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BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive target for the treatment of various malignancies; however, its therapeutic potential is limited because of the frequent occurrence of tumor cell resistance. In this study, we determined whether TRAIL resistance acquired by repeated administration could be overcome by HDAC inhibition in human colorectal cancer cells. METHODS: TRAIL-resistant HCT116 human colorectal cancer cells (HCT116-TR) were generated by repeated treatment with 10 and 25 ng/mL TRAIL twice weekly for 28 days. RESULTS: The resulting TRAIL-resistant cells were noncross-resistant to other chemotherapeutic agents. The levels of histone acetylation-related proteins, such as ac-histone H4 and HDAC1, were altered in HCT116-TR cells compared with the parental HCT116 cell line. The combined treatment with TRAIL and HDAC inhibitors significantly increased apoptosis in HCT116-TR cells and indicated a synergistic effect. The mechanism by which HDAC inhibition sensitizes HCT116-TR cells to TRAIL is dependent on the intrinsic pathway. In addition, we found that HDAC inhibition enhanced the sensitivity of cells to TRAIL through mitogen-activated protein kinases/CCAAT/enhancer-binding protein homologs of protein-dependent upregulation of death receptor 5. CONCLUSION: These results suggest that histone acetylation is responsible for acquired TRAIL resistance after repeated exposure and acquired resistance to TRAIL may be overcome by combination therapies with HDAC inhibitors.
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PURPOSE: To compare high flip angle (FA) hepatobiliary-phase (hHBP) imaging with variable time intervals to conventional HBP (cHBP) to assess the impact of increased FA on image quality in shortened HBP imaging. METHODS: Data from 218 patients, divided into normal liver group (n = 184) and decompensated liver group (n = 34), who underwent liver magnetic resonance imaging (MRI) including 10-min, 15-min, 20-min hHBP, and cHBP were analyzed. Signal-to-noise ratio (SNR), contrast-ratio (CR), contrast-to-noise ratio (CNR), signal intensity ratios (SIRs), and relative enhancement (RE) of the liver were calculated for quantitative analysis. Sharpness, noise, and artifacts of the image, contrast media visibility, overall image quality, and lesion conspicuity were evaluated by two abdominal radiologists. RESULTS: Quantitative analysis showed that SNR, RE, SIR for liver/muscle, liver/spleen, and CR of all hHBP images demonstrated a significantly higher value compared to cHBP images in the normal liver group (p < 0.001). These values were also superior in the normal liver group compared to the decompensated liver group (p < 0.01). In qualitative analysis, both normal and decompensated liver groups exhibited significantly superior image sharpness in all hHBP images compared to cHBP images and the overall image quality of the 15-min and 20-min hHBP did not show significant difference compared to cHBP. All values tended to be better in the normal liver group than the decompensated liver group with statistical significance except for lesion conspicuity (p < 0.01). CONCLUSION: High-FA HBP has proven to be a valuable image acquisition method, potentially shortening liver MR imaging time while maintaining acceptable image quality.
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Meios de Contraste , Hepatopatias , Imageamento por Ressonância Magnética , Razão Sinal-Ruído , Humanos , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Hepatopatias/diagnóstico por imagem , Idoso , Adulto , Fígado/diagnóstico por imagem , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Aumento da Imagem/métodos , Artefatos , Interpretação de Imagem Assistida por Computador/métodosRESUMO
RATIONALE: Adenomatous polyposis (AP) is a genetic disorder characterized by the occurrence of numerous adenomatous polyps in the colon and rectum and can be classified into classical AP and attenuated AP (AAP). AAP is diagnosed when the number of observed adenomas is between 10 and 99. The detection of AAP is significantly increasing mainly due to the improvement of the imaging technique and application of the screening program for colorectal cancer detection. Currently, the germline variations of the APC and MUTYH genes are reported as the main cause of classical AP. However, the underlying genetic basis of AAP is not well understood. In this study, we report 2 cases of AAP with MSH6 variations. PATIENT CONCERNS: Both patients visited the hospital after multiple polyps were detected during colonoscopies conducted as part of their health checkups. DIAGNOSES: The 2 patients were diagnosed with AAP through colonoscopic examination at our hospital. INTERVENTIONS: The 2 received genetic consultation; and, for follow-up purposes, both patients agreed to be tested for an underlying genetic condition through next generation sequencing. And germline MSH6 variations were detected in both AAP patients. OUTCOMES: There was no recurrence for both patients for 3 years follow-up. LESSONS: Minor portion of AAP can cause by genetic mutation in MSH6, and further research is needed.
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Polipose Adenomatosa do Colo , Proteínas de Ligação a DNA , Humanos , Masculino , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/diagnóstico , Pessoa de Meia-Idade , Feminino , Proteínas de Ligação a DNA/genética , Adulto , Colonoscopia , Mutação em Linhagem GerminativaRESUMO
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.
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BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Estudos Multicêntricos como Assunto , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Fluoruracila/uso terapêuticoRESUMO
Purpose: Patients with obstructive colorectal cancer managed by emergency surgery show high morbidity, mortality, and stoma formation rates. Decompression modalities, including the self-expandable metallic stent (SEMS) and tube drainage (TD), have been used to improve surgical outcomes. However, there have been limited studies comparing the 2 modalities. We performed a meta-analysis on short- and long-term outcomes between SEMS and TD. Methods: PubMed, EMBASE, Cochrane Library, and Google Scholar were searched. Data were pooled, and the overall effect size was calculated using random effect models. Outcome measures were perioperative short-term and 3-year survival outcomes. Results: We included 20 nonrandomized studies that examined 2,047 patients in the meta-analysis. The meta-analysis showed SEMS had better short-term outcomes in clinical success rate, decompression-related complications, laparoscopic surgery rate, stoma formation rate, and postoperative complication rate with a relative risk (RR) of 0.36 (95% confidence interval [CI], 0.24-0.54; I2 = 20%), 0.32 (95% CI, 0.20-0.50; I2 = 0%), 0.47 (95% CI, 0.34-0.66; I2 = 87%), 0.34 (95% CI, 0.24-0.49; I2 = 52%), and 0.70 (95% CI, 0.54-0.89, I2 = 28%), respectively. However, there was no significant difference between the 2 groups in 3-year overall survival (RR, 0.99; 95% CI, 0.77-1.27; I2 = 0%). Conclusion: Although the long-term oncologic impact of SEMS is still unclear compared with TD, the results of this meta-analysis may suggest that SEMS insertion can be performed more successfully and safely and may have benefits for short-term perioperative outcomes compared with TD. Further studies are warranted to provide more definitive survival results.
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Gastric cancer (GC) persists as the fourth most prevalent cause of global cancer-related mortality, presenting a challenge due to the scarcity of available therapeutic strategies. Precision medicine is crucial not only in the treatment but also in the management of GC. We performed gene panel sequencing with Oncomine focus assay comprising 52 cancer-associated genes and MSI analysis in 100 case-matched gastric cancer cases. A comprehensive analysis of clinical and genetic characteristics was conducted on these genetic results and clinicopathological findings. Upon comparison of clinicopathological characteristics, significant differences between early gastric cancer (EGC) and advanced gastric cancer (AGC) were observed in tumor location (p = 0.003), Lauren classification (p = 0.015), T stage (p = 0.000), and N stage (p = 0.015). The six most frequently mutated genes were PIK3CA (29%, 10/35), ERBB2 (17%, 6/35), KRAS (14%, 5/35), ALK (6%, 2/35), ESR1 (6%, 2/35), and FGFR3 (6%, 2/35). Regarding genetic variation, there was a tendency for the N stage to be higher in GC patients with mutated genes (p = 0.014). The frequency of mutations in GC patients was statistically significantly higher in AGC (n = 24) compared to EGC (n = 11) (odds ratio, 2.792; 95% confidence interval, 1.113 to 7.007; p = 0.026). Six of the ten GC patients carrying mutated genes and exhibiting MSI were classified into intestinal-type and undifferentiated GC, with the location of the tumor being in the lower-third. Among these patients, five harbored mutated PIK3CA, while the remaining patient had a mutation in ALK. Conclusions: AGC patients more frequently exhibited alterations of PIK3CA, KRAS, and ERBB2 as somatic oncogenic drivers, and displayed a higher prevalence of cumulative genetic events, including increased rates of PIK3CA mutations, enhanced detection of immunotherapy biomarkers, and mutations of the ESR1 gene.
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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.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Terapia Neoadjuvante/métodos , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fluoruracila/uso terapêutico , Neoplasias Retais/radioterapia , Neoplasias Retais/tratamento farmacológico , Quimiorradioterapia/métodos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: The distinction between D3 lymph nodes and actual lymphatic pathways in primary tumors can be difficult during surgery, making it challenging to confirm the completeness of D3 lymph node dissection. Fluorescence lymph node mapping (FLNM) is a promising method for lymph node visualization. PURPOSE: This study aimed to assess whether FLNM enhances the effectiveness of D3 lymph node dissection in patients with right-sided colon cancer. METHODS: Endoscopic submucosal indocyanine green injection were performed on the distal margin of the colon cancer. In an FLNM group, the lymphatic drainage pathway and distribution of D3 lymph nodes were explored. Pathological evaluations were conducted for the fluorescent D3 and non-fluorescent D3 lymph nodes. RESULTS: The FLNM group showed a significantly higher number of harvested lymph nodes in the D3 area. In stage III patients, the proportion of D3 lymph node metastasis was significantly higher in the FLNM group. The harvested D3 lymph node count showed a proportional correlation with a metastatic lymph node count of up to 15. CONCLUSION: FLNM could be considered a promising new strategy to potentially increase harvested D3 lymph node counts in colon cancer surgery.
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BACKGROUND: Incisional hernia following abdominal surgery is a frequent complication of midline laparotomy. This complication is strongly associated with the technique and material used for suture. While a monofilament absorbable suture is recommended to prevent incisional hernia, it can lead to suture loosening or surgical-knot breakage. Although barbed sutures can be an alternative suture material in abdominal fascial closure, evidence for its safety and effectiveness is lacking. Therefore, we designed a prospective randomized trial to evaluate the safety and efficacy of absorbable barbed sutures for midline fascia closure in minimally invasive surgery for colorectal and gastric cancers in comparison with conventional absorbable monofilament sutures. METHODS: A total of 312 patients who underwent minimally invasive surgery for colorectal and gastric cancers will be randomly allocated to either the absorbable barbed or monofilament suture group for abdominal fascia closure in a 1:1 ratio. The primary outcome is incisional hernia rate within 3 years after surgery, as verified by physical examination and computed tomography. Postoperative complications, including surgical site infection, postoperative pain, and quality of life, will be compared between two groups as secondary outcomes. The investigator will examine the patients until discharge and at 6, 12, 18, 24, and 36 months postoperatively. DISCUSSION: This is the first randomized controlled trial to compare absorbable barbed sutures with monofilament sutures for midline fascia closure in minimally invasive surgery. If absorbable barbed sutures demonstrate superior results to those of monofilament sutures, this type of suture material may be recommended as an alternative option for abdominal fascia closure. TRIAL REGISTRATION: KCT0007069. Registered on January 30, 2023.
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Técnicas de Fechamento de Ferimentos Abdominais , Neoplasias Colorretais , Hérnia Incisional , Neoplasias Gástricas , Humanos , Hérnia Incisional/etiologia , Hérnia Incisional/prevenção & controle , Qualidade de Vida , Estudos Prospectivos , Neoplasias Gástricas/cirurgia , Técnicas de Sutura/efeitos adversos , Técnicas de Fechamento de Ferimentos Abdominais/efeitos adversos , Fáscia , Procedimentos Cirúrgicos Minimamente Invasivos , Suturas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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 < 0.05 (two-sided testing). DISCUSSION: This trial may show that the non-muscle-cutting periumbilical transverse incision will reduce the incidence of incisional hernias compared to the midline incision. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) of Republic of Korea, KCT0006082 . Registered on April 12, 2021.
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Neoplasias do Colo , Hérnia Incisional , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/prevenção & controle , Neoplasias do Colo/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Imagem Corporal , Inquéritos Epidemiológicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
PURPOSE: Renin-angiotensin system (RAS) is involved in the pathophysiology of colonic inflammation. The aim of this study was to investigate whether small angiotensins (Angs) peptides play a role in the regulation of colonic motility and their roles are modulated in colitis. METHODS: Experimental colitis was induced by an intake of 5% dextran sulfate sodium (DSS) dissolved in tap water for 7 days in Sprague-Dawley rats. After sacrifice, plasma hormone concentrations and messenger RNAs (mRNAs) for RAS were measured. Functional analysis of colonic motility in response to Angs peptides was performed using Taenia coli. RESULTS: DSS-treated colon showed an increased necrosis with massive infiltration of inflammatory cells. The mRNA level of colonic angiotensin II receptor type 2 (AT2R) in DSS-treated rats was higher than that in control rats whereas the mRNA levels of angiotensin II converting enzyme (ACE), ACE2, AT1R, AT4R, and Mars receptor were not different from those in control rats. Ang III, Ang IV, and Ang-(1-9) (1, 3 µM) increased the frequency of basal colonic motility. Ang-(1-7) did not cause any significant changes in frequency and amplitude of basal motility. The order of potency for an increased frequency of basal motility seems to be Ang II>>Ang IV>Ang III=Ang-(1-9). The increased frequency of basal motility by Ang-(1-9) but not Ang IV was significantly enhanced in DSS-treated rat colon. CONCLUSION: In conclusion, these data suggest that small Angs peptides are partly involved in the pathophysiological regulation of colonic motility in experimental colitis.
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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.
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Fístula Anastomótica , Neoplasias Retais , Humanos , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Ligadura/métodos , Artéria Mesentérica Inferior/cirurgia , Artéria Mesentérica Inferior/patologia , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/cirurgia , Neoplasias Retais/patologiaRESUMO
BACKGROUND: Post-polypectomy electrocoagulation syndrome (PPES) can occur after colonoscopic polypectomy and is usually treated conservatively with a positive prognosis. Nevertheless, there can be cases with complications developing. CASE SUMMARY: A 58-year-old woman, who had no previous medical history, visited the Emergency Department of another hospital with symptoms of abdominal pain and fever, 1 d after multiple colonoscopic polypectomies. An abdominopelvic computed tomography (CT) scan demonstrated colo-colonic intussusception, and she was transferred to our hospital to consider an operation. CT showed colo-colonic intussusception with PPES and no evidence of obstruction. The physical examination showed localized mild tenderness on the right sided abdomen. The patient fasted and was admitted for treatment with intravenous antibiotics (piperacillin/tazobactam 4.5 g each 8 h, ornidazole 500 mg each 12 h). After admission, the symptoms got better and a follow-up CT scan demonstrated resolution of the PPES and intussusception. The patient was discharged on hospital day 9. CONCLUSION: Colo-colic intussusception can occur with PPES, and it can be properly treated conservatively.
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In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational status of TP53. Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and variational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients.
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Neoplasias Colorretais , Genes p53 , Neoplasias Colorretais/genética , Humanos , Imuno-Histoquímica , Mutação , Prognóstico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
PURPOSE: The presence of tumor deposits (TDs) in colorectal cancer is associated with a poor prognosis. In patients with the concomitant presence of both TDs and lymph nodes (LNs), there is no staging option except for the number of positive LNs alone. Therefore, to determine the prognostic value of TDs in patients with stage III colorectal cancer, meta-analyses of survival outcomes of patients with TDs were performed comparing different subgroups based on the lymph node status. METHODS: PubMed, EMBASE, and the Cochrane Library were searched. Data were pooled, and overall effect size was calculated using random-effect models. Outcome measures were 5-year overall survival (OS) and 5-year disease-free survival (DFS). RESULTS: We included in the analysis 18 nonrandomized studies and 1 prospective study that examined 90,455 patients. N1c patients (TD + LN-) had worse 5-year DFS than TDs-negative stage III patients (TD-LN +) with a RR of 1.30 (95% CI 1.06-1.61, I2 = 47%). In subgroup analysis, N1c patients had worse 5-year DFS (RR = 1.60, 95% CI = 1.25-2.05, I2 = 40%) compared with TDs-negative N1 patients (TD-N1) whereas N1c patients had better 5-year OS (RR = 0.72, 95% CI = 0.62-0.83, I2 = 0%) and 5-year DFS (RR = 0.75, 95% CI = 0.57-0.99, I2 = 0%) compared with TDs-negative N2 patients (TD-N2). CONCLUSIONS: These results may suggest that current nodal staging for colorectal cancer needs modification. The presence of TDs may have more adverse oncologic outcomes than TDs-negative N1 patients. More studies are warranted to further verify these results.
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Neoplasias Colorretais , Extensão Extranodal , Neoplasias Colorretais/patologia , Humanos , Linfonodos/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Transanal total mesorectal excision (TaTME) appears to have favorable surgical and pathological outcomes. However, the evidence on survival outcomes remains unclear. We performed a meta-analysis to compare long-term oncologic outcomes of TaTME with transabdominal TME for rectal cancer. METHODS: PubMed, EMBASE, and the Cochrane Library were searched. Data were pooled, and overall effect size was calculated using random-effects models. Outcome measures were overall survival (OS), disease-free survival (DFS), and local and distant recurrence. RESULTS: We included 11 nonrandomized studies that examined 2,143 patients for the meta-analysis. There were no significant differences between the two groups in OS, DFS, and local and distant recurrence with a RR of 0.65 (95% CI 0.39-1.09, I2 = 0%), 0.79 (95% CI 0.57-1.10, I2 = 0%), 1.14 (95% CI 0.44-2.91, I2 = 66%), and 0.75 (95% CI 0.40-1.41, I2 = 0%), respectively. CONCLUSION: In terms of long-term oncologic outcomes, TaTME may be an alternative to transabdominal TME in patients with rectal cancer. Well-designed randomized trials are warranted to further verify these results.
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Laparoscopia , Neoplasias Retais , Cirurgia Endoscópica Transanal , Humanos , Laparoscopia/métodos , Complicações Pós-Operatórias/cirurgia , Neoplasias Retais/patologia , Reto/cirurgia , Cirurgia Endoscópica Transanal/métodos , Resultado do TratamentoRESUMO
BACKGROUND: The prognostic significance of PIK3CA mutations in colorectal cancer (CRC) remains controversial. Recently, an association between programmed death ligand-1 (PD-L1) and PIK3CA mutations has been reported. The study presented here was conducted to investigate the effect of PIK3CA mutations on the prognosis of CRC patients and the association between PIK3CA mutations and PD-L1. METHODS: PIK3CA mutations were analyzed by targeted next-generation sequencing using formalin-fixed paraffin-embedded specimens from 224 primary CRC patients. PD-L1 expression was evaluated by immunohistochemical staining. RESULTS: PIK3CA mutations and PD-L1 expression were detected in 21.4% and 10.3% of CRC patients, respectively. PIK3CA mutations were significantly correlated with right-side colon cancer (P=0.011) and were correlated inversely with lymph node metastasis (P=0.026), distant metastasis (P=0.047), and high TNM stage (P=0.036). In univariate analysis, PIK3CA mutations were correlated with longer relapse-free survival in CRC patients. PD-L1 expression was correlated significantly with PIK3CA mutations (P<0.001). CONCLUSIONS: PIK3CA mutations were associated with favorable prognostic factors, longer relapse-free survival, and expression of PD-L1. Further investigation is needed to identify whether PIK3CA mutations are a good prognostic factor. Additionally, further studies are needed to understand the mechanisms behind the correlation between PIK3CA mutations and PD-L1 expression.
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Indocyanine green (ICG) could be applied for multiple functions such as fluorescent tumor localization, fluorescence lymph node mapping (FLNM), and intraoperative angiography in colorectal cancer surgery. With the near-infrared (NIR) systems, colonoscopic ICG tattooing can be used to define the early colorectal cancer that cannot be easily distinguished through the serosal surface. The lymphatic pathways can be visualized under the NIR system when ICG is injected through the submucosal or subserosal layer around the tumor. Intraoperative ICG angiography can be applied to find a favorable perfusion segment before the colon transection. Although all fluorescence functions are considered essential steps in image-guided surgery, it is difficult to perform multifunctional ICG applications in a single surgical procedure at once because complex protocols could interfere with each other. Therefore, we review the multifunctional ICG applications for fluorescent tumor localization, FLNM, and ICG angiography. We also discuss the optimal protocol for fluorescence-guided colorectal surgery.
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Rare cases of Fournier gangrene (FG) possibly associated with sodium-glucose cotransporter 2 inhibitors have been reported. We present a case of a 66-year-old male patient with type 2 diabetes mellitus on oral metformin, glimepiride, and dapagliflozin therapy. He presented with pain in the perineum and scrotum for 5 days. The clinical finding, computed tomography finding, and laboratory data were matched with FG. Emergency surgical drainage, debridement of necrotic tissue, and diverting loop ileostomy formation were performed by a urologist and a surgeon. The patient had no complications from diabetes before the onset of FG, and serum glucose management was good at the onset of FG. This case shows an FG patient with good glucose management taking dapagliflozin and suggests a possible association between dapagliflozin and FG. Further evaluation and additional research on this relationship are needed.