Chuna Manual Therapy or Electroacupuncture with Pregabalin for Chemotherapy-Induced Peripheral Neuropathy: A Randomized Controlled Pilot Study.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of chemotherapy, and effective treatments for CIPN are still lacking. For this reason, there is a growing interest in complementary and alternative medicine as a potential source of nonsurgical treatments for CIPN symptoms alongside pregabalin. One such option being explored is Chuna manual therapy (CMT), a traditional Korean manual therapy. Methods: This study compares the effectiveness and safety of using only pregabalin (PG) as a conventional method of treating breast and colorectal cancer patients with CIPN symptoms with a combination of both PG and electroacupuncture (EA) or CMT, while also assessing the feasibility of future large-scale clinical studies. Due to the COVID-19 pandemic, only 74 CIPN patients were recruited to this study. Twenty-five were assigned to the PG group, 26 to the PG + EA group, and 22 to the PG + CMT group for a five-week treatment and a four-week follow-up study. Results: For the primary outcome, we evaluated the mean differences in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) compared to the baseline at week 5 (visit 4). Although we found that the PG + CMT group showed the biggest difference (-16.64 [95% CI: -25.16, -8.11]) compared to the PG group (-8.60 [95% CI: -14.93, -2.27]) and the PG + EA group (-6.73 [95% CI: -12.34, -1.13]), this finding lacked statistical significance (p = 0.2075). In terms of safety, two patients in the PG + CMT group reported side effects: one bruise and one headache. Conclusions: The low attrition and high adherence rates of all the groups, and the similar rates of side effects among them, support the feasibility of larger-scale follow-up studies.

Machine Learning Approach Using Routine Immediate Postoperative Laboratory Values for Predicting Postoperative Mortality.

BACKGROUND: Several prediction models have been proposed for preoperative risk stratification for mortality. However, few studies have investigated postoperative risk factors, which have a significant influence on survival after surgery. This study aimed to develop prediction models using routine immediate postoperative laboratory values for predicting postoperative mortality. METHODS: Two tertiary hospital databases were used in this research: one for model development and another for external validation of the resulting models. The following algorithms were utilized for model development: LASSO logistic regression, random forest, deep neural network, and XGBoost. We built the models on the lab values from immediate postoperative blood tests and compared them with the SASA scoring system to demonstrate their efficacy. RESULTS: There were 3817 patients who had immediate postoperative blood test values. All models trained on immediate postoperative lab values outperformed the SASA model. Furthermore, the developed random forest model had the best AUROC of 0.82 and AUPRC of 0.13, and the phosphorus level contributed the most to the random forest model. CONCLUSIONS: Machine learning models trained on routine immediate postoperative laboratory values outperformed previously published approaches in predicting 30-day postoperative mortality, indicating that they may be beneficial in identifying patients at increased risk of postoperative death.

Clinical study on concurrent use of electro-acupuncture or Chuna manual therapy with pregabalin for chemotherapy-induced peripheral neuropathy: safety and effectiveness (open-labeled, parallel, randomized controlled trial, assessor-blinded): A study protocol.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major side effects of chemotherapy. Its main symptoms are pain, paresthesia, and numbness. However, the mechanisms underlying the development of CIPN remain unclear and standard treatments have not been established. Recently, there has been a growing interest in various approaches to overcome the limitations of the existing treatments. This study aims to evaluate the efficacy and safety of the concurrent use of two complementary and alternative therapies: electroacupuncture (EA) and Chuna manual therapy (CMT), with pregabalin, which is the conventional pharmacotherapy for neuropathic pain. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded randomized controlled trial, which includes 90 patients with colorectal and breast cancer, who developed CIPN. After a 2-week preparation period, the patients are divided into three groups (pregabalin administration group, pregabalin + EA treatment group, and pregabalin + CMT treatment group), treated for approximately 5 weeks and followed-up 4 weeks after treatment. The primary outcome is assessed using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale score (version 4.0) and the secondary outcome is measured using the Quality of Life Questionnaire-CIPN 20-Item Scale (version 3.0) and the quality of life questionnaire (version 3.0) developed by the European Organisation for Research and Treatment of Cancer. Moreover, exploratory efficacy and safety evaluations will be conducted based on the chemotherapy-completion rate and nerve conduction studies.

MicroRNAs associated with microvascular invasion in hepatocellular carcinoma and their prognostic impacts in patients undergoing hepatic resection.

Although microvascular invasion (McVI) has prognostic value for patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between McVI and the aberrant expression of microRNAs (miRNAs). The present study identified the miRNAs that were selectively expressed in HCC with McVI and investigated their prognostic value. Clinical data and the miRNA expression profiles of 372 patients with HCC were extracted from The Cancer Genome Atlas database. miRNAs that were differentially expressed between patients with McVI and those without vascular invasion (VI) were identified and investigated as potential prognostic factors for HCC. The results demonstrated that McVI was a significant predictor of shortened recurrence-free survival (RFS). The 3 year RFS rate in patients with HCC accompanied by McVI was 28.2 and 49.3% in HCC without VI (P<0.001). miRNA-141/-582/-9 were upregulated, while miRNA-675 was downregulated in patients with McVI when compared with HCC patients without VI. Log2 fold-changes of miRNA-141/-582/-675/-9 were 0.80 [false discovery rate (FDR), 0.005], 0.55 (FDR, 0.045), -0.99 (FDR, 0.005) and 1.22 (FDR, <0.001), respectively. Kaplan-Meier analysis indicated that the overexpression of miR-141/-582/-9 was significantly associated with poor RFS and a poor overall survival. A text mining analysis revealed that these miRNAs were significantly associated with multifaceted hallmarks of cancer, including 'invasion and metastasis'. In conclusion, the overexpression of miRNA-141/-582/-9 was associated with McVI and a poor survival in patients undergoing hepatic resection for HCC.

Theragnosis by a miR-141-3p molecular beacon: simultaneous detection and sensitization of 5-fluorouracil resistant colorectal cancer cells through the activation of the TRIM13-associated apoptotic pathway.

We developed a molecular beacon targeting miR-141-3p, aberrantly increased in 5-fluorouracil-resistant colorectal cancer cells (R-CRCCs). It consists of a fluorophore-labeled oligonucleotide, antisense to miR-141-3p, and a quencher. It detected R-CRCCs and recovered the chemosensitivity of them to 5-fluorouracil by hybridization with miR-141-3p, which is applicable to cancer treatment.

Exosome-Mediated Ultra-Effective Direct Conversion of Human Fibroblasts into Neural Progenitor-like Cells.

Exosomes, naturally secreted nanoparticles, have been introduced as vehicles for horizontal transfer of genetic material. We induced autologous exosomes containing a cocktail of reprogramming factors ("reprosomes") to convert fibroblasts into neural progenitor cells (NPCs). The fibroblasts were treated with ultrasound and subsequently cultured in neural stem cell medium for 1 day to induce the release of reprosomes composed of reprogramming factors associated with chromatin remodeling and neural lineage-specific factors. After being treated with reprosomes, fibroblasts were converted into NPCs (rNPCs) with great efficiency via activation of chromatin remodeling, so quickly that only 5 days were required for the formation of 1500 spheroids showing an NPC-like phenotype. The rNPCs maintained self-renewal and proliferative properties for several weeks and successfully differentiated into neurons, astrocytes, and oligodendrocytes in vitro and in vivo. Reprosome-mediated cellular reprogramming is simple, safe, and efficient to produce autologous stem cells for clinical application.

An ultra-effective method of generating extramultipotent cells from human fibroblasts by ultrasound.

Multipotent cells have similar basic features of all stem cells but limitation in ability of self-renewal and differentiation compared with pluripotent cells. Here, we have developed an ultra effective, gene- and chemical-free method of generating extra multipotent (xpotent) cells which have differentiation potential more than limited cell types, by the mechanism of ultrasound-directed permeation of environmental transition-guided cellular reprogramming (Entr). Ultrasound stimulus generated a massive number of Entr-mediated xpotent (x/Entr) spheroids from human dermal fibroblasts (HDFs) 6 days after treatment. The emergence of x/Entr was first initiated by the introduction of human embryonic stem cell (ESC) environments into the HDFs to start fast cellular reprogramming including activation of stress-related kinase signaling pathways, subsequent chromatin remodeling, and expression of pluripotent-related genes via transient membrane damage caused by ultrasound-induced cavitation. And then, pluripotent markers were transported into their adjacent HDFs via direct cell-to-cell connections in order to generate xpotent clusters. The features of x/Entr cells were intermediate between pluripotency and multipotency in terms of pluripotency with three germ layer markers, multi-lineage differentiation potential, and no teratoma formation. This physical stimulus-mediated reprogramming strategy was cost-effective, simple, quick, produced significant yields, and was safe, and can therefore provide a new paradigm for clinical application.

Bioimaging of multiple piRNAs in a single breast cancer cell using molecular beacons.

Simultaneous bioimaging of piR-36026 and piR-36743 using molecular beacons successfully visualized 4 different subtypes of breast cancer.

Multiplex bioimaging of piRNA molecular pathway-regulated theragnostic effects in a single breast cancer cell using a piRNA molecular beacon.

Recently, PIWI-interacting small non-coding RNAs (piRNAs) have emerged as novel cancer biomarkers candidate because of their high expression level in various cancer types and role in the control of tumor suppressor genes. In this study, a novel breast cancer theragnostics probe based on a single system targeting the piRNA-36026 (piR-36026) molecular pathway was developed using a piR-36026 molecular beacon (MB). The piR-36026 MB successfully visualized endogenous piR-36026 biogenesis, which is highly expressed in MCF7 cells (a human breast cancer cell line), and simultaneously inhibited piR-36026-mediated cancer progression in vitro and in vivo. We discovered two tumor suppressor proteins, SERPINA1 and LRAT, that were directly regulated as endogenous piR-36026 target genes in MCF7 cells. Furthermore, multiplex bioimaging of a single MCF7 cell following treatment with piR-36026 MB clearly visualized the direct molecular interaction of piRNA-36026 with SERPINA1 or LRAT and subsequent molecular therapeutic responses including caspase-3 and PI in the nucleus.

Laparoscopic repair of parastomal and incisional hernias with a modified Sugarbaker technique.

A parastomal hernia is the most common surgical complication following stoma formation. As the field of laparoscopic surgery advances, different laparoscopic approaches to repair of parastomal hernias have been developed. Recently, the Sugarbaker technique has been reported to have lower recurrence rates compared to keyhole techniques. As far as we know, the Sugarbaker technique has not yet been performed in Korea. We herein present a case report of perhaps the first laparoscopic parastomal hernia repair with a modified Sugarbaker technique to be successfully carried out in Korea. A 79-year-old woman, who underwent an abdominoperineal resection for an adenocarcinoma of the rectum 9 years ago, presented with a large parastomal and incisional hernias, and was treated with a laparoscopic repair with a modified Sugarbaker technique. Six months after surgery, follow-up with the patient has shown no evidence of recurrence.

Impact of diabetes on oncologic outcome of colorectal cancer patients: colon vs. rectal cancer.

BACKGROUND: To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum). PATIENTS AND METHODS: This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints. RESULTS: Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00-1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11-1.92), DFS (HR: 1.45, 95% CI: 1.15-1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98-1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007). CONCLUSIONS: This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.

Safety and efficacy of the NiTi Shape Memory Compression Anastomosis Ring (CAR/ColonRing) for end-to-end compression anastomosis in anterior resection or low anterior resection.

PURPOSE: Compression anastomoses may represent an improvement over traditional hand-sewn or stapled techniques. This prospective exploratory study aimed to assess the efficacy and complication rates in patients undergoing anterior resection (AR) or low anterior resection (LAR) anastomosed with a novel end-to-end compression anastomosis ring, the ColonRing. METHODS: In all, 20 patients (13 male) undergoing AR or LAR were enrolled to be anastomosed using the NiTi Shape Memory End-to-End Compression Anastomosis Ring (NiTi Medical Technologies Ltd, Netanya, Israel). Demographic, intraoperative, and postoperative data were collected. RESULTS: Patients underwent AR (11/20) or LAR using laparoscopy (75%), robotic (10%) surgery, or an open laparotomy (15%) approach, with a median anastomotic level of 14.5 cm (range, 4-25 cm). Defunctioning loop ileostomies were formed in 6 patients for low anastomoses. Surgeons rated the ColonRing device as either easy or very easy to use. One patient developed an anastomotic leakage in the early postoperative period; there were no late postoperative complications. Mean time to passage of first flatus and commencement of oral fluids was 2.5 days and 3.2 days, respectively. Average hospital stay was 12.6 days (range, 8-23 days). Finally, the device was expelled on average 15.3 days postoperatively without difficulty. CONCLUSIONS: This is the first study reporting results in a significant number of LAR patients and the first reported experience from South Korea; it shows that the compression technique is surgically feasible, easy to use, and without significant complication rates. A large randomized controlled trial is warranted to investigate the benefits of the ColonRing over traditional stapling techniques.

Trocar site hernia after the use of 12-mm bladeless trocar in robotic colorectal surgery.

Bladeless trocar decreases accidental injuries and incisional hernia; further a closure of fascial defect is considered to be unnecessary if a 12-mm bladeless trocar is used at nonmidline. We present a case of bowel herniation after using 12-mm bladeless trocar in robotic colorectal surgery. A 67-year-old woman had rectal cancer and underwent a robot-assisted low anterior resection. The facial defect after using 12-mm bladeless trocar was closed with the routine procedure. On postoperative day 7, her hernia of the trocar site was diagnosed by an abdominal computed tomography. The herniation was reduced with laparoscopic surgery. In conclusion, a trocar site hernia can occur after using a 12-mm bladeless trocar in robotic surgery.

Colonic ischemia following surgery for sigmoid colon and rectal cancer: a study of 10 cases and a review of the literature.

PURPOSE: Colonic ischemia following colorectal surgery is an unusual and serious complication. As it has been reported that the incidence of colonic ischemia was higher after laparoscopic surgery, the aim of this report was to document the clinical features of postoperative colonic ischemia following colorectal surgery. METHODS: Among 1,201 surgeries for sigmoid colon and rectal cancer by a single surgeon from 2006 to 2010, 10 cases of postoperative colonic ischemia were retrospectively identified (0.83%). IMA high ligation was routinely made in all surgeries. The clinical findings and laboratory data of these 10 cases were evaluated. RESULTS: Of the 10 patients, 9 were male and 1 was female. The mean age was 66.9 years old. The mean BMI was 23.3. Three patients (30%) had a cardiovascular disease other than hypertension. Eight patients (80%) underwent laparoscopic surgery and two patients (20%) underwent open surgery. Intraoperative bleeding occurred in five patients (50%, mean 435 ml). The average day for occurrence of postoperative colonic ischemia was on the 5th day (range 2nd-10th day). A consistent postoperative fever was found in eight patients (80%). Mortality due to postoperative colonic ischemia was 10%. CONCLUSIONS: Postoperative colonic ischemia may be considered one of the more important complications of colorectal resection.

Prediction of surface roughness using X-ray photoelectron spectroscopy and neural networks.

A new model for controlling plasma processes was constructed by combining atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and neural networks. The applicability of XPS to modeling etch rate was also investigated, as well as the impact of dc bias inclusion. The back-propagation neural network was used to find complex relationships between XPS and AFM data. This technique was evaluated with the etching data characterized by a 2(4) full factorial experiment. Five prediction models of surface roughness were constructed and compared. The Type I model refers to the model constructed with conventional process parameters. The Type II and III models were built with XPS and XPS plus dc bias data, respectively. The remaining Type IV and V models refer to those constructed with principal component analysis (PCA) reduced-XPS and PCA reduced-XPS plus dc bias, respectively. Mode prediction performance was evaluated as a function of training factor. In predicting the surface roughness, the Type II model yielded an improved prediction of 39% with respect to the Type IV model. The improvement was also demonstrated in modeling the etch rate. These results indicate that utilizing full XPS data is more effective for improving the model prediction performance. The advantage of XPS data was more conspicuous in constructing the surface roughness model.