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Purpose@#To analyze trends in corneal transplantation surgery and determine the number of domestic and imported corneal grafts used in South Korea.Method: The total number of keratoplasties and number of each individual surgical procedure conducted in 2010 and 2020 were identified using Health Insurance Review and Assessment Service data. The number of keratoplasties using domestic corneas in 2010 and 2020 was determined from the annual report of the Korean Network for Organ Sharing (KONOS). The number of keratoplasties using imported corneas was calculated by subtracting the number of keratoplasties using domestic corneas from the total number of keratoplasties. @*Results@#In 2010, 802 keratoplasties were performed in Korea, of which 299 (37.3%) used imported corneas; 715 (89.2%) were penetrating keratoplasties and 87 (10.8%) were anterior lamellar keratoplasties. In 2020, 911 keratoplasties were done in Korea and 564 (61.9%) used imported corneas; 541 (59.4%) were penetrating keratoplasties, 60 (6.6%) were anterior lamellar keratoplasties, and 310 (34.0%) were endothelial keratoplasties. From 2010 to 2020, the number of penetrating keratoplasties in Korea decreased, while the numbers of endothelial keratoplasties and keratoplasties using imported corneas increased. @*Conclusions@#There was a 30% decrease in the number of penetrating keratoplasties from 2010 to 2020, and a 30% increase in the numbers of endothelial keratoplasties and keratoplasties using imported corneas. The proportions of endothelial keratoplasties and imported corneas have increased steadily in Korea over the last 10 years.
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Background@#The prognostic nutritional index (PNI) reflects systemic inflammation and nutritional status. This study aimed to evaluate the effect of preoperative PNI on postoperative cancer-specific survival in patients with endometrial cancer (EC). @*Methods@#Demographic, laboratory, and clinical data were retrospectively collected from 894 patients who underwent surgical resection of EC. Preoperative PNIs were determined from the serum albumin concentration and total lymphocyte count, which were measured within 1 month before surgery. Patients were classified into high PNI (n = 619) and low PNI (n = 275) groups according to the preoperative PNI cut-off value of 50.6. The stabilized inverse probability of treatment weighting (IPTW) method was used to reduce bias: a weighting cohort divided into high PNI (n = 615.4) and low PNI (n = 272.3) groups. The primary outcome measure was postoperative cancer-specific survival. @*Results@#The postoperative cancer-specific survival rate was higher in the high PNI group than the low PNI group in the unadjusted cohort (93.1% vs. 81.5%; proportion difference [95% confidence interval; 95% CI], 11.6% [6.6–16.6%]; P < 0.001) and in the IPTW- adjusted cohort (91.4% vs. 86.0%; 5.4% [0.8–10.2%]; P = 0.021). In the multivariate Cox proportional hazard regression model in the IPTW-adjusted cohort, high preoperative PNI (hazard ratio [95% CI], 0.60 [0.38–0.96]; P = 0.032) was an independent determinant of postoperative cancer-specific mortality. The multivariate-adjusted restricted cubic spline curve for the Cox regression model showed a significant negative association between preoperative PNI and postoperative cancer-specific mortality (P < 0.001). @*Conclusion@#High preoperative PNI was associated with improved postoperative cancerspecific survival in patients undergoing surgery for EC.
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Purpose@#Gastrointestinal (GI) endoscopy is an important tool for diagnosing and treating GI diseases in children. This study aimed to analyze the current GI endoscopy practice patterns among South Korean pediatric endoscopists. @*Methods@#Twelve members of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition developed a questionnaire. The questionnaire was emailed to pediatric gastroenterologists attending general and tertiary hospitals in South Korea. @*Results@#The response rate was 86.7% (52/60), and 49 of the respondents (94.2%) were currently performing endoscopy. All respondents were performing esophagogastroduodenoscopy, and 43 (87.8%) were performing colonoscopy. Relatively rare procedures for children, such as double-balloon enteroscopy (DBE) (4.1%), endoscopic retrograde cholangiopancreatography (ERCP) (2.0%), and endoscopic ultrasound (EUS) (2.0%), were only performed by pediatric gastroenterologists at very few centers, but were performed by adult endoscopists in most of the centers; of all the respondents, 83.7% (41/49) performed emergency endoscopy. In most centers, the majority of the endoscopies were performed under sedation, with midazolam (100.0%) and ketamine (67.3%) as the most frequently used sedatives. @*Conclusion@#While most pediatric GI endoscopists perform common GI endoscopic procedures, rare procedures, such as DBE, ERCP, and EUS, are only performed by pediatric gastroenterologists at very few centers, and by adult GI endoscopists at most of the centers. For such rare procedures, close communication and cooperation with adult GI endoscopists are required.
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Background@#Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging.Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson’s disease (PD). @*Methods@#We investigated 97 de novo PD patients and 27 DIP patients using OCT and [ 18 F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specificon-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. @*Results@#No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all Pvalues > 0.090). The mean SNBRAI was significantly higher in PD than in DIP (P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). @*Conclusion@#Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.
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Background@#The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population. @*Methods@#Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores. @*Results@#According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all). @*Conclusion@#A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.
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Purpose@#This study aimed to investigate the impact of BRCA1/2 mutational status on survival outcomes in patients with platinum-sensitive relapsed (PSR) epithelial ovarian cancer (EOC). @*Materials and Methods@#We retrospectively identified patients who received secondary treatment for PSR EOC at our institution between January 2007 and June 2021 and who underwent BRCA1/2 gene testing by either germline or somatic methods. The association between BRCA1/2 mutational status and survival outcomes was evaluated. Both secondary cytoreductive surgery (CRS) and maintenance therapy were stratified considering real-world clinical practice. @*Results@#Of 262 patients, 91 (34.7%) and 171 (65.3%) were assigned to BRCA1/2 mutation and wild-type groups, respectively. The two groups had similar proportions of patients undergoing secondary CRS (26.4% vs. 32.7%, p=0.286) and maintenance therapy (54.9% vs. 46.2%, p=0.178). Overall, no differences in progression-free survival (PFS; median, 19.7 vs. 15.1 months, p=0.120) and overall survival (OS; p=0.400) were observed between the two groups. In multivariate analyses, BRCA1/2 mutational status was not associated with PFS (adjusted hazard ratio, 0.816; 95% confidence interval, 0.596 to 1.119; p=0.207). BRCA1/2 mutational status did not affect PFS among patients who underwent secondary CRS (n=80) and among those who did not (n=182) (p=0.074 and p=0.222, respectively). PFS did not differ in the BRCA1/2 mutational status among the patients who received bevacizumab maintenance (n=90, p=0.992). @*Conclusion@#In this real-world evidence study, BRCA1/2 mutational status itself was not associated with PFS and OS in PSR EOC, which was consistent with whether secondary CRS or not and with bevacizumab maintenance.
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Purpose@#This study aimed to compare treatment outcomes and toxicity profile between imaged-guided brachytherapy (IGBT) versus conventional brachytherapy (CBT) performed by the same practitioner during the same time period. @*Materials and Methods@#Medical records of 104 eligible patients who underwent brachytherapy for locally advanced cervical cancer were retrospectively reviewed. Fifty patients (48.1%) underwent IGBT, and 54 (51.9%) patients underwent CBT. All patients underwent concurrent chemoradiation with cisplatin. High-dose-rate intracavitary brachytherapy with dose prescription of 25-30 Gy in 4-6 fractions was performed for all patients. Late lower gastrointestinal (GI) and urinary toxicities occurred more than 3 months after the end of brachytherapy were included for comparative and dosimetric analyses. @*Results@#The median follow-up period was 18.33 months (range, 3.25 to 38.43 months). There were no differences in oncologic outcomes between the two groups. The IGBT group had lower rate of actuarial grade ≥ 3 toxicity than the CBT group (2-year, 4.5% vs. 25.7%; p=0.030). Cumulative equieffective D2cc of sigmoid colon was significantly correlated with grade ≥ 2 lower GI toxicity (p=0.033), while equieffective D2cc of rectum (p=0.055) and bladder (p=0.069) showed marginal significance with corresponding grade ≥ 2 toxicities in the IGBT group. Half of grade ≥ 3 lower GI toxicities impacted GI tract above the rectum. Optimal thresholds of cumulative D2cc of sigmoid colon and rectum were 69.7 Gy and 70.8 Gy, respectively, for grade ≥ 2 lower GI toxicity. @*Conclusion@#IGBT showed superior toxicity profile to CBT. Evaluating the dose to the GI tract above rectum by IGBT might prevent some toxicities.
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Recurrent colonic perforation in patients already having colostomy is extremely rare and only a few cases had been reported. Herein, we report 2 cases of recurrent colonic perforation at the proximal part of the colostomy in geriatric patients resulting from different causes, which might be caused by stercoral perforation and recurrent colonic ischemia, respectively. Based on our experience, surgeons should consider correcting chronic constipation even in patients who already have a colostomy.Additionally, transverse colostomy should be considered as a surgical treatment in patients with sigmoid colostomy for recurrent perforation due to colonic ischemia.
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Background@#This study evaluated occupational exposure levels of doxorubicin in healthcare workers performing rotational intraperitoneal pressurized aerosol chemotherapy (PIPAC) procedures. @*Methods@#All samples were collected during PIPAC procedures applying doxorubicin to an experimental animal model (pigs). All procedures were applied to seven pigs, each for approximately 44 min. Surface samples (n = 51) were obtained from substances contaminating the PIPAC devices, surrounding objects, and protective equipment. Airborne samples were also collected around the operating table (n = 39). All samples were analyzed using ultra-high performance liquid chromatography-mass spectrometry. @*Results@#Among the surface samples, doxorubicin was detected in only five samples (9.8%) that were directly exposed to antineoplastic drug aerosols in the abdominal cavity originating from PIPAC devices. The telescopes showed concentrations of 0.48–5.44 ng/cm2 and the trocar showed 0.98 ng/cm2 in the region where the spraying nozzles were inserted. The syringe line connector showed a maximum concentration of 181.07 ng/cm2, following a leakage. Contamination was not detected on the surgeons' gloves or shoes. Objects surrounding the operating table, including tables, operating lights, entrance doors, and trocar holders, were found to be uncontaminated. All air samples collected at locations where healthcare workers performed procedures were found to be uncontaminated. @*Conclusions@#Most air and surface samples were uncontaminated or showed very low doxorubicin concentrations during PIPAC procedures. However, there remains a potential for leakage, in which case dermal exposure may occur. Safety protocols related to leakage accidents, selection of appropriate protective equipment, and the use of disposable devices are necessary to prevent occupational exposure.
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Purpose@#To introduce an intuitive method for measuring conjunctival microvascular blood flow velocity by imaging bulbar conjunctival microvessels using a slit-lamp biomicroscope equipped with a zoom lens and an ultra-high-speed camera. @*Methods@#After obtaining consent from 10 patients (1 male, 9 females) who visited Yeouido St. Mary’s Hospital from August 21, 2020, to June 12, 2021, the patients were examined under a slit lamp microscope equipped with an ultra-high-speed camera and zoom lens. The blood flow in the conjunctival microvessels was photographed. The captured images were analyzed with ImageJ software to measure the blood flow velocity in the conjunctival microvessels, and we investigated whether the blood flow velocity correlated with the vessel diameter and age. @*Results@#The median age of the subjects was 49.0 years. The mean conjunctival blood flow velocity in 53 microvessels was 0.786 ± 0.468 mm/s. The median conjunctival microvascular diameter was 7.06 μm (interquartile range 5.84 to 9.23 μm). The conjunctival microvascular diameter and blood flow velocity were not significantly correlated (Spearman’s p = 0.177), and the subjects’ age and conjunctival microvascular blood flow velocity were also not correlated (Spearman’s p = 0.669). @*Conclusions@#In this study, the blood flow velocity in the bulbar conjunctival microvessels could be measured easily by means of image analysis using a slit-lamp microscope equipped with an ultra-high-speed camera with a zoom lens.
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Background@#Subjects with chronic obstructive pulmonary disease (COPD) have a higher risk of ischemic heart disease (IHD) than individuals without COPD; however, longitudinal evidence is lacking. Therefore, we aimed to estimate the risk of IHD between COPD and control cohorts using a longitudinal nationwide database. @*Methods@#We used 2009–2017 data from the Korean National Health Insurance Service National Sample Cohort (NHIS-NSC). Adult participants at least 20 years of age who underwent health examinations and without a history of COPD or IHD were included (n = 540,976). Participants were followed from January 1, 2009, until death, development of IHD, or December 31, 2019, whichever came first. @*Results@#At baseline, there were 3,421 participants with incident COPD and 537,555 participants without COPD. During a median of 8.0 years (5.3–9.1 years) of follow-up, 2.51% of the participants with COPD (n = 86) and 0.77% of the participants without COPD (n = 4,128) developed IHD, with an incidence of 52.24 and 10.91 per 10,000 person-years, respectively. Participants with COPD had a higher risk of IHD (adjusted hazard ratio, 1.55;95% confidence interval, 1.25–1.93) than subjects without COPD. Demographics such as age, sex, body mass index, and personal health behaviors including smoking status and physical activity did not show significant interaction with the relationship between COPD and IHD (P for interaction > 0.05 for all). @*Conclusion@#The results indicate that COPD is associated with the development of IHD independent of demographic characteristics and health-related behaviors. Based on these results, clinicians should closely monitor the onset of IHD in subjects with COPD.
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Background@#The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known predictors of fracture. We sought to estimate the effect of the S1P concentration on fracture risk using the FRAX probability and TBS as mediators. @*Methods@#Plasma S1P concentrations, FRAX variables, and TBSs were measured in 66 postmenopausal women with fractures and 273 postmenopausal women without fractures. Associations between S1P concentration, FRAX probability, TBS, and fracture risk were analyzed using correlation, logistic regression, and mediation analyses. @*Results@#Subjects in the highest S1P concentration tertile had a higher fracture risk (odds ratio [OR], 5.09; 95% confidence interval [CI], 2.22–11.67) than those in the lowest S1P concentration tertile before adjustment. Subjects in the highest FRAX probability tertile had a higher fracture risk (OR, 14.59; 95% CI, 5.01–42.53) than those in the lowest FRAX probability tertile before adjustment. Subjects in the lowest TBS tertile had a higher fracture risk (OR, 4.76; 95% CI, 2.28–9.93) than those in the highest TBS tertile before adjustment. After adjustment for FRAX probability and TBS, the highest S1P concentration tertile was still associated with a higher fracture risk (OR, 3.13; 95% CI, 1.28–7.66). The FRAX probability and TBS accounted for 32.6% and 21.7%, respectively, of the relationship between the S1P concentration and fracture risk. @*Conclusions@#The relationship between the circulating S1P concentration and fracture risk was partly mediated by the FRAX probability, bone microarchitecture, and other factors.
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Background/Aims@#To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis. @*Methods@#This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography. @*Results@#Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors. @*Conclusions@#In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.
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Purpose@#Obesity has been known to contribute to technical difficulties in surgery. Until now, body mass index (BMI) has been used to measure obesity. However, there are reports that BMI does not always correspond to the visceral fat. Recently, bioelectrical impedance analysis (BIA) has been used for body composition analysis. This study aimed to evaluate the usefulness of the body composition index obtained using a BIA device in predicting short-term postoperative outcomes. @*Methods@#Data of patients who underwent elective major colorectal surgery using minimally invasive techniques were reviewed retrospectively. Body composition status was recorded using a commercial BIA device the day before surgery. The relationship between BMI, body composition index, and short-term postoperative outcomes, including operative time, was analyzed. @*Results@#Sixty-six patients were enrolled in this study. In the correlation analysis, positive correlation was observed between BMI and body composition index. BMI and body composition index were not associated with short-term postoperative outcomes. Percent body fat (odds ratio, 4.226; 95% confidence interval [CI], 1.064–16.780; P=0.041) was found to be a statistically significant factor of prolonged operative time in the multivariate analysis. Correlation analysis showed that body fat mass was related to prolonged operative time (correlation coefficients, 0.245; P=0.048). In the area under curve analysis, body fat mass showed a statistically significant predictive probability for prolonged operative time (body fat mass: area, 0.662; 95% CI, 0.531–0.764; P=0.024). @*Conclusion@#The body composition index can be used as a predictive marker for prolonged operative time. Further studies are needed to determine its usefulness.
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For more anatomically precise quantitation of mouse brain PET, spatial normalization (SN) of PET onto MR template and subsequent template volumes-of-interest (VOIs)-based analysis are commonly used. Although this leads to dependency on the corresponding MR and the process of SN, routine preclinical/clinical PET images cannot always afford corresponding MR and relevant VOIs. To resolve this issue, we propose a deep learning (DL)-based individual-brain-specific VOIs (i.e., cortex, hippocampus, striatum, thalamus, and cerebellum) directly generated from PET images using the inverse-spatialnormalization (iSN)-based VOI labels and deep convolutional neural network model (deep CNN). Our technique was applied to mutated amyloid precursor protein and presenilin-1 mouse model of Alzheimer’s disease. Eighteen mice underwent T2-weighted MRI and 18 F FDG PET scans before and after the administration of human immunoglobin or antibody-based treatments. To train the CNN, PET images were used as inputs and MR iSN-based target VOIs as labels. Our devised methods achieved decent performance in terms of not only VOI agreements (i.e., Dice similarity coefficient) but also the correlation of mean counts and SUVR, and CNN-based VOIs was highly accordant with ground-truth (the corresponding MR and MR template-based VOIs). Moreover, the performance metrics were comparable to that of VOI generated by MR-based deep CNN. In conclusion, we established a novel quantitative analysis method both MR-less and SN-less fashion to generate individual brain space VOIs using MR template-based VOIs for PET image quantification.
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Purpose@#To compare the degree of meibomian gland drop-out associated with Demodex infestation using non-contact meibography. @*Methods@#We performed noncontact meibography using an infrared digital camera on 24 adult subjects infested by Demodex and 40 without infestation. The right upper and lower lids were scored based on the loss of meibomian glands, and the scores of the upper and lower eyelids were summed to obtain the total meiboscore for each subject. Meiboscores were evaluated according to Demodex infestation and gender in each group. @*Results@#Sixty-four eyes of 64 people were enrolled in this study. The study subjects had an average age of 67.9 years (range, 40-79 years; men, 65.2 years; women, 69.1 years). There was a significant association between Demodex infestation and total meiboscore and upper and lower eyelid meiboscores (p = 0.000, p = 0.002, p = 0.004, respectively). There was no significant difference in the meiboscores between men and women. Age and meiboscore suggested a weak positive correlation; however, the R2 value was low, due to the concentrated age distribution of the study population. @*Conclusions@#Based on noncontact meibography, the authors concluded that the prevalence of changes in the meibomian glands was significantly related to Demodex infestation; however, there was no significant difference between men and women.
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Background/Aims@#Although mucosal healing (MH) is acknowledged as the treatment target in the treat-to-target era, there are limitations on repeated endoscopic examinations, especially in pediatric patients. We aimed to investigate whether fecal calprotectin (FC) could serve as a surrogate marker for the assessment of MH in pediatric patients with Crohn’s disease (CD) who have achieved sustained clinical remission (CR) while treated with anti-tumor necrosis factor (TNF) agents. @*Methods@#This multicenter retrospective cross-sectional study included pediatric CD patients who had sustained a CR for at least 6 months with anti-TNF agents and who simultaneously underwent ileocolonoscopy and FC tests during follow-up. MH was defined as the absence of any ulcer on ileocolonoscopy. @*Results@#A total of 131 patients were included in this study. MH was observed in 87 patients (66.7%). The FC level was significantly lower in patients with MH than in those without MH (median 49.0 mg/kg vs 599.0 mg/kg; p<0.001). According to the multivariate logistic regression analysis, FC was the only factor associated with MH (odds ratio, 0.62; 95% confidence interval [CI], 0.52 to 0.73; p<0.001). According to the receiver operating characteristic curve analysis, the optimal cutoff value for FC for the association with MH was <140 mg/kg (area under the curve 0.890, 95% CI 0.829 to 0.951, sensitivity 78.2%, specificity 88.6%, p<0.001). @*Conclusions@#FC was associated with MH in pediatric patients with CD who had achieved a sustained CR for at least 6 months with anti-TNF agents. In these patients, FC can be used to stratify patients and guide decisions regarding ileocolonoscopy in the treat-to-target era.
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Objective@#We used paclitaxel and cisplatin, known to be effective in intraperitoneal chemotherapy, in a novel prototype of rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) and evaluated the pharmacokinetics, tissue concentrations, and toxicities in a pig model. @*Methods@#We developed RIPAC, including the nozzle with the conical pendulum motion, and used 10% of intravenous doses of paclitaxel and cisplatin. We used high-performance liquid chromatography followed by tandem mass spectrometry to analyze serum and tissue concentrations. We applied a non-compartment model to study pharmacokinetics to analyze the time-dependent serum concentrations measured before RIPAC to 48 hours. We evaluated the difference in tissue concentrations between twelve peritoneal regions by the modified peritoneal cancer index. For evaluating toxicities, we observed hepatic and renal function until 4 days after RIPAC. @*Results@#Six pigs underwent RIPAC using paclitaxel (n=3) and cisplatin (n=3). The peak serum concentration (Cmax) and the area under the curve were higher for cisplatin, while the time to the peak serum concentration (Tmax) was longer for paclitaxel. Moreover, the parietal peritoneum showed higher tissue concentrations than the visceral peritoneum, and the ratio of tissue to serum concentrations using Cmax was higher for paclitaxel (172.2–6,237.9) than for cisplatin (0.1–9.3). However, there were no renal and hepatic toxicities after RIPAC with paclitaxel or cisplatin. @*Conclusion@#Delayed absorption of paclitaxel sprayed by RIPAC into the peritoneum to the bloodstream may lead to higher tissue concentrations at different regions and lower serum concentrations than cisplatin.
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Objective@#Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. @*Methods@#This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). @*Results@#Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. @*Conclusion@#This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.
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Purpose@#To identify initial abdominal computed tomography (CT) and laboratory findings prior to a diagnosis of Crohn’s disease (CD) in children. @*Materials and Methods@#In this retrospective study, patients (≤18 year-old) who were diagnosed with CD from 2004 to 2019 and had abdominal CT just prior to being diagnosed with CD were included in the CD group. Patients (≤18 years old) who were diagnosed with infectious enterocolitis from 2018 to 2019 and had undergone CT prior to being diagnosed with enterocolitis were included as a control group. We assessed the diagnostic performances of initial CT and laboratory findings for the diagnosis of CD using logistic regression and the area under the curve (AUC). @*Results@#In total, 107 patients (50 CD patients, 57 control patients) were included, without an age difference between groups (median 13 years old vs. 11 years old, p=0.119). On univariate logistic regression analysis, multisegmental bowel involvement, mesenteric vessel engorgement, higher portal vein/aorta diameter ratio, longer liver longitudinal diameter, lower hemoglobin (≤12.5 g/ dL), lower albumin (≤4 g/dL), and higher platelet (>320×103 /μL) levels were significant factors for CD. On multivariate analysis, multisegmental bowel involvement [odds ratio (OR) 111.6, 95% confidence interval (CI) 4.778–2605.925] and lower albumin levels (OR 0.9, 95% CI 0.891–0.993) were significant factors. When these two features were combined, the AUC value was 0.985 with a sensitivity of 96% and specificity of 100% for differentiating CD. @*Conclusion@#Multisegmental bowel involvement on CT and decreased albumin levels can help differentiate CD from infectious enterocolitis in children prior to a definite diagnosis of CD.