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Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Abstract Background Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). Methods A multicenter randomized phase II trial involving 364 patients with LARC (cT3–4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45–50.4 Gy in 25–28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2–5 weeks from the last cycle of chemotherapy in the experimental arm and 6–8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. Discussion This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. Trial registration This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Abstract Background The effect of fecal stream diversion on the gut microbiota is still uncertain. The present study was designed to assess the effect of fecal stream diversion on the composition of the gut microbiota in patients with colorectal cancer. We included patients undergoing left-sided colorectal cancer surgery with (ileostomy group) or without (control group) diverting ileostomy. Fecal samples were collected from 10 patients in each group before surgery (t 1 ) and after ileostomy repair in the ileostomy group and 6–12 months after the initial surgery in the control group (t 2 ). The fecal microbiota was assessed using 16S rRNA sequencing, and changes in the composition of the fecal microbiota were compared between the two groups. Results Alpha diversity analysis revealed that the complexity of fecal microbiota decreased between t 1 and t 2 only in the ileostomy group. Beta diversity analysis also showed dissimilarity between t 1 and t 2 only in the ileostomy group. The composition of the microbiota was similar between the two groups at t 1 . However, at t 2 , the ileostomy group had lower proportion of beneficial bacteria (Lachnospiraceae, 3.8% vs. 29.9%, p

Abstract Background Minimally invasive surgery has become popular as a surgical approach for colorectal cancer because it has fewer complications related to the abdominal incision and perioperative complications. However, the incidence of incisional hernias in laparoscopic surgery has been reported to be similar to that in open surgery. We developed a new method, the non-muscle-cutting periumbilical transverse incision, for a small incision in laparoscopic colon cancer surgery. This study aims to evaluate the effectiveness of the non-muscle-cutting periumbilical transverse incision in comparison with the midline incision in reducing the incidence of an incisional hernia in patients undergoing laparoscopic colon cancer surgery. Methods This is an open-label, multi-centre, parallel, superiority, and randomised trial. Altogether, 174 patients will be allocated in a 1:1 ratio to either the midline incision or the non-muscle-cutting periumbilical transverse incision group, after stratifying by the location of the tumour (right- or left-sided). The primary outcome of this study is the incidence of incisional hernias (both symptomatic and radiologic hernias) at 12 months after surgery. The secondary outcomes include operative outcomes, 30-day postoperative complications, pathological results, and patient-reported outcomes (short form-12 health survey questionnaire and body image questionnaire). Both primary (intention-to-treat) and secondary (as-treated principles) analyses will be performed for all outcomes. The statistical significance level was set at p

As the demand for transformer applications increases rapidly, technologies to solve memory bottlenecks are attracting attention. One of them is an in-DRAM Processing-In-Memory (PIM) architecture to perform the computation inside DRAM. Major DRAM makers introduce the PIM samples, executing all banks’ computations simultaneously to maximize the internal DRAM bandwidth for achieving the highest performance. However, the realization as a commercial product is problematic since the all-bank execution does not concurrently perform non-PIM applications during the PIM execution with PIM memory, thus separating their memory space. This paper proposes a BL-PIM architecture to increase the burst length (BL) of memory requests inside a bank to maximize internal bandwidth and overlap the computation across banks, thus achieving all-bank performance. On the other hand, outside a bank, it seems not to increase the BL, thus allowing us to preserve the data consistency in memory hierarchy and execute non-PIM and PIM applications together with PIM memory. Also, the memory-intensive PIM computation using larger BL significantly reduces their outstanding memory requests, thus minimizing the performance interference with other applications. We carefully extend the DRAM timing diagram and develop the cooperation mechanism between a memory controller and a PIM device. We implemented the BL-PIM architecture on FPGA and compared the performance with real machines using four transformer models and eight compute and memory-bound SPEC benchmarks. We achieved the BL-PIM performance up to 28.9x and 12.0x faster than the CPU single-thread and multi-threaded execution in the transformer models. Also, when we increased the burst length by 16 times as the maximum, the BL-PIM was 1.2x faster than the ideal all-bank PIM execution. We also experimented with the multi-workload execution using the SPEC benchmarks, showing that our architecture can minimize performance interference. To our knowledge, the study of the PIM’s multi-workload execution is the first in public.

Processing-in-memory (PIM) has attracted attention to overcome the memory bandwidth limitation, especially for computing memory-intensive DNN applications. Most PIM approaches use the CPU’s memory requests to deliver instructions and operands to the PIM engines, making a core busy and incurring unnecessary data transfer, thus, resulting in significant offloading overhead. DMA can resolve the issue by transferring a high volume of successive data without intervening CPU and polluting the memory hierarchy, thus perfectly fitting the PIM concept. However, the small computing resources of DRAM-based PIM devices allow us to transfer only small amounts of data at one DMA transaction and require a large number of descriptors, thus still incurring significant offloading overhead. This paper introduces PIM Instruction Set Architecture (ISA) using a DMA descriptor called PISA-DMA to express a PIM opcode and operand in a single descriptor. Our ISA makes PIM programming intuitive by thinking of committing one PIM instruction as completing one DMA transaction and representing a sequence of PIM instructions using the DMA descriptor list. Also, PISA-DMA minimizes the offloading overhead while guaranteeing compatibility with commercial platforms. Our PISA-DMA eliminates the opcode offloading overhead and achieves 1.25x, 1.31x, and 1.29x speedup over the baseline PIM at the sequence length of 128 with the BERT, RoBERTa, and GPT-2 models, respectively, in ONNX runtime with real machines. Also, we study how our proposed PISA affects performance in compiler optimization and show that the operator fusion of matrix-matrix multiplication and element-wise addition achieved 1.04x speedup, a similar performance gain using conventional ISAs.

The lipophilicity of a peptide drug can be considerably increased by hydrophobic ion pairing with amphiphilic counterions for successful incorporation into lipid-based formulations. Herein, to enhance the oral absorption of insulin (INS), a self-microemulsifying drug delivery system (SMEDDS) formulation was developed. Prior to optimization, INS was complexed with sodium n-octadecyl sulfate (SOS) to increase the loading into the SMEDDS. The INS–SOS complex was characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and its dissociation behavior. The SMEDDS was optimized using a D-optimal mixture design with three independent variables including Capmul MCM (X1, 9.31%), Labrasol (X2, 49.77%), and Tetraglycol (X3, 40.92%) and three response variables including droplet size (Y1, 115.2 nm), INS stability (Y2, 46.75%), and INS leakage (Y3, 17.67%). The desirability function was 0.766, indicating excellent agreement between the predicted and experimental values. The stability of INS-SOS against gastrointestinal enzymes was noticeably improved in the SMEDDS, and the majority of INS remained in oil droplets during release. Following oral administration in diabetic rats, the optimized SMEDDS resulted in pharmacological availabilities of 3.23% (50 IU/kg) and 2.13% (100 IU/kg). Thus, the optimized SMEDDS is a good candidate for the practical development of oral delivery of peptide drugs such as INS.

Abstract Background Although many efforts have been made to decrease the incidence of anastomotic leak (AL), it remains one of the most serious complications of rectal cancer surgery. Many previous studies have reported an association between the ligation level of the inferior mesenteric artery (IMA) (high or low) and the incidence of AL after rectal cancer surgery. However, we cannot draw a solid conclusion because of the low quality and heterogeneity of those studies. Therefore, this study aims to investigate the impact of the IMA ligation level on the occurrence of AL after minimally invasive anterior resection of rectal cancer. Methods/design Patients with primary rectal cancer without distant metastases will be included after screening. They will be randomly assigned (1:1) to receive high or low ligation of the IMA. The primary endpoint is AL incidence; secondary endpoints are quality of life; urinary, sexual, and defecatory functions; and 3-year disease-free survival. We hypothesized that the incidence rate of AL would be 15% and 5% in the high- and low-ligation groups, respectively. With a two-sided α of 0.05 and a power of 0.8, the sample size is calculated to be 314 patients (157 per group), considering a 10% dropout rate. Discussion Although many studies have compared the short- and long-term outcomes of high and low ligation of the IMA in rectal cancer surgery, it is still debatable. This trial aims to help draw a more solid conclusion regarding the association between the IMA ligation level and AL incidence after rectal cancer surgery. We also hope to contribute to standardizing the method of rectal cancer surgery in this trial. Trial registration Clinical Research Information Service KCT0003523. Registered on February 18, 2019

Abstract Background A targeted co-administration system of docetaxel (DTX) and curcumin (CUR) using a PEG-modified RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated nanostructured lipid carrier (P/R-NLC) was constructed to exert synergistic anticancer effects against chemoresistant breast cancer. Results DTX- or CUR-loaded NLCs and P/R-NLCs were prepared using the solvent emulsification–evaporation method. NLCs showed homogeneous spherical morphology with nano-sized dispersion ( 95%); drug loading (8 − 18%). All NLC formulations were stable for 4 weeks under the storage conditions at 4 °C. Drug release was diffusion-controlled, revealing the best fit to the Higuchi equation. DTX- or CUR-loaded formulations showed dose-dependent cytotoxicity. The DTX/CUR combination (1:3 w/w) in P/R-NLC formulations exhibited the strongest synergism in both MCF7 and MCF7/ADR cells with combination index values of 0.286 and 0.130, respectively. Co-treatment with DTX- or CUR-P/R-NLCs increased apoptosis in both cell lines exhibited the superior synergistic inhibitory effect on MCF7/ADR three-dimensional spheroids. Finally, in OVCAR3-xenografted mouse models, co-treatment with DTX- or CUR-loaded P/R-NLCs significantly suppressed tumor growth compared to the other treatment groups. Conclusions Co-administration of DTX/CUR (1:3 w/w) using P/R-NLCs induced a synergistic effect against chemoresistant cancer cells. Graphical Abstract

Purpose: Pre-operative evaluation identifying clinical-stage affects the decision regarding the extent of surgical resection in right colon cancer. This study was designed to predict a proper surgical resection through the prognosis of clinical Stage I right colon cancer. Patients and Methods: We included patients who were diagnosed with clinical and pathological Stage I right-sided colon cancer, including appendiceal, caecal, ascending, hepatic flexure and proximal transverse colon cancer, between August 2010 and December 2016 in two tertiary teaching hospitals. Patients who underwent open surgeries were excluded because laparoscopic surgery is the initial approach for colorectal cancer in our institutions. Results: Eighty patients with clinical Stage I and 104 patients with pathological Stage I were included in the study. The biopsy reports showed that the tumour size was larger in the clinical Stage I group than in the pathological Stage I group (3.4 vs. 2.3 cm, P < 0.001). Further, the clinical Stage I group had some pathological Stage III cases (positive lymph nodes, P = 0.023). The clinical Stage I group had a higher rate of distant metastases (P = 0.046) and a lower rate of overall (P = 0.031) and cancer-specific survival (P = 0.021) than the pathological Stage I group. Compared to pathological Stage II included in the period, some of the survival curves were located below the pathological Stage II, but there was no statistical difference. Conclusion: The study results show that even clinical Stage I cases, radical resection should be considered in accordance with T3 and T4 tumours.

Processing-in-Memory (PIM) has been actively studied to overcome the memory bottleneck by placing computing units near or in memory, especially for efficiently processing low locality data-intensive applications. We can categorize the in-DRAM PIMs depending on how many banks perform the PIM computation by one DRAM command: per-bank and all-bank. The per-bank PIM operates only one bank, delivering low performance but preserving the standard DRAM interface and servicing non-PIM requests during PIM execution. The all-bank PIM operates all banks, achieving high performance but accompanying design issues like thermal and power consumption. We introduce the memory-computation decoupling execution to achieve the ideal all-bank PIM performance while preserving the standard JEDEC DRAM interface, i.e., performing the per-bank execution, thus easily adapted to commercial platforms. We divide the PIM execution into two phases: memory and computation phases. At the memory phase, we read the bank-private operands from a bank and store them in PIM engines’ registers bank-by-bank. At the computation phase, we decouple the PIM engine from the memory array and broadcast a bank-shared operand using a standard read/write command to make all banks perform the computation simultaneously, thus reaching the computing throughput of the all-bank PIM. For extending the computation phase, i.e., maximizing all-bank execution opportunity, we introduce a compiler analysis and code generation technique to identify the bank-private and the bank-shared operands. We compared the performance of Level-2/3 BLAS, multi-batch LSTM-based Seq2Seq model, and BERT on our decoupled PIM with commercial computing platforms. In Level-3 BLAS, we achieved speedups of $75.8\times $ , $1.2\times $ , and $4.7\times $ compared to CPU, GPU, and the per-bank PIM and up to 91.4% of the ideal all-bank PIM performance. Furthermore, our decoupled PIM consumed less energy than GPU and the per-bank PIM by 72.0% and 78.4%, but 7.4%, a little more than the ideal all-bank PIM.

Blood group mismatch in veterinary medicine is a significant problem in blood transfusion, sometimes leading to severe transfusion reactions and even patient death. Blood groups vary from species to species and there are three known blood groups in cats: A, B and AB. While A-type cats are most common, there is a shortage of feline B-type blood groups in cats. By using methoxy polyethylene glycol (mPEG) to protect antigenic epitopes on red blood cells (RBCs), we aimed to find the optimal conditions for the production of feline universal RBCs. The surfaces of feline A-type RBCs were treated with mPEG at various molecular weights and concentrations. Agglutination tests showed that the coating of feline A-type RBCs with mPEG of 20 kDa and 2 mM blocked hemagglutination to feline anti-A alloantibodies over 8 h. While no differences in RBC size and shape between intact and mPEG-treated RBCs were seen, coating RBCs with mPEG inhibited the binding of feline anti-A alloantibodies. Furthermore, the mPEG-treated RBCs did not cause spontaneous hemolysis or osmotic fragility, compared to control RBCs. According to a monocyte monolayer assay, mPEG treatment significantly reduced feline anti-A antibody-mediated phagocystosis of RBCs. These results confirm the potential of using activated mPEG on feline A-type RBC to create universal erythrocytes for transfusion to B-type cats.

From the perspective of survival outcomes, the cancer survival of colorectal cancer (CRC) in the whole stage has improved. Peritoneal metastasis (PM) is found in approximately 8% to 15% of patients with CRC, with a poorer prognosis than that associated with other sites of metastases. Randomized controlled trials and up-to-date meta-analyses provide firm evidence that cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) could significantly improve overall survival compared with systemic chemotherapy alone in selected patients with CRC-PM. Practical guidelines recommend that the management of CRC-PM should be led by a multidisciplinary team carried out in experienced centers and consider CRS plus HIPEC for selected patients. In this review, we aim to provide the latest results of land mark studies and an overview of recent insights with regard to the management of CRC-PM.

Abstract Background Prompt and accurate identification of carbapenemase production is essential for appropriate treatment and infection control. NG-Test Carba 5 (termed herein “Carba 5”; NG Biotech, Guipry, France) is a multiplex immunochromatographic assay for the rapid phenotypic identification of five major carbapenemases (KPC, NDM, VIM, IMP, and OXA-48-like) from bacterial isolates. This study aimed to evaluate the diagnostic performance of Carba 5 and its impact on the turn-around-time in a clinical microbiology laboratory. Results Carba 5 was retrospectively evaluated using 78 carbapenemase producers and 23 non-carbapenemase producers confirmed by PCR and sequencing. The performance and time required for carbapenemase identification were prospectively evaluated using 47 carbapenem resistant Enterobacteriaceae isolates, and the results were compared to those obtained using Xpert Carba-R (Cepheid, Sunnyvale, CA, USA). For the bacterial isolates included in retrospective and prospective evaluation, the Carba 5 assay correctly identified 147 isolates except one isolate with a sensitivity of 99.13% (95% CI 95.25–99.98%) and specificity of 100% (95% CI 89.42–100%). The Carba 5 assay missed one VIM-1 among 13 VIM producers. The assay showed a sensitivity of 92.31% (95% CI 63.97–99.81%) for detecting VIM and 100% for detecting KPC, NDM, OXA-48-like, and IMP. Compared to the Xpert Carba-R assay, Carba 5 exhibited 100% agreement and was more time-efficient (median time 24 min vs. 1 h 11 min). Conclusions The Carba 5 assay has potential as an alternative to molecular methods for detecting major carbapenemases from bacterial isolates in a clinical microbiology laboratory. Compared to the Xpert Carba-R, Carba 5 turns out to be more affordable and time-efficient while showing a comparable performance, and may accelerate therapeutic and infection control decisions.

Background/Aims Several studies have shown that colorectal neoplasms (CRN) including colorectal cancer (CRC) may be prevalent in patients with gastric cancer. However, in most of these studies, colonoscopy to investigate the prevalence of CRN was performed prior to surgery. We aimed to investigate whether CRN was more prevalent in postgastrectomy gastric cancer patients than in healthy individuals. Methods We reviewed the medical records of those patients within a cohort of gastric cancer patients with gastrectomy who underwent colonoscopy between 2016 and 2017. Controls age- and sex-matched with gastric cancer patients at a 2:1 ratio were identified among those who underwent colonoscopy at a health-promotion center. The frequencies of CRN, advanced CRN (ACRN), and CRC among patients with gastrectomy were compared with those in the control subjects. A total of 744 individuals (gastric cancer, 248; control, 496) were included. Results The rates of CRN and ACRN in the gastric cancer group were higher than those in the healthy individuals (CRN, 47.6% vs. 34.7%, P

Purpose: The colon originates from the midgut and hindgut, with subsequent differentiation into the right and left colon. The embryology, clinical symptoms, incidence, molecular pathways, and oncologic outcomes differ between right and left colorectal cancers. However, the differences have not been fully accepted. Aim of the Study: This study compared short- and long-term outcomes between right and left colon cancers. Materials and Methods: This study included 966 patients who underwent laparoscopic resection with radical lymph node dissection for stage I, II, and III colon cancers between 2009 and 2014 at a tertiary teaching hospital. We excluded cases with fewer than 12 retrieved lymph nodes, emergency operations, synchronous or multiple cancers, and those located in the transverse colon and rectum. Results: The right colon group included 343 (35.5%) patients and the left colon group 623. Female patients had a high incidence of right colon cancer (p

Purpose This study aimed to evaluate the relationship between high-output stomas (HOSs), postoperative ileus (POI), and readmission after rectal cancer surgery with diverting ileostomy. Methods We included 302 patients with rectal cancer who underwent restorative resection with diverting ileostomy between January 2011 and December 2015. HOSs were defined as stomas with ≥ 2,000 mL/day output. We analyzed predictive factors for readmission of these patients. Results Forty-eight patients (15.9%) had HOSs during the hospital stay, and 41 patients (13.6%) experienced POI. HOSs were strongly associated with POI (45.8% vs. 7.5%, P < 0.001). The all-cause readmission rate was 16.9%, with 19 (6.3%) and 20 (6.6%) experiencing ileus and acute kidney injury, respectively. HOSs (27.1% vs. 15.0%, P = 0.040) and POI (34.1% vs. 14.2%, P = 0.002) were associated with all-cause readmission, and POI was associated with readmission with ileus (17.1% vs. 4.6%, P = 0.007). POI was an independent risk factor for all-cause readmission (adjusted odds ratio [OR], 2.640; 95% confidence interval [CI], 1.162 to 6.001; P = 0.020) and readmission with ileus (adjusted OR = 3.869; 95% CI 1.387 to 10.792; P = 0.010). Conclusion POI was associated with readmission, particularly for subsequent ileus, in patients with diverting ileostomy. We should make efforts to reduce POI, such as strong control of HOSs, to prevent readmission.

Abstract Background Very few studies have been conducted on the treatment strategy for enlarged paraaortic lymph nodes (PALNs) incidentally detected during surgery. The purpose of this study was to investigate the benefit of lymph node dissection in patients with incidentally detected enlarged PALNs. Methods We retrospectively reviewed patients with left colon and rectal cancer who underwent surgical resection with PALN dissection between January 2010 and December 2018. The predictive factors for pathologic PALN metastasis (PALNM) were analyzed, and survival analyses were conducted to identify prognostic factors. Results Among 263 patients included, 19 (7.2%) showed pathologic PALNM and 5 (26.33%) had enlarged PALNs incidentally detected during surgery. These 5 patients accounted for 2.2% of 227 patients who had no evidence of PALNM on preoperative radiologic examination. Radiologic PALNM (odds ratio [OR] 12.737, 95% confidence interval [CI] 3.472–46.723) and radiologic distant metastasis other than PALNM (OR = 4.090, 95% CI 1.011–16.539) were independent predictive factors for pathologic PALNM. Pathologic T4 stage (hazard ratio [HR] 2.196, 95% CI 1.063–4.538) and R2 resection (HR 4.643, 95% CI 2.046–10.534) were independent prognostic factors for overall survival (OS). In patients undergoing R0 resection, pathologic PALNM was not associated with 5-year OS (90% vs. 82.2%, p = 0.896). Conclusion Dissection of enlarged PALNs incidentally detected during colorectal surgery may benefit patients with favorable survival outcomes.

The simultaneous drug delivery efficiency of a co-loaded single-carrier system of docetaxel (DTX)- and tariquidar (TRQ)-loaded nanostructured lipid carrier (NLC) functionalized with PEG and RIPL peptide (PRN) (D^T-PRN) was compared with that of a physically mixed dual-carrier system of DTX-loaded PRN (D-PRN) and TRQ-loaded PRN (T-PRN) to overcome DTX mono-administration-induced multidrug resistance. NLC samples were prepared using the solvent emulsification evaporation technique and showed homogeneous spherical morphology, with nano-sized dispersion (95% encapsulation efficiency and 73–78 µg/mg drug loading). In vitro cytotoxicity was concentration-dependent; D^T-PRN exhibited the highest MDR reversal efficiency, with the lowest combination index value, and increased the cytotoxicity and apoptosis in MCF7/ADR cells by inducing cell-cycle arrest in the G2/M phase. A competitive cellular uptake assay using fluorescent probes showed that, compared to the dual nanocarrier system, the single nanocarrier system exhibited better intracellular delivery efficiency of multiple probes to target cells. In the MCF7/ADR-xenografted mouse models, simultaneous DTX and TRQ delivery using D^T-PRN significantly suppressed tumor growth as compared to other treatments. A single co-loaded system for PRN-based co-delivery of DTX/TRQ (1:1, w/w) constitutes a promising therapeutic strategy for drug-resistant breast cancer cells.

Abstract Background Current guidelines recommend the prescription of immune-enriched oral nutritional supplements for malnourished patients before major gastrointestinal surgery. However, the benefit of preoperative immunonutrition is still controversial. This randomized controlled trial aims to evaluate the effect of preoperative immunonutrition on the outcomes of surgery for colon cancer. Methods/design Patients with primary colon cancer will be included as study participants after screening. They will be randomly assigned (in a ratio of 1:1) to receive preoperative immunonutrition added to the normal diet (experimental arm) or consume normal diet alone (control arm). Patients in the experimental arm will receive oral supplementation (400 mL/day) with arginine and ω-3 fatty acids for 7 days before elective surgery. The primary endpoint is the rate of infectious complications, while the secondary endpoints are postoperative complication rate, change in body weight, length of hospital stay, and nature of fecal microbiome. The authors hypothesize that the rate of infectious complications would be 13% in the experimental arm and 30% in the control arm. With a two-sided alpha of 0.05 and a power of 0.8, the sample size is calculated as 176 patients (88 per arm). Discussion Although there have been many studies demonstrating significant benefits of preoperative immunonutrition, these were limited by a small sample size and potential publication bias. Despite the recommendation of immunonutrition before surgery in nutritional guidelines, its role in reduction of rate of infectious complications is still controversial. This trial is expected to provide evidence for the benefits of administration of preoperative immunonutrition in patients with colon cancer. Trial registration Clinical Research Information Service KCT0003770 . Registered on 15 April 2019.

Background: The disease burden caused by Mycobacterium tuberculosis (MTB) complex continues to decrease in most countries. However, the diseases caused by the nontuberculous mycobacteria (NTM) become a public health problem. This study aimed to compare the diagnostic accuracy of three real-time PCR assays: Advansure TB/NTM real-time PCR kit (LG Chem., Korea), Genedia MTB/NTM detection kit (Green Cross MS, Korea), and PowerChek MTB/NTM Real-time PCR kit (Kogenebiotech, Korea) for the detection of MTB complex and NTM. Methods: Total 102 acid-fast bacilli (AFB) smear-positive and 177 smear-negative specimens from Korea University Medical Center, Guro Hospital, were enrolled. The AFB smear-positive and negative specimens were collected from November 2016 to October 2017 and November to December 2018, respectively. DNA extraction was performed using Genedia Mycobacteria DNA prep Kit (Green Cross MS). The statistical analysis was performed using MedCalc 18.11.6 (MedCalc, Ostend, Belgium). Results: Among 261 specimens, 64 showed MTB complex growth and 28 exhibited NTM growth. The sensitivity, specificity, positive predictive value, and negative predictive value of Advansure/Genedia/PowerChek kits for MTB were 96.9%/95.3%/96.9%, 98.5%/99.5%/98.5%, 58.9%/80.9%/58.9%, and 99.9%/99.9%/99.9%. Whereas those for NTM detection were 81.5%/44.4%/88.9%, 99.6%/100.0%/98.7%, 57.3%/100.0%/32.8% and 99.9%/99.6%/99.9%, respectively. The area under the receiver operating characteristic curve of Advansure and PowerChek for NTM detection was statistically different from that of Genedia (P

Summary: Background: Among rectal cancer patients, some of good responders after neoadjuvant chemoradiotherapy (nCRT) are considered for non-operative treatments to avoid postoperative morbidities and permanent stoma. However, oncologic feasibility of non-operative treatment has not been fully understood. Methods: From 2008 to 2017, we retrospectively reviewed patient's records who had lower or mid rectal cancer and diagnosed to clinical complete response by magnetic resonance imaging after nCRT. Clinical differences and oncologic outcomes were compared among Radical surgery (RS), Local excision (LE) and Wait-and-see (WS) group. Results: Number of 129, 25, 15 patients included to RS, LE, WS groups. Local recurrence was frequent type of recurrence in both of LE and WS group (RS; 31.3%, LE; 80%, WS; 66.7%), and many patients in WS group omitted salvage treatment (RS; 75%, LE; 100%, WS; 33.3%). 5-years local-recurrence/disease-free survival rate (LRFS, DFS) between RS and LE were similar between each group, but WS showed significantly inferior outcomes than that of RS (LRFS; p = 0.001, DFS; p = 0.001). In multivariate analysis, WS protocol (OR; 7.163, 95% CI; 1.995–25.715) and cT4 stage (OR; 8.206, 95% CI; 1.596–42.198) were independent factors for LRFS. Conclusions: Wait-and-see group showed high rate of rejection of salvage treatments for recurrence, and poor oncologic outcomes. However, recent low-level evidences reported favorable outcome of WS protocol when salvage treatment was followed after recurrence. It seems that the application of WS protocol should be postponed until the results of randomized-controlled trials are available. Local excision seems to be good alternative option to radical surgery when salvage treatment is followed. Keywords: Rectal cancer, Complete response, Local excision, Wait-and-see

Purpose The bowel frequency of patients who had undergone rectal resection might be difficult to distinguish from the diarrhea of Clostridium difficile infection (CDI). The change of bowel movement following rectal surgery has been a challenge for the diagnosis of CDI and scarce studies discussed this diagnostic difficulty. Methods From January 2004 to January 2018, a total of 8,327 patients in a single tertiary colorectal cancer center was evaluated for CDI, and their medical records were ret rospectively reviewed. Bowel frequency and treatment outcomes were compared between the rectal resection group (RG) and colectomy group (CG). Diagnostic time was defined as the time interval between first diarrhea (more than three times a day) and pathologic confirmation date of CDI. Results CDI incidence was 2.3% (17/752) vs. 0.41% (31/7,575) between RG and CG (P

Purpose The aim of this study was to assess oncological outcomes of postoperative radiotherapy plus chemotherapy (CRT) versus chemotherapy alone (CTx) in stage II or III upper rectal cancer patients who underwent curative surgery. Methods We retrospectively reviewed 263 consecutive patients with pathologic stage II or III upper rectal cancer who underwent primary curative resection with postoperative CRT or CTx from January 2008 to December 2014 at Chonnam National University Hwasun Hospital. Multivariate and propensity score matching analyses were used to reduce selection bias. Results Median follow-up was 48.1 months for the entire cohort and 53.5 months for the matched cohort. In subgroup analysis of the propensity score matched cohort, the 3-year local recurrence-free survival was 94.1% (95% confidence interval [CI], 87.8%–100%) in the CRT group and 90.1% (95% CI, 82.8%–97.9%) in the CTx group (P = 0.370). No significant difference in disease-free survival was observed according to treatment type. On multivariate analysis, circumferential resection margin involvement (hazard ratio [HR], 2.386; 95% CI, 1.190–7.599; P = 0.032), N stage (HR, 6.262; 95% CI, 1.843–21.278, P = 0.003), and T stage (HR, 5.896, 95% CI, 1.298–6.780, P = 0.021) were identified as independent risk factors for local recurrence of tumors of the upper rectum. Conclusion Omission of radiotherapy in an adjuvant treatment setting may not jeopardize oncologic outcomes in stages II and III upper rectal cancer.

Purpose Treatment after failure of circumferential resection margin (CRM) conversion after preoperative chemoradiotherapy (pCRT) for locally advanced rectal cancer (LARC) has not been evaluated well. We conducted a single‐center, retrospective analysis to fill this information gap. Methods From 2008 to 2016, we included 112 patients who had predictive CRM involvement on baseline magnetic resonance imaging (MRI) and who underwent surgery following pCRT for LARC. Baseline and posttreatment radiologic and clinical factors were analyzed. Results Of 493 patients with LARC, 112 had CRM involvement by baseline MRI (mrCRM). In 40 patients (35.7%), mrCRM involvement was converted as negative posttreatment CRM (ymrCRM−). Multivariate analysis showed the risk factors for persistent CRM involvement (ymrCRM+) after pCRT were extramural venous invasion (mrEMVI+) (P = 0.030) and lower tumor location (P = 0.007). In addition, persistent CRM involvement after pCRT was an independent risk factor for predicting pathologic CRM involvement. The Cox proportional hazard model showed baseline positive mrEMVI remained significant for disease-free survival (DFS) (P < 0.001). On posttreatment MRI, abdominoperineal resection (P = 0.031), intersphincteric resection (P = 0.006), and persistent CRM involvement (P = 0.001) remained significant for local recurrence-free survival. With regard to DFS, persistent CRM involvement (P = 0.048) and positive EMVI on posttreatment MRI (ymrEMVI) (P = 0.014) were significant. In the patient subgroup with persistent CRM involvement, 5-year DFS in patients with mrEMVI and ymrEMVI was 29.8% and 21.2%, respectively. Conclusion Patients who fail to convert to negative CRM have extremely poor oncologic outcomes. Lower tumor height and negative mrEMVI status were good responders to ymrCRM conversion. Our results suggest that these patients require a more intensive treatment modality.

The computing domain of today's computer systems is moving very fast from arithmetic to data processing as data volumes grow exponentially. As a result, processing-in-memory (PIM) studies have been actively conducted to support the data processing in or near memory devices to address the limited bandwidth and high power consumption due to data movement between CPU/GPU and memory. However, most PIM studies so far have been conducted in a way that the processing units are designed only as an accelerator on the base die of 3D-stacked DRAM, not involved inside memory while not servicing the standard DRAM requests during the PIM execution. Therefore, in this paper, we show how to design and operate the PIM computing units inside DRAM by effectively coordinating with standard DRAM operations while achieving the full computing performance and minimizing the implementation cost. To make our goals, we extend a standard DRAM state diagram to depict the PIM behaviors in the same way as standard DRAM commands are scheduled and operated on the DRAM devices and exploit several levels of parallelism to overlap memory and computing operations. Also, we present how the entire architecture layers from applications to operating systems, memory controllers, and PIM devices should work together for the effective execution by applying our approaches to our experiment platform. In our HBM2-based experimental platform to include 16-cycle MAC (Multiply-and-Add) units and 8-cycle reducers for a matrix-vector multiplication, we achieved 406% and 35.2% faster performance by the all-bank and the per-bank schedulings, respectively, at (1024 × 1024) × (1024 × 1) 8-bit integer matrix-vector multiplication than the execution of only its operand burst reads assuming the external full DRAM bandwidth. It should be noted that the performance of the PIM on a base die of a 3D-stacked memory cannot be better than that provided by the full bandwidth in any case.

Situs inversus is a rare hereditary disorder in which various anomalies have been reported with internal rotation abnormalities. This case involved an 85-year-old woman who had been diagnosed with transverse colon cancer and who underwent reduced-port laparoscopic surgery. All intra-abdominal organs were reversed left to right and right to left. The aberrant midcolic artery was identified during surgery. The total surgery time was 170 minutes, and the patient lost 20 mL of blood. The patient was discharged on the 8th postoperative day without complications.

Purpose: Medial meniscus posterior root tear (MMPRT) should be repaired to the correct position as possible to maintain hoop tension of the meniscus. In this study, we propose a comparison of the outcome between the medial tunnel and the lateral tunnel in the pullout suture technique using the tibial tunnel for anatomical repair of posterior root tear of medial meniscus. Methods: From April 2010, of patients who underwent pullout suture, 51 cases (24 medial tunnel group (MTG) and 27 lateral tunnel group (LTG)) were able to follow-up with second look arthroscopy. Original Coronal Ratio of Root Attachment (CRORA) was defined as the ratio of the distance from the medial edge of the tibial plateau to the root attach site divided by the entire tibial medial–lateral width on preoperative computed tomography. Error between postoperative CRORA and original CRORA was calculated. We compared this error, clinical outcome, and arthroscopic finding between MTG and LTG. Results: The mean error ratio of postoperative CRORA divided by original CRORA was 0.86 ± 0.11 in MTG, which was significantly ( p = 0.001) lower than that (1.02 ± 0.06) in LTG. The mean value of the root attach point in the MTG with a post/original CRORA value of 0.86 ± 0.11 means statistically significant medialization after the operation. There was no statistically significant difference in changes of International Knee Documentation Committee (IKDC) and Lysholom score between MTG and LTG. The difference between the two groups of arthritis progression was not statistically significant. Conclusion: In patients with MMPRT, CRORA may provide a basis for coronal assessment of root repair position before and after surgery, and lateral tibial tunnel technique can help anatomical repair by reducing technical error due to guide pin slip medially compared to medial tibial tunnel technique.

Objective This study was conducted to evaluate the effect of different levels of total digestible nutrients (TDN) and sodium stearoyl-2-lactylate (SSL) supplementation on growth performance and blood and carcass characteristics in Hanwoo steers during the early fattening period. Methods Sixty Hanwoo steers (average body weight, 333±36.4 kg) were randomly allotted to 3 treatments, with twenty steers per treatment, and ten steers per pen with a size of 80 m2. Dietary treatments were as follows: CON, basal diet; treatment (TRT) 0.5, 0.5% down-spec of TDN with 0.1% SSL; TRT 1.0, 1.0% down-spec of TDN with 0.1% SSL. Results The results demonstrated that average daily gain and feed efficiency increased with TRT 0.5 (0.85 kg and 11.68) vs CON (0.82 kg and 11.27) or TRT 1.0 (0.78 kg and 10.74), indicating that 0.1% SSL supplementation in the feed of early fattening steers may result in a saving of 0.5% TDN. No significant differences were observed amongst all treatments (p> 0.05) for blood metabolite concentration and blood corpuscle values, which were all within the normally accepted range for healthy steers. Conclusion Our study suggests that a TDN 0.5% down spec with 0.1% SSL supplemented feed may be effective and profitable for the early fattening period of Hanwoo steers without causing adverse effects.

Objective This study was done to evaluate the effect of sodium stearoyl-2-lactylate (SSL) supplementation in a total mixed ration (TMR) on the lactation performance, blood parameters, and economic efficacy of mid-lactation Holstein cows. Methods Twenty-four cows (body weight 647±11.7 kg) were randomly divided into 4 treatment groups, with six cows per group. The dietary treatments were as follows: basal diet (CON); CON+17.5 g of top dressed SSL (treatment [TRT] 0.05); CON+35 g of SSL (TRT 0.1); and CON+70 g of SSL (TRT 0.2) per 35 kg TMR. Results The highest level of SSL supplementation (TRT 0.2) significantly improved milk yield during the second period compared to the TRT 0.05 group (5 to 8 wks; 33.28 vs 31.09 kg/d), during the third period compared to both the CON and TRT 0.05 groups (p

Abstract Background and aims Although it is important to analyze the hemodynamic factors related to the right ventricle (RV) after left ventricular assist device (LVAD) implantation, previous studies have focused only on the alteration of the ventricular shape and lack quantitative analysis of the various hemodynamic parameters. Therefore, we quantitatively analyzed various hemodynamic parameters related to the RV under normal, heart failure (HF), and HF incorporated with continuous flow LVAD therapy by using a computational model. Methods In this study, we combined a three-dimensional finite element electromechanical model of ventricles, which is based on human ventricular morphology captured by magnetic resonance imaging (MRI) with a lumped model of the circulatory system and continuous flow LVAD function in order to construct an integrated model of an LVAD implanted-cardiovascular system. To induce systolic dysfunction, the magnitude of the calcium transient function under HF condition was reduced to 70% of the normal value, and the time constant was reduced by 30% of the normal value. Results Under the HF condition, the left ventricular end systolic pressure decreased, the left ventricular end diastolic pressure increased, and the pressure in the right atrium (RA), RV, and pulmonary artery (PA) increased compared with the normal condition. The LVAD therapy decreased the end-systolic pressure of the LV by 41%, RA by 29%, RV by 53%, and PA by 71%, but increased the right ventricular ejection fraction by 52% and cardiac output by 40%, while the stroke work was reduced by 67% compared with the HF condition without LVAD. The end-systolic ventricular tension and strain decreased with the LVAD treatment. Conclusion LVAD enhances CO and mechanical unloading of the LV as well as those of the RV and prevents pulmonary hypertension which can be induced by HF.

When steam is used in fluid machinery, phase transition can occur that affects not only the flow fields but also machine performance. Therefore, to achieve an accurate prediction of steam condensing flow using computational fluid dynamics (CFD), phase-transition phenomena should be considered and a non-equilibrium wet-steam model is required. Such a model is implemented in this study using the in-house code T-Flow, and the flow fields – including phase-transition phenomena – in various Laval nozzles are examined. The results for multi-phase flows can be obtained in relatively short time by using mixture assumption and an inner-iteration method. The calculated results reflect the characteristics of the condensing flows well and are comparable with those obtained experimentally. Also, it was found that the superheating level of incoming steam can explain the tendency of condensation in the nozzles considered in a simple way. In addition, steam condensing flows in the blade cascades were simulated. As a result, the predicted blade loading agreed well with the experimental data and the superheating level at inlet was responsible for the condensation trend not only in the nozzles but also in the cascades. In future work, the characteristics of steam condensing flow in a steam turbine where complex flows and phase transition occur can be investigated using the presented model.

To improve the dissolution behavior of telmisartan (TMS), a poorly water-soluble angiotensin II receptor blocker, TMS-phospholipid complex (TPC) was prepared by solvent evaporation method and characterized by differential scanning calorimetry and powder X-ray diffractometry. The crystalline structure of TMS was transited into an amorphous state by TPC formation. The equilibrium solubility of TPC (1.3-6.1 mg/mL) in various vehicles was about 100 times higher than that of TMS (0.009-0.058 mg/mL). TPC-loaded self-microemulsifying drug delivery system (SMEDDS) formulation was optimized using the D-optimal mixture design with the composition of 14% Capryol 90 (oil; X1), 59.9% tween 80 (surfactant; X2), and 26.1% tetraglycol (cosurfactant; X3) as independent variables, which resulted in a droplet size of 22.17 nm (Y1), TMS solubilization of 4.06 mg/mL (Y2), and 99.4% drug release in 15 min (Y3) as response factors. The desirability function value was 0.854, indicating the reliability and accuracy of optimization; in addition, good agreement was found between the model prediction and experimental values of Y1, Y2, and Y3. Dissolution of raw TMS was poor and pH-dependent, where it had extremely low dissolution (< 1% for 2 h) in water, pH 4, and pH 6.8 media; however, it showed fast and high dissolution (> 90% in 5 min) in pH 1.2 medium. In contrast, the dissolution of the optimized TPC-loaded SMEDDS was pH-independent and reached over 90% within 5 min in all the media tested. Thus, we suggested that phospholipid complex formation and SMEDDS formulation using the experimental design method might be a promising approach to enhance the dissolution of poorly soluble drugs.

Background. Although many surgical strategies have been used to reduce the anastomotic leak (AL) rate after laparoscopic rectal cancer surgery, limited data are available on the risk factors for AL and the effective strategy to reduce AL. Methods. The present study enrolled 736 consecutive patients who underwent laparoscopic resection without a diverting stoma for rectal adenocarcinoma. A nomogram was constructed to predict AL. Based on the nomogram, personalized risk was calculated and sequential surgical strategies were monitored using risk-adjusted cumulative sum (RA-CUSUM) analysis. Results. Among the 736 patients, clinical AL occurred in 65 patients (8.8%). Sex, an American Society of Anesthesiologists score, operation time, blood transfusion, and tumor location were identified as significant predictive factors for AL. Based on these factors, a nomogram was created to predict AL, with a concordance index (C-index) of 0.753 (95% confidence interval, 0.690–0.816). A calibration plot showed good statistical performance on internal validation (bias-corrected C-index of 0.742). The RA-CUSUM curve showed that extended splenic flexure mobilization (SFM) could be the most influential strategy to reduce AL. Conclusions. Our nomogram for predicting AL after laparoscopic rectal cancer surgery might be helpful to identify the individual risk of AL. Furthermore, extended SFM might be the most appropriate strategy for reducing AL.

Background The septal cartilage is the most useful donor site for autologous cartilage graft material in rhinoplasty. For successful nasal surgery, it is necessary to understand the developmental process of the nasal septum and to predict the amount of harvestable septal cartilage before surgery. Methods One hundred twenty-three Korean patients who underwent three-dimensional (3D) facial bone computed tomography (CT) were selected for evaluation of the midsagittal view of the nasal septum. Multiple parameters such as the area of each component of the nasal septum and the amount of harvestable septal cartilage were measured using Digimizer software. Results The area of the total nasal septum showed rapid growth until the teenage years, but thereafter no significant change throughout the lifetime. However, the development of the septal cartilage showed a gradual decline due to ossification changes with aging after puberty in spite of a lack of change in the total septal area. The area of harvestable septal cartilage in young adults was 549.84±151.26 mm2 and decreased thereafter with age. Conclusions A 3D facial bone CT scan can provide valuable information on the septal cartilage graft before rhinoplasty. Considering the developmental process of the septal cartilage identified in this study, septal surgery should not be performed until puberty due to the risk of nasal growth impairment. Furthermore, in elderly patients who show a decreased cartilage area due to ossification changes, septal cartilage harvesting should be performed carefully due to the risk of saddle nose deformity.

To improve the dissolution and oral bioavailability of valsartan (VST), we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMED) composed of Capmul® MCM (oil), Tween® 80 (surfactant), Transcutol® P (cosurfactant), and Poloxamer 407 (precipitation inhibitor) but encountered a stability problem (Transcutol® P-induced weight loss in storage) after solidification. In the present study, replacing Transcutol® P with Gelucire® 44/14 resulted in a novel SuSMED formulation, wherein the total amount of surfactant/cosurfactant was less than that of the previous formulation. Solidified SuSMED (S-SuSMED) granules were prepared by blending VST-containing SuSMED with selective solid carriers, L-HPC and Florite® PS-10, wherein VST existed in an amorphous state. S-SuSMED tablets fabricated by direct compression with additional excipients were sufficiently stable in terms of drug content and impurity changes after 6 months of storage at accelerated conditions (40 ± 2 °C and 75 ± 5% relative humidity). Consequently, enhanced dissolution was obtained (pH 1.2, 2 h): 6-fold for S-SuSMED granules against raw VST; 2.3-fold for S-SuSMED tablets against Diovan® (reference tablet). S-SuSMED tablets increased oral bioavailability in rats (10 mg/kg VST dose): approximately 177⁻198% versus raw VST and Diovan®. Therefore, VST-loaded S-SuSMED formulations might be good candidates for practical development in the pharmaceutical industry.

As a platform for hepsin-specific drug delivery, we previously prepared IPLVVPLRRRRRRRRC peptide (RIPL)-conjugated nanostructured lipid carriers (RIPL-NLCs) composed of Labrafil® M 1944 CS (liquid oil) and Precirol® ATO 5 (solid lipid). In this study, to prevent the recognition by the mononuclear phagocyte system, polyethylene glycol (PEG)-modified RIPL-NLCs (PEG-RIPL-NLCs) were prepared using PEG3000 at different grafting ratios (1, 5, and 10 mole %). All prepared NLCs showed a homogeneous dispersion (130⁻280 nm), with zeta potentials varying from −18 to 10 mV. Docetaxel (DTX) was successfully encapsulated in NLCs: encapsulation efficiency (93⁻95%); drug-loading capacity (102⁻109 µg/mg). PEG-RIPL-NLCs with a grafting ratio of 5% PEG or higher showed significantly reduced protein adsorption and macrophage phagocytosis. The uptake of PEG(5%)-RIPL-NLCs by cancer cell lines was somewhat lower than that of RIPL-NLCs because of the PEG-induced steric hindrance; however, the uptake level of PEG-RIPL-NLCs was still greater than that of plain NLCs. In vivo biodistribution was evaluated after tail vein injection of NLCs to normal mice. Compared to RIPL-NLCs, PEG(5%)-RIPL-NLCs showed lower accumulation in the liver, spleen, and lung. In conclusion, we found that PEG(5%)-RIPL-NLCs could be a promising nanocarrier for selective drug targeting with a high payload of poorly water-soluble drugs.