients treated without TA. There was no significant difference in PFS (P: 0.193) and OS (P: 0.748) between patients treated with and without TA. Common grade 3/4 hematologic toxicities were anemia (16.7%) and neutropenia (10.0%). After disease progression, the median OS of patients who were treated with and without salvage chemotherapy were 23.5 mo and 7.0 mo, respectively, suggesting significant difference in OS (P = 0.001). CONCLUSION: Combination chemotherapy with TA for metastatic CRC may be considered feasible in patients aged above 80 years, when with careful caution. Salvage chemotherapy can help improve OS in some selected of these elderly patients.

An Evaluation of the Effect of Performance Improvement and Patient Safety Program Implemented in a New Regional Trauma Center of Korea.

BACKGROUND: This study examined the impact of the performance improvement and patient safety (PIPS) program implemented in 2015 on outcomes for trauma patients in a regional trauma center established by a government-led project for a national trauma system in Korea. METHODS: The PIPS program was based on guidelines by the World Health Organization and American College of Surgeons. The corrective strategies were proceeded according to the loop closure principle: data-gathering and monitoring, identification of preventable trauma deaths (PTDs), evaluation of preventable factors, analysis of findings, and corrective action plans. We established guidelines and protocols for trauma care, conducted targeted education and peer review presentations for problematic cases, and enhanced resources for improvement accordingly. A comparative analysis was performed on trauma outcomes over a four-year period (2015-2018) since implementing the PIPS program, including the number of trauma team activation and admissions, time factors related to resuscitation, ventilator duration, and the rate of PTDs. RESULTS: Human resources in the center significantly increased during the period; attending surgeons responsible for trauma resuscitation from 6 to 11 and trauma nurses from 85 to 218. Trauma admissions (from 2,166 to 2,786), trauma team activations (from 373 to 1,688), and severe cases (from 22.6 to 33.8%) significantly increased (all P < 0.001). Time to initial resuscitation and transfusion significantly decreased from 120 to 36 minutes (P < 0.001) and from 39 to 16 minutes (P < 0.001). Time to surgery for hemorrhage control and decompressive craniotomy improved from 99 to 54 minutes (P < 0.001) and 181 to 135 minutes (P = 0.042). Ventilator duration and rate of PTDs significantly decreased from 6 to 4 days (P = 0.001) and 22.2% to 8.4% (P = 0.008). CONCLUSION: Implementation of the PIPS program resulted in improvements in outcomes at a regional trauma center that has just been opened in Korea. Further establishment of the PIPS program is required for optimal care of trauma patients.

Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity.

BACKGROUND: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. METHODS: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. RESULTS: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). CONCLUSION: Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

Polymicrobial Interactions Induce Multidrug Tolerance in Staphylococcus aureus Through Energy Depletion.

Staphylococcus aureus is responsible for a high number of relapsing infections, which are often mediated by the protective nature of biofilms. Polymicrobial biofilms appear to be more tolerant to antibiotic treatment, however, the underlying mechanisms for this remain unclear. Polymicrobial biofilm and planktonic cultures formed by S. aureus and Candida albicans are 10- to 100-fold more tolerant to oxacillin, vancomycin, ciprofloxacin, delafloxacin, and rifampicin compared to monocultures of S. aureus. The possibility of C. albicans matrix components physically blocking antibiotic molecules from reaching S. aureus was ruled out as oxacillin, ciprofloxacin, delafloxacin, and rifampicin were able to diffuse through polymicrobial biofilms. Based on previous findings that S. aureus forms drug tolerant persister cells through ATP depletion, we examined nutrient deprivation by determining glucose availability, which indirectly correlates to ATP production via the tricarboxylic acid (TCA) cycle. Using an extracellular glucose assay, we confirmed that S. aureus and C. albicans polymicrobial cultures depleted available glucose faster than the respective monocultures. Supporting this finding, S. aureus exhibited decreased TCA cycle activity, specifically fumarase expression, when grown in the presence of C. albicans. In addition, S. aureus grown in polymicrobial cultures displayed 2.2-fold more cells with low membrane potential and a 13% reduction in intracellular ATP concentrations than in monocultures. Collectively, these data demonstrate that decreased metabolic activity through nutrient deprivation is a mechanism for increased antibiotic tolerance within polymicrobial cultures.

Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study.

BACKGROUND: Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. METHODS: A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan-Meier methods. RESULTS: We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5-6.0 months) and 8.5 months (95% CI 5.6-11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. CONCLUSION: Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

Feasibility of Modified FOLFOX in Elderly Patients Aged ≥80 Years with Metastatic Gastric Cancer or Colorectal Cancer.

OBJECTIVE: The aim of this study was to assess the feasibility of a modified FOLFOX regimen as first-line treatment in elderly patients with metastatic gastric cancer (GC) or colorectal cancer (CRC). METHODS: We included chemotherapy-naïve patients over 80 years old with metastatic GC or CRC in our study. From September 2008 to November 2014, 28 consecutive patients were enrolled and treated with modified FOLFOX. RESULTS: The study population consisted of an equal number of GC and CRC patients. The median age was 82.2 years in the GC group and 81.1 years in the CRC group. The total number of administered cycles was 89 (with a median of 6 per patient) in the GC group and 112 (with a median of 8 per patient) in the CRC group. Median progression-free survival (PFS) and overall survival (OS) were 5.4 and 6.6 months in the GC group and 7.3 and 8.1 months in the CRC group, respectively. There was no significant difference in PFS (p = 0.941) and OS (p = 0.238) between the GC and the CRC group. The 1-year survival rates were 35.7% with GC and 42.9% with CRC. Common grade 3/4 hematology toxicities were neutropenia (10.7%) and anemia (14.3%). Salvage chemotherapy was administered to 1 patient with GC and 7 patients with CRC. CONCLUSIONS: The modified FOLFOX regimen can be cautiously considered as a first-line treatment option in extremely elderly patients with metastatic GC or CRC.

Recurrent renal cell carcinoma manifesting as a large intrathoracic fibrotic mass: A case report.

Renal cell carcinomas (RCCs) have a strong tendency to metastasize, and the most common sites are the lungs, bones and liver. Late recurrence is another feature of the RCC, with lesions appearing ≥10 years after surgical treatment. However, fibrosis has rarely been associated with the disease. The present study reports a case of recurrent RCC that manifested as a fibrotic mass within the thorax. A 48-year-old man presented with dyspnea that had persisted for 3 days. The patient had undergone a right radical nephrectomy for stage II clear cell carcinoma of the kidney 6 years previously. The patient was a current smoker, with a smoking history of 20 pack-years. Chest radiography showed pleural effusion in the right thorax with an egg-sized mass shadow within the right upper lung (RUL) field. Computed tomography (CT) showed a main mass, 7 cm in diameter, within the RUL, with heterogeneous enhancement and multiple nodules of various sizes in the lungs, suggestive of primary lung cancer or metastatic RCC. A CT-guided percutaneous needle aspiration biopsy was obtained from the main mass, but histology revealed dense fibrous tissue without any malignant cells. Positron emission tomography-CT demonstrated an irregular hypermetabolic RUL mass, with a standardized uptake value (SUV) of 5.0, along the right pleura, and small pulmonary nodules (SUV, 2.0). Ultrasound-guided biopsy was attempted for a smaller hypermetabolic pleural nodule and the result was clear cell adenocarcinoma, consistent with the previous renal histology. The present study describes the case, along with a review of the relevant literature.

Occult gastric cancer with distant metastasis proven by random gastric biopsy.

Krukenberg tumor, a rare metastatic ovarian tumor arising from gastrointestinal adenocarcinoma mainly, tends to occur in premenopausal females. Finding the origin of a Krukenberg tumor is crucial for determining prognosis. In Eastern countries, the most common origin of Krukenberg tumor is stomach cancer, which is generally diagnosed via endoscopic biopsy to investigate an abnormal mucosal lesion. Here, we describe a case of huge adnexal mass in a 33-year-old woman who presented with abdominal distension. Two independent endoscopic examinations performed by experts in two tertiary university hospitals revealed no abnormal mucosal lesion. The patient was diagnosed with a Krukenberg tumor according to findings from random endoscopic biopsies taken from normal-looking gastric mucosa in our hospital. It is very rare to be diagnosed via a random biopsy in cases where three well-trained endoscopists had not found any mucosal lesion previously. Thus, in this case, random biopsy was helpful in finding the origin of a Krukenberg tumor.

Effects of Renal Replacement Therapy in Patients Receiving Extracorporeal Membrane Oxygenation: A Meta-Analysis.

The use of renal replacement therapy (RRT) in patients receiving extracorporeal membrane oxygenation (ECMO) is increasing, but the effect of RRT on ECMO is controversial. We performed a meta-analysis to determine whether RRT is related to higher mortality in patients receiving ECMO. We searched MEDLINE, EMBASE, the Cochrane Library, and KoreaMed and found 43 observational studies with 21,624 patients receiving ECMO and then compared inpatient mortality rates of patients receiving ECMO both with and without RRT. The risk ratio (RR) of mortality between patients receiving RRT and those not receiving RRT tended to decrease as the mortality of the group not receiving RRT increased. Among patients with RRT use rates of 30% and higher, the overall mortality rates for all patients receiving ECMO tended to decrease. We found that the increase in the RR for RRT tended to be greater the longer the initiation of RRT was delayed. We suggest that in patients receiving ECMO who have high RRT use rates, RRT may decrease mortality rates.

The efficacy of low-dose transdermal fentanyl in opioid-naïve cancer patients with moderate-to-severe pain.

BACKGROUND/AIMS: Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naïve patients with moderate-to-severe cancer pain. METHODS: This study had an open-label, prospective design, and was conducted between April 2007 and February 2009 in seven tertiary cancer hospitals; 98 patients were enrolled. TDF was started using a low-dose formulation (12.5 µg/hr), and the dose was adjusted according to the clinical situation of individual patients. Pain intensity, the TDF doses used, and adverse events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to-treat and per-protocol principles. RESULTS: Of the 98 patients enrolled, 64 (65%) completed the study. The median pain intensity decreased from 6.0 to 3.0 (p < 0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was consistent across groups separated according to gender (p < 0.001), age (p < 0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain intensity (p < 0.001). The decrease in pain intensity was significantly greater in the severe group compared with the moderate group (mean ± SD, 5.10 ± 2.48 vs. 2.48 ± 1.56; p < 0.001). TDF dose (27.8 µg/hr vs. 24.8 µg/hr, p = 0.423) and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain control were not different between the two pain-intensity groups. Patients had AEs of only mild or moderate intensity; among these, nausea (38%) was the most common, followed by vomiting (22%) and somnolence (22%). CONCLUSIONS: Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted.

Bleomycin-induced flagellate erythema: A case report and review of the literature.

Bleomycin has been used most commonly in the treatment of Hodgkin's lymphoma, certain germ cell tumors (GCT) and for the sclerosis of recurrent pleural effusions. Bleomycin toxicity predominantly affects the skin and lungs. Skin toxicity includes Raynaud's phenomenon, hyperkeratosis, nail-bed changes and palmoplantar desquamation. Flagellate erythema is an unusual rash occurring specifically during bleomycin use. In the present study, we report a case of bleomycin-induced flagellate erythema in a patient with GCT. A 42-year-old male was diagnosed with stage IIIB testicular cancer and treated with bleomycin, etoposide and cisplatin chemotherapy. After 10 days from the initiation of treatment, the patient subsequently developed a generalized pruritus and erythematous linear rash that was most prominent on the trunk, and upper and lower extremities. The patient was commenced on a short course of low-dose oral prednisolone, 20 mg daily, and antihistamine. Consequently, bleomycin was withheld from the patient's treatment regimen. The present study describes the case, along with a review of the associated literature.

Comparison between concurrent and sequential chemoradiation for non-small cell lung cancer in vitro.

Current practice guidelines recommend the combination of chemotherapy and thoracic radiation for locally advanced non-small cell lung cancer (NSCLC). Previous meta-analyses have shown that concurrent chemoradiation (CCRT) may be superior to sequential chemoradiation (SCRT). However, few previous in vitro studies have analyzed these two treatment schedules. In the current study, four lung cancer cell lines harboring wild-type epidermal growth factor receptor, comprising two squamous and two non-squamous cell lines, were used. The IC10 concentrations of three platinum-based regimens were combined with radiation treatment. Cells were irradiated at 0, 2, 4, 6 and 8 Gy using a 137Cs irradiator concurrently or sequentially. Surviving fractions (SFs) were plotted as a function of the radiation dose. In A549 cells, only the docetaxel (Doc) and carboplatin (Carbo) combination showed a significant radiosensitizing effect with CCRT treatment. For the other three cell lines, no difference was identified in the SFs between CCRT and SCRT. An in vitro method of comparing CCRT with SCRT was established using lung cancer cell lines. Overall, no significant difference was detected in the radiosensitizing effect of the two treatment schedules, with the exception of the A549 cell lines treated with Doc/Carbo.

Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients.

BACKGROUND: Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis. A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine. The present randomized, double-blinded, phase II trial compared the efficacy and safety of gemcitabine plus simvastatin (GS) with those of gemcitabine plus placebo (GP) in patients with locally advanced and metastatic pancreatic cancer. METHODS: Patients were randomly assigned to receive a 3-week regimen with GS (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus simvastatin 40 mg once daily) or GP (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus placebo). The primary end point was time to progression (TTP). RESULTS: Between December 2008 and April 2012, 114 patients were enrolled. The median TTP was not significantly different between the two arms, being 2.4 months (95 % CI 0.7-4.1 months) and 3.6 months (95 % CI 3.1-4.1 months) in the GS and GP arms, respectively (P = 0.903). The overall disease control rate was 39.7 % (95 % CI 12.2-33.8 %) and 57.1 % (95 % CI 19.8-44.2 %) in the GS and GP arms, respectively (P = 0.09). The 1-year expected survival rates were similar (27.7 and 31.7 % in the GS and GP arms, respectively; P = 0.654). Occurrence of grade 3 or 4 adverse events was similar in both arms, and no patients had rhabdomyolysis. CONCLUSIONS: Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit, although it also does not result in increased toxicity. Given the emerging role of statins in overcoming resistance to anti-EGFR treatment, further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents, such as erlotinib or cetuximab, plus gemcitabine for treating advanced pancreatic cancer.

Efficacy and feasibility of gemcitabine and carboplatin as first-line chemotherapy in elderly patients with advanced non-small cell lung cancer.

BACKGROUND: Although platinum-based chemotherapy is a standard first-line treatment in advanced non-small cell lung cancer (NSCLC), further research for the safety and efficacy of combination chemotherapy in elderly patients has been required. The purpose of this study was to evaluate the efficacy and safety of gemcitabine and carboplatin as first-line treatment in elderly patients with advanced NSCLC and to evaluate the prognostic factors. METHODS: Eligibility included: (1) age of 70 years or more, (2) histologically confirmed NSCLC, (3) chemotherapy-naïve, (4) advanced disease with stage IIIB or IV, (5) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, (6) adequate organ function. Patients received intravenous carboplatin (area under curve (AUC) = 5) on day 1 and gemcitabine (1000 mg/m2) on days 1 and 8, every 3 weeks. RESULTS: The medical records of forty patients were reviewed retrospectively. Median age was 73.9 years (range, 70-84.6), and there were 27 men (67.5%). Thirty-seven patients (92.5%) had ECOG PS 0-1. Adenocarcinoma was found in 57.5%. Median cycles were administrated with 4.5 per person (range: 1-6). Best responses were partial response in 22 (55.0%) patients and stable disease (SD) in 13 (32.5%). The median progression free survival (PFS) and overall survival (OS) were 5.9 months (95% CI: 4.5-7.3 months) and 9.6 months (95% CI: 8.2-11.0 months), respectively. Grade 4 hematologic toxicities for neutropenia (7.5%), thrombocytopenia (7.5%) and anemia (5.0%) were observed. Histology was significant prognostic factor for PFS (P = 0.024). CONCLUSION: Gemcitabine and carboplatin combination chemotherapy is an effective and manageable treatment option in elderly advanced NSCLC patients with good performance status.

Interstitial Pneumonitis after Treatment with Pemetrexed for Non-small Cell Lung Cancer.

Pemetrexed is approved as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) with cisplatin and as a single agent for second-line treatment or for patients who show no disease progression after four cycles of platinum-based doublet induction chemotherapy as maintenance therapy. Pemetrexed has a modest toxicity profile and has not traditionally been regarded as a cause of interstitial pneumonitis. Here, we report on a rare case of pemetrexed-induced pneumonitis in a patient with NSCLC.