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1.
Surg Oncol ; 53: 102063, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38492530

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is the third most common type of cancer worldwide, and distant metastasis is frequently noted at diagnosis or follow-up. Notably, some patients with CRC can present with distant organ metastasis without any nodal involvement, which was defined as direct distant organ metastasis (DDOM). In this study, we evaluated the prognostic significance of DDOM for patients with CRC. METHODS: This study included 325 patients who had undergone primary colorectal cancer resection between August 2008 and December 2021. The patients with and without DDOM were compared (Kaplan-Meier analysis) in terms of overall survival (OS) and time to recurrence. Furthermore, the patients' clinicopathological risk factors and protective factors were analyzed (multivariate Cox proportional hazards model). RESULTS: Of the 325 patients, 65 (20%) had DDOM (Direct+ group) and 260 (80%) did not (Direct- group). The Kaplan-Meier analysis revealed that OS was significantly better in the Direct+ group than in the Direct- group (p < 0.01). A subgroup analysis by CRC stage was performed; for the patients with non-stage-IV CRC, the rate of OS was significantly higher in the Direct+ group than in the Direct- group (p = 0.02). However, DDOM did not affect the OS of the patients with stage IV CRC. The multivariate analysis indicated DDOM, left colon tumor location, and postoperative adjuvant chemotherapy were significant protective factors for disease-related mortality in the patients with non-stage-IV CRC; by contrast, body mass index, curative resection, and postoperative adjuvant chemotherapy were identified to be significant protective factors in the patients with stage IV CRC. CONCLUSIONS: DDOM appears to be significantly associated with improved OS in patients with non-stage-IV CRC but not in those with stage IV CRC. Furthermore, the time to cancer recurrence may not vary significantly between patients with DDOM and those without it.


Subject(s)
Colorectal Neoplasms , Humans , Prognosis , Colorectal Neoplasms/pathology , Retrospective Studies , Neoplasm Staging , Proportional Hazards Models
2.
BMC Surg ; 24(1): 66, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378522

ABSTRACT

BACKGROUND: Numerous factors can influence bowel movement recovery and anastomotic healing in colorectal surgery, and poor healing can lead to severe complications and increased medical expenses. Collagen patch cover (CPC) is a promising biomaterial that has been demonstrated to be safe in animal models and has been successfully applied in various surgical procedures in humans. This study. METHODS: A retrospective review of medical records from July 2020 to June 2022 was conducted to identify consecutive patients who underwent laparoscopic colectomy. Patients who received CPC at the anastomotic site were assigned to the collagen group, whereas those who did not receive CPC were assigned to the control group. RESULTS: Data from 241 patients (collagen group, 109; control group, 132) were analyzed. Relative to the control group, the collagen group exhibited a faster recovery of bowel function, including an earlier onset of first flatus (2.93 days vs. 3.43 days, p < 0.01), first defecation (3.73 days vs. 4.18 days, p = 0.01), and oral intake (4.30 days vs. 4.68 days, p = 0.04). CPC use was also associated with lower use of postoperative intravenous analgesics. The complication rates in the two groups did not differ significantly. CONCLUSIONS: CPCs can be safely and easily applied to the anastomotic site during laparoscopic colectomy, and can accelerate bowel movement recovery. Further studies on the effectiveness of CPCs in colorectal surgery involving larger sample sizes are required. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT05831956 (26/04/2023).


Subject(s)
Defecation , Laparoscopy , Humans , Colectomy/methods , Collagen/therapeutic use , Laparoscopy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Recovery of Function , Retrospective Studies , Treatment Outcome
3.
Aging (Albany NY) ; 16(2): 1620-1639, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38244581

ABSTRACT

BACKGROUND: The tumor microenvironment (TME) plays a vital role in tumor progression through intricate molecular interactions. Cancer-associated fibroblasts (CAFs), notably those expressing alpha-smooth muscle actin (α-SMA) or myofibroblasts, are instrumental in this context and correlate with unfavorable outcomes in colorectal cancer (CRC). While several transcription factors influence TME, the exact regulator causing CAF dysregulation in CRC remains elusive. Prospero Homeobox 1 (PROX1) stands out, as its inhibition reduces α-SMA-rich CAF activity. However, the therapeutic role of PROX1 is debated due to inconsistent study findings. METHODS: Using the ULCAN portal, we noted an elevated PROX1 level in advanced colon adenocarcinoma, linking to a poor prognosis. Assays determined the impact of PROX1 overexpression on CRC cell properties, while co-culture experiments spotlighted the PROX1-CAF relationship. Molecular expressions were validated by qRT-PCR and Western blots, with in vivo studies further solidifying the observations. RESULTS: Our study emphasized the connection between PROX1 and α-SMA in CAFs. Elevated PROX1 in CRC samples correlated with increased α-SMA in tumors. PROX1 modulation influenced the behavior of specific CRC cells, with its overexpression fostering invasiveness. Kaplan-Meier evaluations demonstrated a link between PROX1 or α-SMA and survival outcomes. Consequently, PROX1, alone or with α-SMA, emerges as a CRC prognostic marker. Co-culture and animal experiments further highlighted this relationship. CONCLUSION: PROX1 appears crucial in modulating CRC behavior and therapeutic resistance within the TME by influencing CAFs, signifying the combined PROX1/α-SMA gene as a potential CRC prognostic marker. The concept of developing inhibitors targeting this gene set emerges as a prospective therapeutic strategy. However, this study is bound by limitations, including potential challenges in clinical translation, a focused exploration on PROX1/α-SMA potentially overlooking other significant molecular contributors, and the preliminary nature of the inhibitor development proposition.


Subject(s)
Adenocarcinoma , Cancer-Associated Fibroblasts , Colonic Neoplasms , Colorectal Neoplasms , Animals , Cancer-Associated Fibroblasts/metabolism , Actins/metabolism , Colonic Neoplasms/genetics , Genes, Homeobox , Adenocarcinoma/genetics , Drug Resistance, Neoplasm , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Tumor Microenvironment/genetics , Fibroblasts/metabolism
4.
Cell Biol Int ; 48(2): 216-228, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38081783

ABSTRACT

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC) compared to other BC subtypes in clinical settings. Currently, there are no effective therapeutic strategies for TNBC treatment. Therefore, there is an urgent need to identify suitable biomarkers or therapeutic targets for TNBC patients. Thrombomodulin (TM) plays a role in cancer progression and metastasis in many different cancers. However, the role of TM in TNBC is not yet fully understood. First, silenced-TM in MDA-MB-231 cells caused an increase in proliferative and metastatic activity. In contrast, overexpression of TM in Hs578T cells caused a reduction in proliferation, invasion, and migration rate. Using RNA-seq analysis, we found that Integrin beta 3 (ITGB3) expression may be a downstream target of TM. Furthermore, we found an increase in ITGB3 levels in TM-KD cells by QPCR and western blot analysis but a decrease in ITGB3 levels in TM-overexpressing cells. We found phospho-smad2/3 levels were increased in TM-KD cells but decreased in TM-overexpressing cells. This implies that TM negatively regulates ITGB3 levels through the activation of the smad2/3 pathway. Silencing ITGB3 in TM-KD cells caused a decrease in proliferation and migration. Finally, we found that higher ITGB3 levels were correlated with poor overall survival and relapse-free survival in patients with TNBC. Our results indicated a novel regulatory relationship between TM and ITGB3 in TNBC.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Blotting, Western , Cell Line, Tumor , Cell Movement , Cell Proliferation , Integrin beta3/genetics , Thrombomodulin/genetics , Triple Negative Breast Neoplasms/metabolism
5.
Heliyon ; 9(11): e21657, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38028006

ABSTRACT

Background: Adhesions within the abdominal cavity develop in as many as 90 % of individuals following abdominal surgery. However, the true adhesive condition of patients can only be ascertained during the second surgery. Methods: We conducted a prospective, non-randomized study to assess the anti-adhesion properties of purified starch in patients who had undergone colorectal surgery in the past and then needed a subsequent surgical intervention. Adhesion scores have been prospectively recorded in operation notes since January 2020 when patients underwent a second surgery. Patients who had received purified starch during their initial surgery constituted the purified starch group, while those who had not received anti-adhesion medical materials were the control group. The main objectives of the study were to evaluate the extent and severity of adhesions as primary outcomes, while secondary outcomes included measuring blood loss, operation time, and postoperative complications. Results: We analyzed the data of 101 patients, with 61 in the purified starch group and 40 in the control group. In multivariate analysis, adhesion severity (Odds ratio, 0.20, 95 % confidence interval 0.08-0.54, P < 0.01) and adhesion area scores (Odds ratio, 0.13, 95 % confidence interval 0.04-0.45, P < 0.01) were significantly lower in the purified starch group than in the control group. There was no significant difference in operation times, blood loss, and postoperative complications between the two groups. Conclusion: Purified starch is a safe and effective anti-adhesion material that can significantly reduce the severity and extent of adhesion after colorectal surgery.

7.
Sci Rep ; 13(1): 18010, 2023 10 21.
Article in English | MEDLINE | ID: mdl-37865694

ABSTRACT

Post-operative pain and bleeding are the main complications following hemorrhoidal surgery. This study aimed to investigate whether an absorbable gelatin sponge is a superior hemostatic and analgesic agent compared to gauze soaked in epinephrine for post-hemorrhoidal surgery care. A retrospective study was conducted using data from a single institute. Data were collected from the electronic medical record database and outpatient patient questionnaire archive. The study encompassed 143 patients who received gauze soaked in epinephrine as the hemostatic agent after hemorrhoidal surgery and 148 patients who received an absorbable gelatin sponge. Most patients underwent stapled hemorrhoidopexy, with 119 (83.2%) in epinephrine group and 118 (79.7%) in gelatin sponge group. The primary outcome measurements were postoperative pain score, oral analgesic dosage and complications. Patients in the absorbable gelatin sponge group reported significantly lower pain scores from 8 h after their hemorrhoidal surgery (postoperative day 0) through postoperative day 2. The average pain scores in the absorbable gelatin sponge group and gauze soaked in epinephrine group were 5.3 ± 3.2 and 6.2 ± 3.2 (p = 0.03) on postoperative 8 h; 4.7 ± 3.0 and 5.8 ± 2.9 (p ≤ 0.01) on postoperative day one; and 4.4 ± 2.8 and 5.3 ± 2.9 (p = 0.01) on postoperative day two, respectively. There were no significant differences in postoperative recovery or complication rates between the two groups. Our study revealed that absorbable gelatin sponges provide more effective pain relief to patients during the initial postoperative days after hemorrhoidal surgery, without any adverse impact on patient outcomes. Consequently, absorbable gelatin sponges are recommended as a replacement for gauze soaked in epinephrine following hemorrhoidal surgery.


Subject(s)
Gelatin , Hemostatics , Humans , Retrospective Studies , Hemostatics/therapeutic use , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Analgesics/therapeutic use , Hemostasis
8.
Int J Mol Sci ; 24(12)2023 Jun 11.
Article in English | MEDLINE | ID: mdl-37373155

ABSTRACT

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide. Even with advances in therapy, CRC mortality remains high. Therefore, there is an urgent need to develop effective therapeutics for CRC. PCTAIRE protein kinase 1 (PCTK1) is an atypical member of the cyclin-dependent kinase (CDK) family, and the function of PCTK1 in CRC is poorly understood. In this study, we found that patients with elevated PCTK1 levels had a better overall survival rate in CRC based on the TCGA dataset. Functional analysis also showed that PCTK1 suppressed cancer stemness and cell proliferation by using PCTK1 knockdown (PCTK1-KD) or knockout (PCTK1-KO) and PCTK1 overexpression (PCTK1-over) CRC cell lines. Furthermore, overexpression of PCTK1 decreased xenograft tumor growth and knockout of PCTK1 significantly increased in vivo tumor growth. Moreover, knockout of PCTK1 was observed to increase the resistance of CRC cells to both irinotecan (CPT-11) alone and in combination with 5-fluorouracil (5-FU). Additionally, the fold change of the anti-apoptotic molecules (Bcl-2 and Bcl-xL) and the proapoptotic molecules (Bax, c-PARP, p53, and c-caspase3) was reflected in the chemoresistance of PCTK1-KO CRC cells. PCTK1 signaling in the regulation of cancer progression and chemoresponse was analyzed using RNA sequencing and gene set enrichment analysis (GSEA). Furthermore, PCTK1 and Bone Morphogenetic Protein Receptor Type 1B (BMPR1B) in CRC tumors were negatively correlated in CRC patients from the Timer2.0 and cBioPortal database. We also found that BMPR1B was negatively correlated with PCTK1 in CRC cells, and BMPR1B expression was upregulated in PCTK1-KO cells and xenograft tumor tissues. Finally, BMPR1B-KD partially reversed cell proliferation, cancer stemness, and chemoresistance in PCTK1-KO cells. Moreover, the nuclear translocation of Smad1/5/8, a downstream molecule of BMPR1B, was increased in PCTK1-KO cells. Pharmacological inhibition of Smad1/5/8 also suppressed the malignant progression of CRC. Taken together, our results indicated that PCTK1 suppresses proliferation and cancer stemness and increases the chemoresponse of CRC through the BMPR1B-Smad1/5/8 signaling pathway.


Subject(s)
Colorectal Neoplasms , Drug Resistance, Neoplasm , Humans , Bone Morphogenetic Protein Receptors, Type I/metabolism , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Cyclin-Dependent Kinases/metabolism , Drug Resistance, Neoplasm/genetics , Fluorouracil/pharmacology , Gene Expression Regulation, Neoplastic , Signal Transduction
9.
Mar Drugs ; 20(8)2022 Jul 27.
Article in English | MEDLINE | ID: mdl-36005485

ABSTRACT

Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several types of cancers. A thyroxine-deaminated analogue, tetrac, binds to integrin αvß3 to induce anti-proliferation in different cancers. Heteronemin- and in combination with tetrac-induced antiproliferative effects were evaluated. Tetrac enhanced heteronemin-induced anti-proliferation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC). Heteronemin and tetrac arrested cell cycle in different phases. Combined treatment increased the cell accumulation in sub-G1 and S phases. The combined treatment also induced the inactivation of EGFR signaling and downregulated the phosphorylated ERK1/2 protein in both cell lines. Heteronemin and the combination showed the downregulation of the phosphorylated and total PI3K protein in HT-29 cells (KRAS WT CRC). Results by NanoString technology and RT-qPCR revealed that heteronemin and combined treatment suppressed the expression of EGFR and downstream genes in HCT-116 cells (KRAS MT CRC). Heteronemin or combined treatment downregulated genes associated with cancer progression and decreased cell motility. Heteronemin or the combined treatment suppressed PD-L1 expression in both cancer cell lines. However, only tetrac and the combined treatment inhibited PD-L1 protein accumulation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC), respectively. In summary, heteronemin induced anti-proliferation in colorectal cancer cells by blocking the EGFR-dependent signal transduction pathway. The combined treatment further enhanced the anti-proliferative effect via PD-L1 suppression. It can be an alternative strategy to suppress mutant KRAS resistance for anti-EGFR therapy.


Subject(s)
Colorectal Neoplasms , Thyroxine , B7-H1 Antigen/metabolism , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/metabolism , ErbB Receptors/metabolism , Humans , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Proto-Oncogene Proteins p21(ras)/pharmacology , Signal Transduction , Terpenes , Thyroxine/analogs & derivatives
10.
Sci Rep ; 12(1): 11323, 2022 07 05.
Article in English | MEDLINE | ID: mdl-35790871

ABSTRACT

The right and left side of the colon derived from the midgut and hindgut, respectively. Previous studies have reported different characteristics of right-sided colon cancer (RCC) and left-sided colon cancer (LCC), but oncological outcomes remain unclear. This study compared the outcomes of RCC and LCC. This retrospective study included 1017 patients who received curative colectomy for stage I-III colon cancer at a single institute between August 2008 and December 2019. Overall survival (OS) and time to recurrence (TTR) were analyzed as outcome measurements. No significant difference in the OS or TTR of patients with RCC and LCC were observed. In subgroup analysis, RCC was associated with shorter TTR than LCC in stage II colon cancer (HR 2.36, 95% confidence interval 1.24-4.48, p < 0.01). Multivariate analysis demonstrated that right sidedness, R1 resection, low body mass index (BMI) and adjuvant chemotherapy were independent factors for poor prognosis for stage II colon cancer. Low BMI, perineural invasion, higher T stage and N2 stage were independent factors for poor prognosis for stage III colon cancer. The results were confirmed by multivariate analysis after propensity score matching. Our study revealed that RCC was an independent risk factor for recurrence in stage II colon cancer.


Subject(s)
Carcinoma, Renal Cell , Colonic Neoplasms , Kidney Neoplasms , Colonic Neoplasms/pathology , Humans , Neoplasm Staging , Retrospective Studies
11.
Langenbecks Arch Surg ; 407(7): 3005-3012, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35729398

ABSTRACT

BACKGROUND: Hemorrhoidal surgery is a common treatment for high-grade hemorrhoids. The necessity of preoperative enema preparation (PEP) in hemorrhoidal surgery is inconclusive. This study aims to evaluate the benefit and safety of PEP in hemorrhoidal surgery. METHODS: This comparative study analyzed data from electronic medical record database and outpatient questionnaire archive. Data of patients who underwent hemorrhoidal surgery from March 2020 to February 2021 were obtained. Patients were allocated to either the PEP or non-PEP group. Primary outcome measurements were postoperative pain and oral analgesic use. Secondary outcomes were the number of days until first defecation, length of hospital stay, time to return to work, incidence of urinary retention, delayed bleeding, and local infection. RESULTS: Data of 270 consecutive patients, with 130 and 140 in the PEP and non-PEP groups, respectively, who underwent hemorrhoidal surgery were analyzed. Most patients underwent stapled hemorrhoidopexy, with 106 (81.54%) in PEP group and 113 (80.71%) in non-PEP group. The mean pain score was significantly higher in PEP than in non-PEP group at day 0 (6.21 ± 3.23 vs 5.31 ± 3.14), day 1 (5.79 ± 2.89 vs 4.68 ± 3.02), and day 2 (5.35 ± 2.86 vs 4.42 ± 2.76). No significant differences in postoperative recovery or complications rate were noted between groups. CONCLUSION: Our findings revealed that performing PEP before hemorrhoidal surgery produced no benefit when compared with not performing PEP. Typically, the procedure of PEP is inconvenient and discomforting for patients. Therefore, we suggest that it can be omitted in hemorrhoidal surgery.


Subject(s)
Hemorrhoids , Humans , Treatment Outcome , Hemorrhoids/surgery , Pain, Postoperative , Length of Stay , Enema
13.
Int J Med Sci ; 19(1): 34-46, 2022.
Article in English | MEDLINE | ID: mdl-34975297

ABSTRACT

The incidence of colorectal cancer (CRC) has increased significantly in the past decade. Early diagnosis and new therapeutics are still urgently needed for CRC in clinical practice. Human α-defensin 6 (HD6) plays a defense role against microbes in the gastrointestinal tract. However, the role and mechanism of HD6 in CRC is still unresolved. Specimens from CRC patients with higher HD6 showed better outcomes. Overexpressed HD6 in CRC cells caused a reduction of cell proliferative, migratory, and invasive ability in vitro and in vivo. HD6-overexpressed caused S phase arrest through changes in cyclin-A and B and CDK2 levels. In addition, serpine-1 may be negatively regulated by HD6 altering the translocation of c-Jun N-terminal kinases (JNK), extracellular regulated protein kinases (ERK), and p38. Higher HD6 and lower serpine-1 levels in CRC patients reflected better outcomes. Finally, we found that HD6 interacts directly with epidermal growth factor receptor (EGFR) by co-immunoprecipitated assay. EGF treatment caused an increase of the level of serpine-1 and pEGFR levels and then increased growth activity in HD6 overexpressing cells. Together, our study shows that HD6 may compete with EGF to bind to EGFR and interrupt cancer progression in CRC. We believe these findings may give new insights for HD6 in CRC therapy.


Subject(s)
Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Epidermal Growth Factor/metabolism , alpha-Defensins/metabolism , Animals , Biomarkers, Tumor , Cell Cycle Checkpoints , Cell Proliferation , Disease Models, Animal , Epidermal Growth Factor/genetics , Epithelial-Mesenchymal Transition/physiology , ErbB Receptors/genetics , ErbB Receptors/metabolism , Gene Expression , Humans , Kaplan-Meier Estimate , Mice , Neoplasm Invasiveness , Neoplasm Metastasis , Plasminogen Activator Inhibitor 1/metabolism , S Phase/physiology , Tumor Cells, Cultured , alpha-Defensins/genetics
14.
Langenbecks Arch Surg ; 407(1): 343-351, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34550464

ABSTRACT

BACKGROUND: Totally implantable venous access ports (TIVAP) have been widely used in cancer patients for many years. The early infection (within 30 days after TIVAP implantation) rate of TIVAP accounts for about one-third of all TIVAP infections, and early infection often causes port removal and affects subsequent cancer treatment. This study investigated the incidence and risk factors for early and late infection after TIVAP implantation. METHODS: From January 2013 to December 2018, all adult cancer patients who received TIVAP implantation in Taipei Medical University Shuang-Ho Hospital were reviewed. We evaluated the incidence of TIVAP-related infection, patient characteristics, and bacteriologic data. Univariable analysis and multiple logistic regression analysis were used to evaluate the risk factors of TIVAP-related infection. RESULTS: A total of 3001 TIVAPs were implanted in 2897 patients, and the median follow-up time was 424 days (range: 1-2492 days), achieving a combined total of 1,648,731 catheter days. Thirty-one patients (1.0%) had early infection and 167 (5.6%) patients had late infection. In multivariate analysis, TIVAP combined with other surgeries (p = 0.03) and inpatient setting (p < 0.001) was the risk factor of early infection, and TIVAP combined with other surgeries (p = 0.007), hematological cancer (p = 0.03), and inpatient setting (p < 0.001) was the risk factor of late infection. CONCLUSION: Inpatient TIVAP implantation and TIVAP implantation combined with other surgeries are associated with high rates of TIVAP-related early and late infections.


Subject(s)
Catheter-Related Infections , Catheterization, Central Venous , Adult , Catheter-Related Infections/epidemiology , Catheterization, Central Venous/adverse effects , Catheters, Indwelling/adverse effects , Humans , Incidence , Risk Factors
16.
Asian J Surg ; 44(5): 749-754, 2021 May.
Article in English | MEDLINE | ID: mdl-33468374

ABSTRACT

BACKGROUND: Single incision laparoscopic colectomy (SILC) and single incision robotic colectomy (SIRC) are both advanced minimally invasive operative techniques. However, studies comparing these two surgical methods have not been published. The purpose of this study is to compare and evaluate the short-term outcomes of SIRC with those of SILC. METHODS: A total of 21 consecutive patients underwent SIRC and 136 consecutive patients underwent SILC in separate institutes between January 2013 and December 2019. We used retrospective cohort matching to analyze these patients. RESULTS: Prior to matching, patients who underwent SIRC had a lower percentage of American Society of Anesthesiologists (ASA) grades III-IV (5% vs. 19%, P = 0.11) compared with patients who underwent SILC. The SIRC group revealed a higher proportion of sigmoid colon lesions and anterior resections than the SILC group (61% vs. 45%, P = 0.16). After 1:4 cohort matching, 21 patients were enrolled in the SIRC group and 84 patients were enrolled in the SILC group. No statistically significant difference in terms of operative time (SIRC: 185 ± 46 min, SILC: 208 ± 53 min; P = 0.51), estimated blood loss (SIRC: 12 ± 22 ml, SILC: 85 ± 234 ml; P = 0.12), and complications (SIRC: 4.7%, SIRC: 7.1%; P = 0.31) was observed between these groups. Length of postoperative hospital stay (SIRC: 8.3 ± 1.7 days, SILC: 9.3 ± 6.5; P = 0.10) and number of harvested lymph nodes (SIRC: 21.3 ± 10.3, SILC: 21.3 ± 9.5; P = 0.77) were also similar between the two groups. In subgroup analysis, numbers of harvested lymph node is less in SIRC than SILC (SIRC: 18.1 ± 4.7 vs. SILC: 18.9 ± 8.1, P = 0.04) in anterior resection. CONCLUSION: SIRC and SILC are safe and feasible procedures with similar surgical and pathological outcomes for right- and left-side colectomy.


Subject(s)
Laparoscopy , Robotic Surgical Procedures , Case-Control Studies , Colectomy , Humans , Length of Stay , Retrospective Studies , Treatment Outcome
17.
Cells ; 9(8)2020 08 03.
Article in English | MEDLINE | ID: mdl-32756527

ABSTRACT

The property of drug-resistance may attenuate clinical therapy in cancer cells, such as chemoresistance to gefitinib in colon cancer cells. In previous studies, overexpression of PD-L1 causes proliferation and metastasis in cancer cells; therefore, the PD-L1 pathway allows tumor cells to exert an adaptive resistance mechanism in vivo. Nano-diamino-tetrac (NDAT) has been shown to enhance the anti-proliferative effect induced by first-line chemotherapy in various types of cancer, including colorectal cancer (CRC). In this work, we attempted to explore whether NDAT could enhance the anti-proliferative effect of gefitinib in CRC and clarified the mechanism of their interaction. The MTT assay was utilized to detect a reduction in cell proliferation in four primary culture tumor cells treated with gefitinib or NDAT. The gene expression of PD-L1 and other tumor growth-related molecules were quantified by quantitative polymerase chain reaction (qPCR). Furthermore, the identification of PI3K and PD-L1 in treated CRC cells were detected by western blotting analysis. PD-L1 presentation in HCT116 xenograft tumors was characterized by specialized immunohistochemistry (IHC) and the hematoxylin and eosin stain (H&E stain). The correlations between the change in PD-L1 expression and tumorigenic characteristics were also analyzed. (3) The PD-L1 was highly expressed in Colo_160224 rather than in the other three primary CRC cells and HCT-116 cells. Moreover, the PD-L1 expression was decreased by gefitinib (1 µM and 10 µM) in two cells (Colo_150624 and 160426), but 10 µM gefitinib stimulated PD-L1 expression in gefitinib-resistant primary CRC Colo_160224 cells. Inactivated PI3K reduced PD-L1 expression and proliferation in CRC Colo_160224 cells. Gefitinib didn't inhibit PD-L1 expression and PI3K activation in gefitinib-resistant Colo_160224 cells. However, NDAT inhibited PI3K activation as well as PD-L1 accumulation in gefitinib-resistant Colo_160224 cells. The combined treatment of NDAT and gefitinib inhibited pPI3K and PD-L1 expression and cell proliferation. Additionally, NDAT reduced PD-L1 accumulation and tumor growth in the HCT116 (K-RAS mutant) xenograft experiment. (4) Gefitinib might suppress PD-L1 expression but did not inhibit proliferation through PI3K in gefitinib-resistant primary CRC cells. However, NDAT not only down-regulated PD-L1 expression via blocking PI3K activation but also inhibited cell proliferation in gefitinib-resistant CRCs.


Subject(s)
B7-H1 Antigen/genetics , Cell Proliferation/drug effects , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/drug effects , Gefitinib/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Polyglactin 910/pharmacology , Thyroxine/analogs & derivatives , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , B7-H1 Antigen/metabolism , Colorectal Neoplasms/drug therapy , Drug Resistance, Neoplasm/genetics , Gefitinib/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , HCT116 Cells , HT29 Cells , Humans , Mice , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Polyglactin 910/therapeutic use , Thyroxine/pharmacology , Thyroxine/therapeutic use , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
18.
Sci Rep ; 10(1): 5189, 2020 03 23.
Article in English | MEDLINE | ID: mdl-32251336

ABSTRACT

Stapled hemorrhoidopexy has a few advantages such as less postoperative pain and faster recovery compared with conventional hemorrhoidectomy. There are two major devices used for stapled hemorrhoidopexy, PPH stapler (Ethicon EndoSurgery) and DST stapler (Covidien). This study was conducted to investigate the postoperative outcomes among patients with grade III and IV hemorrhoids who underwent hemorrhoidopexy with either of these two devices. A total of 242 consecutive patients underwent stapled hemorrhoidopexy with either PPH stapler (110 patients) or DST stapler (132 patients) at a single center in 2017. We performed a retrospective case-control study to compare the short-term postoperative outcomes and the complications between these two groups. After matching the cases in terms of age, gender, and the grade of hemorrhoids, there were 100 patients in each group (PPH versus DST). There were no significant differences in the postoperative visual analog scale (VAS) score and analgesic usage. Among complications, the incidence of anorectal stricture was significantly higher in the DST group (p = 0.02). Evaluation of the mucosal specimen showed that the total surface area, the muscle/mucosa ratio and the surface area of the muscle were also significantly higher in the DST group (p = 0.03). Further analysis of the DST group demonstrated that patients with anorectal stricture after surgery are younger than patients without anorectal stricture, and higher muscle/mucosa ratio (p = 0.03) and a higher surface area of the muscle (p = 0.03) also measured in the surgical specimen. The two devices provide similar outcomes of postoperative recovery. Patients who underwent DST stapled hemorrhoidopexy had a higher incidence rate of stricture, larger area of muscle excision, and higher muscle/mucosa ratio in the surgical specimen. Further investigation is warranted for a better understanding of the correlation between muscle excision and anorectal stricture.


Subject(s)
Hemorrhoidectomy/instrumentation , Hemorrhoids/surgery , Surgical Staplers , Acetaminophen/therapeutic use , Anal Canal/pathology , Analgesics/therapeutic use , Anus Diseases/etiology , Constriction, Pathologic/etiology , Equipment Design , Female , Hemorrhage/etiology , Humans , Intestinal Mucosa/pathology , Isoxazoles/therapeutic use , Male , Middle Aged , Organ Size , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Postoperative Complications/etiology , Retrospective Studies , Treatment Outcome , Urinary Retention/etiology
19.
J Laparoendosc Adv Surg Tech A ; 30(2): 183-187, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31765269

ABSTRACT

Background: Single-incision laparoscopic colectomy (SILC), although it achieves better cosmetic outcomes, less pain, and faster recovery compared with multiport laparoscopic colectomy, has several limitations and technical difficulties. Herein, we report our initial experience with single-incision robotic colectomy (SIRC) compared with multiport robotic colectomy (MPRC). Materials and Methods: From January 2017 to July 2019, we identified consecutive patients who underwent robotic colectomy. According to the surgical technique, we divided the patients into two groups: SIRC and MPRC. Results: A total of 40 patients underwent robotic colectomy; 20 patients underwent each of SIRC and MPRC. There were no significant differences in baseline characteristics between the two groups. The SIRC group had less blood loss and a shorter average incision length than the MPRC group (P < .05); SIRC also used fewer robotic instruments than MPRC (P ≤ .05). Conclusions: SIRC is a safe and feasible procedure in both right- and left-sided colectomy. SIRC can reduce the total incision length and surgical cost relative to MPRC, reduce surgical instrument collision, and improve the nonergonomic surgical operating environment faced by surgeons performing SILC during surgery.


Subject(s)
Colectomy/methods , Laparoscopy/methods , Robotic Surgical Procedures/methods , Aged , Blood Loss, Surgical , Female , Humans , Length of Stay , Male , Middle Aged , Robotic Surgical Procedures/instrumentation
20.
PLoS One ; 14(1): e0210274, 2019.
Article in English | MEDLINE | ID: mdl-30657763

ABSTRACT

Advanced colorectal cancer (CRC) survival rates are still low despite advances in cytotoxic and targeted therapies. The development of new effective or alternative therapies is therefore urgently needed. Bromelain, an extract of pineapple, was shown to have anticancer effects, but its mechanisms in CRC have not been fully explored. Therefore, the roles of bromelain in CRC progression were investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model. The anticancer mechanisms were explored by assessing the role of bromelain in inducing reactive oxygen species (ROS), superoxide, autophagosomes, and lysosomes. The role of bromelain in the induction of apoptosis was also assessed. It was found that bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models. It also induced high levels of ROS and superoxide, plus autophagosome and lysosome formation. High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9 according to a qPCR analysis. In a Western blot analysis, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This study explored the role of bromelain in CRC while giving insights into its mechanisms of action. This compound can offer a cheap alternative to current therapies.


Subject(s)
Apoptosis/drug effects , Autophagy , Bromelains/pharmacology , Cell Proliferation/drug effects , Colorectal Neoplasms/pathology , Reactive Oxygen Species/metabolism , Animals , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Tumor Cells, Cultured , Xenograft Model Antitumor Assays , Zebrafish
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