Can clinicopathologic high-risk features in T3N0 colon cancer be reliable prognostic factors?

Purpose: The purpose of this study was to assess the reliability and prognostic significance of the high-risk feature (HRF) in patients with T3N0 colon cancer. Methods: We included 1,205 patients with pT3N0 colon cancer treated with curative radical resection between 2012 and 2016. HRF was defined as lymphovascular invasion, perineural invasion, poorly/undifferentiated histology, margin involvement, and preoperative obstruction. We investigated the relationships between the number and type of HRF and recurrence-free survival (RFS) and overall survival (OS), as well as the effect of adjuvant treatment. Results: A total of 751 of the patients (62.3%) had more than 1 HRF and 515 of the patients (42.7%) underwent adjuvant treatment. Patients who had more than 2 HRFs had a significantly worse 5-year RFS and OS compared to patients who had neither HRF nor even one HRF. According to the findings of the multivariate analysis, the presence of multiple HRFs was a risk factor for a lower RFS and OS. When the quantity and type of HRF were taken into consideration in the multivariate analysis, adjuvant chemotherapy was not found to be linked with RFS or OS in patients with pT3N0 colon cancer. Conclusion: In the present study, adjuvant treatment based on the current guideline of treatment indication was unable to enhance the prognosis of patients with pT3N0 colon cancer. The role of adjuvant treatment in T3N0 colon cancer must be examined with the HRF count in mind.

Pathologic Implications of Magnetic Resonance Imaging-detected Extramural Venous Invasion of Rectal Cancer.

BACKGROUND: Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. Recent advances in magnetic resonance imaging (MRI) allow for the detection of EMVI before surgery. This study aimed to analyze the correlations between MRI-detected EMVI (MR-EMVI) and pathologic parameters in patients with rectal cancer. MATERIALS AND METHODS: This study retrospectively analyzed 721 patients who underwent radical resection for locally advanced rectal cancer between 2018 and 2019 at the Asan Medical center. All patients underwent an MRI before surgery. The lesions of patients who received neoadjuvant chemoradiation therapy (CRT) were evaluated by MRI before and after the neoadjuvant CRT. RESULTS: Of the 721 patients, 118 (16.4%) showed a positive MR-EMVI, which significantly correlated with advanced pathologic T-category and N-category, extranodal extension, poor differentiation, lymphatic invasion, venous invasion, and perineural invasion. In addition, MR-EMVI was an independent factor for predicting the pathologic nodal status (OR 3.476, 95% CI, 2.186-5.527, P < .001). Patients with a positive MR-EMVI had a sensitivity of 28.0% and specificity of 91.9% for predicting regional lymph node metastasis, whereas the MR-N category had a sensitivity of 88.7% and specificity of 30.6%. Patients whose MR-EMVI changed from positive to negative after neoadjuvant CRT had no significant differences in pathologic parameters except for lymphatic invasion with patients who were negative before and after neoadjuvant CRT. CONCLUSION: MR-EMVI correlated with aggressive pathologic features, which indicated a poor prognosis. MR-EMVI may be a complementary imaging biomarker for predicting nodal status and evaluating tumor response to neoadjuvant CRT.

Preoperative albumin-bilirubin score as a prognostic indicator in patients with stage III colon cancer.

The albumin-bilirubin (ALBI) score was created to assess the severity of liver dysfunction and to predict prognosis of hepatocellular carcinoma. Purpose of this study was to investigate the prognostic value of the ALBI score in patients with stage III colon cancer using propensity score matching (PSM) analysis. This study analyzed 510 patients with stage III colon cancer who had surgery between 2014 and 2015. The ALBI score was calculated as follows: (log10 bilirubin (µmol/L) [Formula: see text] 0.66) + (albumin (g/L) [Formula: see text] -0.0852), and the optimal cut-off value was determined using a receiver operating characteristic analysis and the Youden Index. According to the calculated cut-off value, patients were divided into two groups: Group A (ALBI ≤ - 2.54) and Group B (ALBI > - 2.54). The average ALBI score was - 2.68 (from - 3.39 to - 0.69). Group A had a significantly higher 5-year disease-free survival rate (85.5% vs 75.7%, p = 0.02), 5-year cancer-specific survival rate (93.7% vs 84.4%, p = 0.02), and 5-year overall survival rate (90.6% vs 77.4%, p = 0.01) than Group B. High ALBI scores were found to be an independent risk factor for both disease-free survival (HR 1.68, p = 0.048) and cancer-specific survival (HR 2.24, p = 0.028). The preoperative ALBI score was found to be a promising prognostic indicator for predicting recurrence and survival in patients with stage III colon cancer in this study. Because the ALBI score is simple and inexpensive to obtain, it has the potential to be a useful clinical marker for colon cancer patients.

Comparative survival risks in patients undergoing abdominoperineal resection and sphincter-saving operation for rectal cancer: a 10-year cohort analysis using propensity score matching.

PURPOSE: Abdominoperineal resection (APR) has been considered to have a higher risk of local recurrence and poorer survival outcome than sphincter-saving operation (SSO) in patients with rectal cancer. This study compared long-term oncologic outcomes and prognostic parameters in propensity score-matched patients who underwent APR and SSO. METHODS: This study analyzed 958 consecutive patients with lower rectal cancer who underwent preoperative chemoradiotherapy followed by APR or SSO between 2005 and 2015. Propensity score matching analysis was performed to adjust baseline characteristics, including clinical stage, tumor distance from the anal verge, and tumor size. RESULTS: In the entire cohort, the APR group had larger and lower tumors and showed significantly shorter 5-year disease-free survival (DFS) than the SSO group (64.5% vs. 75.8%, p = 0.01). After propensity score matching, there were no significant between-group differences in local (9.5% vs. 8.0%, p = 0.59) and systemic (27.9% vs. 23.4%, p = 0.3) recurrence rates, and 5-year DFS (67.5% vs. 69.9%, p = 0.49) and overall survival (80.8% vs. 82.9%, p = 0.65) rates. A lower number of lymph nodes retrieved was independently associated with recurrence and survival outcomes in the APR group, whereas poorly differentiated histology was an independent associated parameter in the SSO group. Advanced stage and perineural invasion were identified as independent prognostic parameters in both groups. CONCLUSIONS: This study indicated that the long-term oncologic outcomes of APR were comparable to those of SSO. Because prognostic parameters associated with oncologic outcomes differed between the respective procedures, correctable parameters could be ameliorated through complete total mesorectal excision and personalized systemic treatment.

Impact of the COVID-19 Pandemic on Surgical Treatment Patterns for Colorectal Cancer in a Tertiary Medical Facility in Korea.

Because of their reluctance to visit the hospital due to concerns about contracting coronavirus disease 2019 (COVID-19), patients with colorectal cancer have been affected by delays in care during the pandemic. This study assessed the effects of the pandemic on the clinical characteristics and surgical treatment patterns of colorectal cancer patients at a tertiary medical facility in Korea. Patients who underwent colorectal cancer surgery at our institution between March and September 2020 were analyzed. Clinicopathological and treatment characteristics were compared with those of patients who underwent surgery in 2018 and 2019. The patients who did not undergo tumor resection (4.1% vs. 1.8%, p < 0.001) and who received neoadjuvant treatment (16.7% vs. 14.7%, p = 0.039) were significantly higher during the COVID period. The minimally invasive approach was performed less during the COVID period (81.2% vs. 88%, p < 0.001). More patients in the COVID period required combined resection of organs adjacent to the tumor (4.8% vs. 2.8%, p = 0.017). Surgical aggressiveness, as shown by the proportion of patients undergoing minimally invasive surgery and adjacent organ resection, was significantly influenced by the pandemic. In addition, resectability decreased during the COVID period. These characteristics will likely influence long-term oncological outcomes, indicating the need for long-term monitoring of this cohort.

Effect of Responsiveness of Lymph Nodes to Preoperative Chemoradiotherapy in Patients With Rectal Cancer on Prognosis After Radical Resection.

BACKGROUND: The influence of lymph node (LN) response to preoperative chemoradiotherapy (PCRT) has not been well evaluated for prognosis and additional use of adjuvant treatment after PCRT in rectal cancer patients. The aim of this study was to evaluate the prognostic effect of LN regression grade (LRG) in rectal cancer after PCRT and radical resection. PATIENTS AND METHODS: From 2008 to 2011, 389 patients with rectal cancer treated with PCRT followed by radical resection were identified. The pathologic LRG (pLRG) score was determined on the basis of the proportion of tumor cells and fibrosis. The sum of the pLRG of each evaluated LN was used as the final LRG score, LRG-sum. Cox regression analysis was used to evaluate the association of LRG-sum and recurrence-free survival (RFS). RESULTS: The distribution of LRG-sum was significantly associated with tumor regression grade of the primary tumor (P < .001). LRG-sum showed different values even in patients with the same number of metastatic LNs. LRG-sum was confirmed as the most relevant associated factor among LN-related variables with RFS along with ypT stage in multivariate analysis. Patients were categorized according to the cutoff points of LRG-sum distribution: LRG1 (LRG-sum 0 to ≤3), LRG2 (LRG-sum 3 to ≤21), and LRG3 (LRG-sum >21). RFS showed a significant difference according to LRG group (P < .001) and showed more effective difference in RFS in the same ypN stage subgroup on the basis of the number of metastatic LNs. CONCLUSION: LRG was a prognostic factor of oncologic outcomes of rectal cancer. LN response to PCRT might help in prognostication and determination of treatments after PCRT.

Potential of Novel Sequence Type of Burkholderia cenocepacia for Biological Control of Root Rot of Maize (Zea mays L.) Caused by Fusarium temperatum.

In this study, two Burkholderia strains, strain KNU17BI2 and strain KNU17BI3, were isolated from maize rhizospheric soil, South Korea. The 16S rRNA gene and multilocus sequence analysis and typing (MLSA-MLST) were used for the identification of the studied strains. Strain KNU17BI2, which belonged to Burkholderia cenocepacia, was of a novel sequence type (ST) designated ST-1538, while strain KNU17BI3 had a similar allelic profile with the seven loci of Burkholderia contaminans strain LMG 23361. The strains were evaluated in vitro for their specific plant growth promoting (PGP) traits, such as zinc solubilization, phosphate solubilization, ammonia production, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, indole acetic acid (IAA) production, siderophore, and hydrolytic enzyme activity. Interestingly, the strains exhibited a positive effect on all of the tested parameters. The strains also showed broad-spectrum antifungal activity against economically important phytopathogens in the dual culture assay. Furthermore, the strains were evaluated under greenhouse conditions for their in vivo effect to promote plant growth and to suppress the root rot of maize that is caused by Fusarium temperatum on four Korean maize cultivars. The results of the greenhouse study revealed that both of the strains were promising to significantly suppress fusarium root rot and enhance plant growth promotion on the four maize cultivars. This study, for the first time, reported in vitro antifungal potential of B. cenocepacia of novel ST against economically important plant pathogens viz., F. temperatum, Fusarium graminearum, Fusarium moniliforme, Fusarium oxysporum f.sp. melonis, Fusarium subglutinans, Phytophthora drechsleri, and Stemphylium lycopersici. This is also the first report of zinc solubilization by B. cenocepacia. Moreover, the present research work reports, for the first time, about the potential of B. cenocepacia and B. contaminans to control the root rot of maize that is caused by F. temperatum. Therefore, we recommend further studies to precisely identify the bioactive chemical compounds behind such activities that would be novel sources of natural products for biological control and plant growth promotion of different crops.

Phenazine and 1-Undecene Producing Pseudomonas chlororaphis subsp. aurantiaca Strain KNU17Pc1 for Growth Promotion and Disease Suppression in Korean Maize Cultivars.

In this study, strain KNU17Pc1 was tested for its antifungal activity against Rhizoctonia solani AG-1(IA), which causes banded leaf and sheath blight (BLSB) of maize. KNU17Pc1 was tested further for its broad-spectrum antifungal activity and in vitro plant growth promoting (PGP) traits. In addition, the in vivo effects of KNU17Pc1 on reduction of BLSB severity and seedling growth promotion of two maize cultivars under greenhouse conditions were investigated. On the basis of multilocus sequence analysis (MLSA), KNU17Pc1 was confirmed as P. chlororaphis subsp. aurantiaca. The study revealed that KNU17Pc1 had strong in vitro antifungal activity and was effective toward all in vitro PGP traits except phosphate solubilization. In this study, for the first time, a strain of P. chlororaphis against Colletotrichum dematium, Colletotrichum gloeosporioides, Fusarium oxysporum f.sp. melonis, Fusarium subglutinans and Stemphylium lycopersici has been reported. Further biochemical studies showed that KNU17Pc1 was able to produce both types of phenazine derivatives, PCA and 2-OH-PCA. In addition, solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) analysis identified 13 volatile organic compounds (VOCs) in the TSB culture of KNU17Pc1, 1-undecene being the most abundant volatile. Moreover, for the first time, Octamethylcyclotetrasiloxan (D4), dimethyl disulfide, 2-methyl-1,3-butadiene and 1-undecene were detected in P. chlororaphis. Furthermore, this study reported for the first time the effectiveness of P. chlororaphis to control BLSB of maize. Hence, further studies are necessary to test the effectiveness of KNU17Pc1 under different environmental conditions so that it can be exploited further for biocontrol and plant growth promotion.

Effectiveness of multi-trait Burkholderia contaminans KNU17BI1 in growth promotion and management of banded leaf and sheath blight in maize seedling.

Plant growth promoting (PGP) bacteria enhance plant growth and are a green alternative to chemical fertilizers. In our study, an effective plant growth promoting rhizobacteria (PGPR) strain, KNU17BI1, was isolated from rhizospheric soil of maize, South Korea. The strain was tested in vitro for specific PGP and antifungal traits, such as phosphate solubilization, zinc solubilization, indole acetic acid (IAA) production, ammonia production, nitrogen fixation, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, siderophore hydrogen cyanide production (HCN) and hydrolytic enzyme activity. Furthermore, in viro antifungal activity was done in a laboratory and in vivo effect of KNU17BI1 on banded leaf and sheath blight intensity as well as plant growth promotion on maize seedling were conducted under greenhouse conditions. The strain was found to be highly effective toward all the parameters except HCN production. The strain KNU17BI1 was identified on the basis of 16S RNA and multilocus sequence analysis (MLSA) and confirmed as Burkholderia contaminans. This study for the first time demonstrated potent in vitro antifungal activity of B. contaminans against Rhizoctonia solani AG-1(IA), Pythium graminicola, Fusarium moniliforme, Alternaria alternata, Alternaria solani, Fusarium graminearum, Stemphylium botryosum Wallr, Colletotrichum dematium, Stemphylium lycopersici and Fusarium oxysporum f.sp. melonis. Furthermore, in this study, for the first time, the potential of B. contaminans stain KNU17BI1 in controlling banded leaf and sheath blight of maize caused by R. solani AG-1(IA) was reported. Therefore, further studies are warranted on the structural identification of actual compounds behind such activities that would be exploited further for biocontrol as well as plant growth promotion.

New Records of Aspergillus allahabadii and Penicillium sizovae from Crop Field Soil in Korea.

Two new records of Trichocomaceae, namely Aspergillus allahabadii and Penicillium sizovae, were isolated in 2016 during a survey of fungal diversity in different crop fields locations in Gyeongnam, Korea. These species were identified based on morphological characters and phylogenetic analysis using internal transcribed spacer region and ß-tubulin-encoding gene sequence data. A. allahabadii and P. sizovae have not yet been reported in Korea. Thus, this is the first report of these species in Korea, and their descriptions as well as details of their morphological characters are presented.

Three New Records of Ascomycetes Isolates from Field Soils in Korea.

Three new records of Ascomycota species (Chaetomium acropullum, Phialemonium globosum, Phialemonium atrogriseum) from field soils in Korea are presented in this study. These newly discovered fungal isolates were isolated from field soils from various places across Gyeongnam, Korea in 2016. All the isolates were identified and described based on morphological characteristics, and rDNA internal transcribed spacer and ß-tubulin gene sequence data. Morphological features of these fungal species were studied on different agar media: potato dextrose agar, oatmeal agar, malt extract agar, Czapek yeast extract agar, and yeast extract sucrose agar. Full description and illustrations of their morphological characters are provided. These fungal species have not officially been previously reported in Korea.

The role of radiofrequency ablation for treatment of metachronous isolated hepatic metastasis from colorectal cancer.

We investigated recurrence pattern and oncologic outcomes after treatment of metachronous isolated liver metastases from colorectal cancer according to treatment modality.We retrospectively analyzed 123 patients treated with hepatic resection and 82 patients treated with radiofrequency ablation (RFA) for metachronous isolated hepatic metastasis from colorectal cancer (HMCRC). We compared clinicopathological data, recurrence pattern, and recurrence-free survival (RFS) rates after the treatment of hepatic metastasis between patients treated with RFA and resection.The patients in the 2 groups were similar in gender, location of primary tumor, disease-free interval to hepatic metastasis, pathologic stage of primary tumor, and number of hepatic metastasis. The age was older in RFA group but it was not statistically different. The mean diameter of the largest hepatic mass was greater in the resection group than in the RFA group (3.1 vs 1.9 cm, P < 0.001). Chemotherapy after the treatment of hepatic metastasis was more commonly given in hepatic resection group (76.4% vs 62.2%, P = 0.04). Recurrence after the treatment of hepatic metastasis was not significantly different between the 2 groups (54.5% vs 65.9% in the resection and RFA groups). However, intrahepatic recurrence without extra-hepatic metastases was more common in the RFA group than in the resection group (47.5% vs 12.1%, P < 0.001). The RFS rate after the treatment of hepatic metastasis was significantly higher in resection group (48.6% vs 33.7%, P = 0.015). The size and number of hepatic metastasis, primary tumor stage, disease-free interval to hepatic metastasis, and the modality of treatment (RFA vs resection) for hepatic metastasis were confirmed as associated factors with re-recurrence after the treatment of hepatic metastasis. Among patients with solitary hepatic metastases of ≤3 cm, marginal recurrence was higher in the RFA group (3% vs 17.2%) and re-RFA was performed to achieve comparable recurrence rate (3% vs 5.2%, P = 0.662), the RFS rate was not different between the resection and RFA group (52.4% vs 53.4%, P = 0.491).Surgical resection for HMCRC showed higher RFS. However, the RFS rate in patients with a solitary hepatic metastasis of ≤3 cm was similar between the resection and RFA groups.

Gallstone ileus inducing obstructive jaundice at the afferent loop of Roux-en-Y hepaticojejunostomy after bile duct cancer surgery: a case report.

The diagnosis of gallstone ileus is occasionally challenging due to the variability of its presentation. We herein present a very rare case of gallstone ileus inducing obstructive jaundice at the afferent loop of Roux-en-Y hepaticojejunostomy after 10 years of bile duct cancer surgery. We describe the case of a 74-year-old Korean woman with obstructive jaundice, treated conservatively. She showed severely impaired liver function test and obstructive jaundice. The computed tomography (CT) scan led to a diagnosis of very rare type of gallstones ileus at the afferent jejunal loop. Since the clinical manifestation was improved, we decided to observe her closely. On the next follow-up CT scan, the gallstone disappeared with mild distension of the afferent bowel loop, implicating spontaneous passage of the gallstone. She recovered and returned to normal life after 10 days of initiation of clinical manifestations. We presume that the gallstone may enter the afferent jejunal loop through the hepaticojejunostomy and later increase in size. The presence of narrow tract of intestine may facilitate the incidence of gallstone ileus. It appears to be the first report on this rare type of gallstone ileus inducing obstructive jaundice.

Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children.

There have been no pharmacokinetic parameters and blood-brain equilibration rate constant (k e0) of propofol obtained in a single population of children, by which propofol can be administered using a target effect-site concentration controlled infusion. Thirty-nine, American Society of Anesthesiologists Physical Status 1-2 children aged 2-12 years were given an intravenous bolus of propofol (3 mg kg(-1)), followed by infusion (200 µg kg(-1) min(-1)). Arterial drug concentrations and bispectral index (BIS) values were measured. Population pharmacokinetic and pharmacodynamic analysis was performed using nonlinear mixed effects modeling. External model validation was performed in a separate population of children. A two-compartment model and a sigmoid E max model directly linked by an effect compartment well described the time courses of propofol concentration and BIS. The estimates of parameters were: V 1 (L) = 1.69, V 2 (L) = 27.2 + 0.929 × (weight - 25), Cl (L min(-1)) = 0.893 × (weight/23.6)(0.966), Q (L min(-1)) = 1.3; E 0 = 76.9; E max = 35.4, Ce 50 (µg mL(-1)) = 3.47 - (0.095 × age) - (1.63 × mean infusion rate of remifentanil in µg kg(-1) min(-1)); γ = 2.1; and k e0 (min(-1)) = 0.371. Pooled biases (95 % CI) of the target effect-site concentration controlled infusion system of propofol was -20.2 % (-23.3 to -18.1 %) and pooled inaccuracy was 30.4 % (28.6-32.7 %). Pooled biases of BIS prediction was -6.8 % (-9.1 to -4.1 %) and pooled inaccuracies was 19.1 % (17.5-20.9 %).The altered weight-based dose requirements of propofol are well described pharmacokinetically, and pharmacodynamically. Predictive performances of the TCI system in this study were clinically acceptable.

Effects of hesperidin loaded poly(lactic-co-glycolic acid) scaffolds on growth behavior of costal cartilage cells in vitro and in vivo.

It has been widely accepted that costal cartilage cells (CCs) have more excellent initial proliferation capacity than articular cartilage cells. Biodegradable synthetic polymer poly(lactic-co-glycolic acid) (PLGA) was approved by Food and Drug Administration. Hesperidin has antifungal, antiviral, antioxidant, anti-inflammatory, and anticarcinogenic properties. Hesperidin loaded (0, 3, 5, and 10 wt.%) PLGA scaffolds were prepared and in vitro and in vivo properties were characterized. Scaffolds were seeded with CCs isolated from rabbit, which were kept in culture to harvest for histological analysis. Hesperidin/PLGA scaffolds were also implanted in nude mice for 7 and 28 days. Assays of 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfo-phenyl)-2H-tetrazolium, monosodium salt (WST), and scanning electron microscope were carried out to evaluate attachment and proliferation of CCs in hesperidin/PLGA scaffolds. Glycosaminoglycan assay was performed to confirm the effects of hesperidin on extracellular matrix formation. Reverse-transcriptase polymerase chain reaction was carried out to confirm the expression of the specific genes for CCs. In these results, we demonstrated that cell attachment and proliferation on hesperidin/PLGA scaffolds were more excellent compared with on PLGA scaffold. Specially, 5 wt.% hesperidin/PLGA scaffold represented the best results among other scaffolds. Thus, 5 wt.% hesperidin/PLGA scaffold will be applicable to tissue engineering cartilage.