Intracorporeal anastomosis in minimally invasive right hemicolectomy: a nationwide survey of the Korean Society of Coloproctology.

Purpose: We investigated the current practices and perceptions of colorectal surgeons in South Korea regarding intracorporeal ileocolic anastomosis (IIA) in minimally invasive right hemicolectomy (RHC). Methods: Members of the Korean Society of Coloproctology (KSCP) participated in an online survey encompassing demographic information, surgical experiences, methods for IIA, and advantages, barriers, and perceptions of IIA. We performed a statistical analysis of survey results. Results: Among the 1,074 KSCP members contacted, 178 responded to the survey. Most respondents were males aged 40-49 years with >10 years of experience who were affiliated with a tertiary healthcare facility. One hundred fifty-six respondents had performed <100 colorectal cancer surgeries annually. Fifty-nine respondents reported experiences of the IIA technique in minimally invasive RHC. Most respondents favored the isoperistaltic side-to-side (S-S) anastomosis and stapled S-S anastomosis, hand-sewn closure for the common channel, and the periumbilical area for primary specimen extraction. Respondents with IIA experience emphasized the reduction in postoperative complications as the primary reason for performing IIA, whereas respondents without IIA experience cited the lack of benefits as the main deterrent. Respondents commonly cited concerns regarding anastomotic leakage and intraabdominal contamination as the primary reasons for not performing IIA. Respondents with IIA experience demonstrated a more positive response towards attempting or transitioning to IIA than those without. Respondents with IIA experience prioritized self-sufficiency, whereas respondents without IIA experience prioritized proctorship and discussions of the initial cases. Conclusion: Measures to standardize the IIA technique and appropriate training programs must be implemented to enhance its use in minimally invasive RHC.

Moderating AKT signaling with baicalein protects against weight loss by preventing muscle atrophy in a cachexia model caused by CT26 colon cancer.

Cancer cachexia is a type of energy-wasting syndrome characterized by fatigue, anorexia, muscle weakness, fat loss, and systemic inflammation. Baicalein, a flavonoid with bioactive properties, has demonstrated the ability to mitigate cardiac and skeletal muscle atrophy in different experimental settings. This effect is achieved through the inhibition of muscle proteolysis, suggesting its potential in preserving skeletal muscle homeostasis. In this study, we investigated the anti-cancer cachexia effects of baicalein in the regulation of muscle and fat wasting, both in vivo and in vitro. Baicalein attenuated body weight loss, including skeletal muscle and white adipose tissue (WAT), in CT26-induced cachectic mice. Moreover, baicalein increased muscle fiber thickness and suppressed the muscle-specific ubiquitin-protease system, including F-box only protein 32 and muscle RING-finger protein-1, by activating AKT phosphorylation both in vivo and in vitro. The use of LY294002, a particular inhibitor of AKT, eliminated the observed impact of baicalein on the improvement of muscle atrophy. In conclusion, baicalein inhibits muscle proteolysis and enhances AKT phosphorylation, indicating its potential role in cancer cachexia-associated muscle atrophy.

Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): an open-label, parallel, randomized, phase 2 trial.

BACKGROUND: Cancer cachexia (CC) is a multifactorial process characterized by progressive weight loss, muscle mass, and fat tissue wasting, which adversely affects the quality of life and survival of patients with advanced stages of cancer. CC has a complex and multifactorial pathophysiology, and there is no established standard treatment. Therefore, it is often irreversible and a single treatment modality is unlikely to suppress its progression. We are conducting a randomized trial to investigate the efficacy and safety of a multimodal intervention compared to the best supportive care for patients who received palliative chemotherapy. METHODS: Patients with lung or gastrointestinal cancers undergoing palliative chemotherapy are eligible. Patients are randomized into a multimodal intervention care (MIC) arm versus a conventional palliative care (CPC) arm. MIC includes ibuprofen, omega-3-fatty acid, oral nutritional supplement, weekly physical, psychiatric assessment, nutritional counseling, and complementary and alternative medicine. CPC includes basic nutritional counseling and megestrol acetate as needed (i.e., anorexia ≥ grade 2). All interventions are performed for 12 weeks per subject. The co-primary outcomes are change (kg) in total lean body mass and handgrip strength (kg) from the baseline. A total of 112 patients will be assigned to the two arms (56 in each group). DISCUSSION: The purpose of this study is to evaluate the effect of MIC in preventing or alleviating CC in patients who underwent palliative chemotherapy. As there is no established single treatment for CC, it is expected that the results of this clinical trial will provide new insights to significantly improve the quality of life of patients with cancer. Considering the complex mechanisms of cachexia, the effect of MIC rather than a single specific drug is more promising. In this study, we did not overly restrict the type of cancer or chemotherapy. Therefore, we attempted to measure the effects of complex interventions while preserving clinical situations. Thus, it is expected that the results of this study can be applied effectively to real-world practice. TRIAL REGISTRATION: This clinical trial was registered in the Clinical Research Information Service (KCT0004967), Korean Clinical Trial Registry on April 27, 2020, and ClinicalTrial.gov (NCT04907864) on June 1, 2021.

Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples.

PURPOSE: Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC. METHODS: From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated. RESULTS: Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors. CONCLUSION: UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status.

Is Laparoscopic Complete Mesocolic Excision and Central Vascular Ligation Really Necessary for All Patients With Right-Sided Colon Cancer?

Colon cancer treatment is on the way to evolution over several decades. The minimally invasive surgery has improved postoperative short-term outcomes. Adjuvant chemotherapy has prolonged the survival of advanced colon cancer patients. Hohenberger proposed the noble concept of complete mesocolic excision (CME) which consists of 3 components: plane surgery, sufficient longitudinal bowel resection, and central vascular ligation (CVL). Mesocolic plane surgery shares the same surgical principle of total mesorectal excision, which is maintaining the intact mesothelial envelope. However, there remain debates about the extent of bowel resection and the level of CVL for maximizing lymph node dissection. There is no solid clinical evidence for the oncological necessity and benefit of extended radical dissection in right hemicolectomy. CME with CVL based on open surgery has been adopted in laparoscopic surgery. So, it is also necessary to look at how the CME could be transformed and successfully implanted in the laparoscopic era. Recent rapid advances in surgical technology and cancer biology are preparing for fundamental changes in cancer surgery. In this study, we reviewed the history, oncological necessity, and compatibility of CME for the right hemicolectomy in the laparoscopic era and outline the new perspectives on the evolution of cancer surgery.

Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model.

Cancer cachexia is a multifactorial systemic inflammation disease caused by complex interactions between the tumor and host tissues via soluble factors. However, whether cancer cachexia affects the bone marrow, in particular the hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), remains unclear. Here, we investigated the bone marrow and bone in a cancer cachexia animal model generated by transplanting Lewis lung carcinoma cells. The number of bone marrow mononuclear cells (BM-MNCs) started to significantly decrease in the cancer cachectic animal model prior to the discernable loss of muscle and fat. This decrease in BM-MNCs was associated with myeloid skewing in the circulation and the expansion of hematopoietic progenitors in the bone marrow. Bone loss occurred in the cancer cachexia animal model and accompanied the decrease in the bone marrow MSCs that play important roles in both supporting HSCs and maintaining bone homeostasis. Glucocorticoid signaling mediated the decrease in bone marrow MSCs in the cancer cachectic environment. The cancer cachexia environment also skewed the differentiation of the bone marrow MSCs toward adipogenic fate via JAK/STAT as well as glucocorticoid signaling. Our results suggest that the bone loss induced in cancer cachexia is associated with the depletion and the impaired differentiation capacity of the bone marrow MSCs.

A Proteomic Approach to Understand the Clinical Significance of Acute Myeloid Leukemia-Derived Extracellular Vesicles Reflecting Essential Characteristics of Leukemia.

Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. ELISA results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML cell-derived EVs could reflect essential leukemia biology.

Laparoscopic Surgery for Colorectal Cancer in Korea: Nationwide Data from 2013 to 2018.

PURPOSE: We report nationwide data on the current status of laparoscopic surgery for colorectal cancer (CRC) in Korea. MATERIALS AND METHODS: Nationwide data of patients who underwent surgery for CRC from 2013 to 2018 were obtained from the Health Insurance Review & Assessment Service database. Data and trends of laparoscopy use for colorectal resection over six years were examined. RESULTS: In Korea, a total of 117,320 patients underwent surgical resection for CRC from 2013 to 2018. The proportion of laparoscopic resection increased from 64.9% in 2013 to 78.5% in 2018. The rate of laparoscopic resection for colon cancer increased from 64.7% in 2013 to 77.4% in 2018. For rectal cancer, the rate of laparoscopic resection increased from 65.4% to 81.6%. Males accounted for 59.8% of all patients, but females surpassed males at over 80 years of age. The age of peak incidence was in the 60s for males and in the 70s for females. A steady increase in the number of patients undergoing surgery for CRC was observed over 80 years of age. CONCLUSION: The laparoscopic penetration rate for CRC in Korea continued to increase annually and reached 78.5% in 2018.

Comparative lipidomics of 5-Fluorouracil-sensitive and -resistant colorectal cancer cells reveals altered sphingomyelin and ceramide controlled by acid sphingomyelinase (SMPD1).

5-Fluorouracil (5-FU) is a chemotherapeutic drug widely used to treat colorectal cancer. 5-FU is known to gradually lose its efficacy in treating colorectal cancer following the acquisition of resistance. We investigated the mechanism of 5-FU resistance using comprehensive lipidomic approaches. We performed lipidomic analysis on 5-FU-resistant (DLD-1/5-FU) and -sensitive (DLD-1) colorectal cancer cells using MALDI-MS and LC-MRM-MS. In particular, sphingomyelin (SM) species were significantly up-regulated in 5-FU-resistant cells in MALDI-TOF analysis. Further, we quantified sphingolipids including SM and Ceramide (Cer) using Multiple Reaction Monitoring (MRM), as they play a vital role in drug resistance. We found that 5-FU resistance in DLD-1/5-FU colorectal cancer cells was mainly associated with SM increase and Cer decrease, which are controlled by acid sphingomyelinase (SMPD1). In addition, reduction of SMPD1 expression was confirmed by LC-MRM-MS analysis and the effect of SMPD1 in drug resistance was assessed by treating DLD-1 cells with siRNA-SMPD1. Furthermore, clinical colorectal cancer data set analysis showed that down-regulation of SMPD1 was associated with resistance to chemotherapy regimens that include 5-FU. Thus, from our study, we propose that SM/Cer and SMPD1 are new potential target molecules for therapeutic strategies to overcome 5-FU resistance.

APSIC guidelines for the prevention of surgical site infections.

Background: The Asia Pacific Society of Infection Control (APSIC) launched the APSIC Guidelines for the Prevention of Surgical Site Infections in 2018. This document describes the guidelines and recommendations for the setting prevention of surgical site infections (SSIs). It aims to highlight practical recommendations in a concise format designed to assist healthcare facilities at Asia Pacific region in achieving high standards in preoperative, perioperative and postoperative practices. Method: The guidelines were developed by an appointed workgroup comprising experts in the Asia Pacific region, following reviews of previously published guidelines and recommendations relevant to each section. Results: It recommends that healthcare facilities review specific risk factors and develop effective prevention strategies, which would be cost effective at local levels. Gaps identified are best closed using a quality improvement process. Surveillance of SSIs is recommended using accepted international methodology. The timely feedback of the data analysed would help in the monitoring of effective implementation of interventions. Conclusions: Healthcare facilities should aim for excellence in safe surgery practices. The implementation of evidence-based practices using a quality improvement process helps towards achieving effective and sustainable results.