Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Skeletal muscle metastasis of gastric cancer is extremely rare and is associated with various symptoms. Here, we report on a 60-year-old woman with right hip pain after excessive walking. Two years earlier, the patient had been treated for advanced gastric cancer (surgery, adjuvant chemotherapy). Upon magnetic resonance imaging, diffuse muscle swelling and high signal intensity were observed in T2-weighted images of the right hip muscle. However, the FDG uptake in the right gluteal muscles was not obviously increased. Pathological examination of muscle biopsy revealed metastatic adenocarcinoma of stomach origin. The patient was treated with chemotherapy, and the swelling and pain in the right hip are progressively improving.

Skeletal muscle metastasis of gastric cancer is extremely rare and is associated with various symptoms. Here, we report on a 60-year-old woman with right hip pain after excessive walking. Two years earlier, the patient had been treated for advanced gastric cancer (surgery, adjuvant chemotherapy). Upon magnetic resonance imaging, diffuse muscle swelling and high signal intensity were observed in T2-weighted images of the right hip muscle. However, the FDG uptake in the right gluteal muscles was not obviously increased. Pathological examination of muscle biopsy revealed metastatic adenocarcinoma of stomach origin. The patient was treated with chemotherapy, and the swelling and pain in the right hip are progressively improving.

BACKGROUND: The objective of this study was to establish the efficacy and safety of procalcitonin (PCT)-guided antibiotic discontinuation in critically ill patients with sepsis in a country with a high prevalence of antimicrobial resistance and a national health insurance system. METHODS: In a multi-center randomized controlled trial, patients were randomly assigned to a PCT group (stopping antibiotics based on a predefined cut-off range of PCT) or a control group. The primary end-point was antibiotic duration. We also performed a cost-minimization analysis of PCT-guided antibiotic discontinuation. RESULTS: The two groups (23 in the PCT group and 29 in the control group) had similar demographic and clinical characteristics except for need for renal replacement therapy on ICU admission (46% vs. 14%; P = 0.010). In the per-protocol analysis, the median duration of antibiotic treatment for sepsis was 4 days shorter in the PCT group than the control group (8 days; interquartile range [IQR], 6–10 days vs. 14 days; IQR, 12–21 days; P = 0.001). However, main secondary outcomes, such as clinical cure, 28-day mortality, hospital mortality, and ICU and hospital stays were not different between the two groups. In cost evaluation, PCT-guided therapy decreased antibiotic costs by USD 30 (USD 241 in the PCT group vs. USD 270 in the control group). The results of the intention-to-treat analysis were similar to those obtained for the per-protocol analysis. CONCLUSION: PCT-guided antibiotic discontinuation in critically ill patients with sepsis could reduce the duration of antibiotic use and its costs with no apparent adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02202941
Anti-Bacterial Agents ; Biomarkers ; Calcitonin ; Costs and Cost Analysis ; Critical Illness ; Hospital Mortality ; Humans ; Intensive Care Units ; Length of Stay ; Mortality ; National Health Programs ; Prevalence ; Renal Replacement Therapy ; Sepsis

Despite the increasing use of the rectal balloon in prostate cancer radiotherapy, many issues still remain to be verified objectively including its positional reproducibility and relevance to treatment morbidity. We have developed a custom rectal balloon that has a scale indicating the depth of insertion and dilates symmetrically ensuring positional reproducibility. Fifty patients with prostate cancer treated by definitive 3D-conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) with rectal balloon were analyzed. Each of first five patients undergone computed tomography (CT) three times with a rectal balloon. The positional reproducibility was tested by Intraclass Correlation Coefficient (ICC) from the CT-to-CT fusion images. Planning variables and clinical acute toxicities were compared between when or not applying balloon. An ICC of greater than 0.9 in all directions revealed an excellent reproducibility of the balloon. Rectal balloon improved considerably the mean dose and V(45Gy)-V(65Gy) in plan comparison, and especially in 3D-CRT the rectal volume exposed to more than 60 Gy dropped from 41.3% to 19.5%. Clinically, the balloon lowered acute toxicity, which was lowest when both the balloon and IMRT were applied simultaneously. The rectal balloon carries excellent reproducibility and reduces acute toxicity in 3D-CRT and IMRT for prostate cancer.
Balloon Dilatation/*methods ; Dose-Response Relationship, Radiation ; Humans ; Male ; Neoplasm Staging ; Prostatic Neoplasms/*radiotherapy ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated ; *Rectum ; Tomography, X-Ray Computed ; Treatment Outcome

PURPOSE: To investigate the care patterns for radiation therapy and to determine inter-hospital differences for patients with laryngeal carcinoma in Korea. MATERIALS AND METHODS: A total of 237 cases of laryngeal carcinoma (glottis, 144; supraglottis, 93) assembled from 23 hospitals, who underwent irradiation in the year of 1998 and 1999, were retrospectively analyzed to investigate inter-hospital differences with respect to radiotherapy treatment. We grouped the 23 hospitals based on the number of new patients annually irradiated in 1998; and designated them as group A (> or =900 patients), group B (> or =400 patients and <900 patients), and group C (<400 patients). RESULTS: The median age of the 237 patients was 62 years (range, 25 to 88 years), of which 216 were male and 21 were female. The clinical stages were distributed as follows: for glottis cancer, I; 61.8%, II; 21.5%, III; 4.2%, IVa; 11.1%, IVb; 1.4%, and in supraglottic cancer, I; 4.3%, II; 19.4%, III; 28.0%, IVa; 43.0%, IVb; 5.4%, respectively. Some differences were observed among the 3 groups with respect to the dose calculation method, radiation energy, field arrangement, and use of an immobilization device. No significant difference among 3 hospital groups was observed with respect to treatment modality, irradiation volume, and median total dose delivered to the primary site. CONCLUSION: This study revealed that radiotherapy process and patterns of care are relatively uniform in laryngeal cancer patients in Korean hospitals, and we hope this nationwide data can be used as a basis for the standardization of radiotherapy for the treatment of laryngeal cancer.
Female ; Glottis ; Humans ; Immobilization ; Korea ; Laryngeal Neoplasms ; Male ; Retrospective Studies

BACKGROUND: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. MATERIALS AND METHODS: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of 23.4~59.4 Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-ICBT) was also performed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of 14.4~43.2 Gy (Median 36.0) of EBRT in 495 patients, while in the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor (alpha/beta=10) and late-responding tissues (alpha/beta=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED Gy3 and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED Gy3 and rectal complications and between V-BED Gy3 and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED Gy10, and the treatment duration. RESULTS: The overall complication rate for RTOG Grades 1~4 toxicities was 33.1%. The 5-year actuarial pelvic control rate for all 743 patients was 83%. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 Gy10 (median 93.0) for tumors and from 93.6 to 187.3 Gy3 (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED Gy3) and bladder point BED (V-BED Gy3) were 118.7 Gy3 (range 48.8~265.2) and 126.1 Gy3 (range: 54.9~267.5), respectively. MD-BED Gy3 showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED Gy3 had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED Gy3. B-BED Gy3 also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. CONCLUSION: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences in tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.
Appointments and Schedules* ; Brachytherapy ; Cohort Studies ; Dose Fractionation* ; Female ; Humans ; Individuality ; Logistic Models ; Pelvis ; Radiotherapy* ; Recurrence ; Urinary Bladder ; Uterine Cervical Neoplasms*

BACKGROUND: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. MATERIALS AND METHODS: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of 23.4~59.4 Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-ICBT) was also performed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of 14.4~43.2 Gy (Median 36.0) of EBRT in 495 patients, while in the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor (alpha/beta=10) and late-responding tissues (alpha/beta=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED Gy3 and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED Gy3 and rectal complications and between V-BED Gy3 and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED Gy10, and the treatment duration. RESULTS: The overall complication rate for RTOG Grades 1~4 toxicities was 33.1%. The 5-year actuarial pelvic control rate for all 743 patients was 83%. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 Gy10 (median 93.0) for tumors and from 93.6 to 187.3 Gy3 (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED Gy3) and bladder point BED (V-BED Gy3) were 118.7 Gy3 (range 48.8~265.2) and 126.1 Gy3 (range: 54.9~267.5), respectively. MD-BED Gy3 showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED Gy3 had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED Gy3. B-BED Gy3 also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. CONCLUSION: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences in tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.
Appointments and Schedules* ; Brachytherapy ; Cohort Studies ; Dose Fractionation* ; Female ; Humans ; Individuality ; Logistic Models ; Pelvis ; Radiotherapy* ; Recurrence ; Urinary Bladder ; Uterine Cervical Neoplasms*

PURPOSE: Firstly, to analyze factors in terms of radiation treatment that might potentially cause subfrontal relapse in two patients who had been treated by craniospinal irradiation (CSI) for medulloblastoma. Secondly, to explore an effective salvage treatment for these relapses. MATERIALS AND METHODS: Two patients who had high-risk disease (T3bM1, T3bM3) were treated with combined chemoradiotherapy. CT-simulation based radiation-treatment planning (RTP) was performed. One patient who experienced relapse at 16 months after CSI was treated with salvage surgery followed by a 30.6 Gy IMRT (intensity modulated radiotherapy). The other patient whose tumor relapsed at 12 months after CSI was treated by surgery alone for the recurrence. To investigate factors that might potentially cause subfrontal relapse, we evaluated thoroughly the charts and treatment planning process including portal films, and tried to find out a method to give help for placing blocks appropriately between subfrotal-cribrifrom plate region and both eyes. To salvage subfrontal relapse in a patient, re-irradiation was planned after subtotal tumor removal. We have decided to treat this patient with IMRT because of the proximity of critical normal tissues and large burden of re-irradiation. With seven beam directions, the prescribed mean dose to PTV was 30.6 Gy (1.8 Gy fraction) and the doses to the optic nerves and eyes were limited to 25 Gy and 10 Gy, respectively. RESULTS: Review of radiotherapy portals clearly indicated that the subfrontal-cribriform plate region was excluded from the therapy beam by eye blocks in both cases, resulting in cold spot within the target volume. When the whole brain was rendered in 3-D after organ drawing in each slice, it was easier to judge appropriateness of the blocks in port film. IMRT planning showed excellent dose distributions (Mean doses to PTV, right and left optic nerves, right and left eyes: 31.1 Gy, 14.7 Gy, 13.9 Gy, 6.9 Gy, and 5.5 Gy, respectively. Maximum dose to PTV: 36 Gy). The patient who received IMRT is still alive with no evidence of recurrence and any neurologic complications for 1 year. CONCLUSION: To prevent recurrence of medulloblastoma in subfrontal-cribriform plate region, we need to pay close attention to the placement of eye blocks during the treatment. Once subfrontal recurrence has happened, IMRT may be a good choice for re-irradiation as a salvage treatment to maximize the differences of dose distributions between the normal tissues and target volume.
Brain ; Chemoradiotherapy ; Craniospinal Irradiation ; Humans ; Medulloblastoma* ; Optic Nerve ; Radiotherapy ; Recurrence*

PURPOSE: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received 63~70 Gy (Median 66 Gy, fraction size 1.8~2 Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. RESULTS: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were 15+/-1.65 and 11+/-0.95 months, respectively. There was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were 21+/-5.03 and 12+/-1.59 months, respectively, while for Arm 2 patients they were 14+/-0.94 and 10+/-1.63 months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; 44.7% versus 19.2%. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. CONCLUSION: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.
Arm ; Diagnosis ; Disease-Free Survival ; Edema ; Follow-Up Studies ; Glioblastoma* ; Humans ; Magnetic Resonance Imaging ; Multivariate Analysis ; Neurologic Examination ; Prospective Studies ; Radiotherapy* ; Retrospective Studies ; Survival Rate ; Tomography, X-Ray Computed ; Treatment Outcome ; Tumor Burden