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A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks+ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks+ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks+ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks+ E. coli was more abundant in Stages 0-I tumor tissue than in normal mucosal tissue or in Stages II-IV tumor tissue. High abundance of pks+ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3-11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8-5.1, p < 0.001) in multivariable logistic analyses. Pks+ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7-25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3-7.3, p = 0.01) compared to the pks+ E. coli-high group. Pks+ E. coli was abundant in Stages 0-I CRC and associated with CRC prognosis. These results suggest that pks+ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.
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Neoplasias Colorrectales , Policétidos , Humanos , Escherichia coli/genética , Recurrencia Local de Neoplasia , Membrana Mucosa , CarcinogénesisRESUMEN
AIM: The significance of lymphadenectomy and its indications in patients with inguinal lymph node metastasis (ILNM) of anorectal adenocarcinoma is unclear. This study aimed to clarify the surgical outcomes and prognostic factors of inguinal lymphadenectomy for ILNM. METHOD: This study included patients who underwent surgical resection for ILNM of rectal or anal canal adenocarcinoma with pathologically positive metastases between 1997 and 2011 at 20 participating centres in the Study Group for Inguinal Lymph Node Metastasis from Colorectal Cancer organized by the Japanese Society for Cancer of the Colon and Rectum. Clinicopathological characteristics and short- and long-term postoperative outcomes were retrospectively analysed. RESULTS: In total, 107 patients were included. The primary tumour was in the rectum in 57 patients (53.3%) and in the anal canal in 50 (46.7%). The median number of ILNMs was 2.34. Postoperative complications of Clavien-Dindo Grade III or higher were observed in five patients. The 5-year overall survival rate was 38.8%. Multivariate analysis identified undifferentiated histological type (P < 0.001), pathological venous invasion (P = 0.01) and pathological primary tumour depth T0-2 (P = 0.01) as independent prognostic factors for poor overall survival. CONCLUSION: The 5-year overall survival after inguinal lymph node dissection was acceptable, and it warrants consideration in more patients. Further larger-scale studies are needed in order to clarify the surgical indications.
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Adenocarcinoma , Neoplasias del Ano , Conducto Inguinal , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Neoplasias del Recto , Humanos , Masculino , Femenino , Neoplasias del Ano/cirugía , Neoplasias del Ano/patología , Neoplasias del Ano/mortalidad , Persona de Mediana Edad , Anciano , Escisión del Ganglio Linfático/métodos , Estudios Retrospectivos , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adenocarcinoma/mortalidad , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Neoplasias del Recto/mortalidad , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Resultado del Tratamiento , Adulto , Anciano de 80 o más Años , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Tasa de Supervivencia , Pronóstico , Análisis MultivarianteRESUMEN
PURPOSE: Emergency surgery (ES) for complicated appendicitis (CA) is associated with high morbidity. Interval appendectomy (IA) decreases this rate; however, nonoperative management (NOM) is not always successful. Some patients require unplanned ES due to NOM failure (IA failure: IA-F). This study aimed to verify the benefits of IA and to evaluate the risk factors for NOM failure. METHODS: Patients diagnosed with CA who underwent surgery between January 2012 and December 2021 were included in this study. We compared the surgical outcomes of the ES group with those of the IA success (IA-S) and IA-F groups. We also analyzed 14 factors that predicted NOM failure. RESULTS: Among 302 patients, the rate of severe complications (Clavien-Dindo grade ≥ III) was significantly higher in the ES group (N = 165) than in the IA-S group (N = 102). The rates were equal between the ES (N = 165) and IA-F (N = 35) groups. NOM was successful in 110 patients and failed in 27. Lack of abscesses, comorbidities, high WBC count, and free air were independent risk factors for NOM failure. CONCLUSIONS: Considering the benefits of IA and the non-inferior surgical outcomes of IA-F compared to ES, IA is a good therapeutic strategy for CA. However, in patients exhibiting four independent risk factors for NOM failure, careful monitoring of unplanned ES is necessary.
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PURPOSE: Self-expandable metallic stent (SEMS) placement is widely used as a bridge to surgery (BTS) procedure for obstructive colorectal cancer. However, evidence regarding the optimal interval between SEMS placement and elective surgery is lacking. METHODS: We retrospectively collected data from patients with BTS between January 2013 and October 2021. Inverse probability treatment-weighted propensity score analyses were used to compare short- and long-term outcomes between the short-interval (SI) and long-interval (LI) groups, using a cutoff of 20 days. RESULTS: In total, 138 patients were enrolled in this study (SI group, n = 63; LI group, n = 75). In the matched cohort, the patients' backgrounds were well balanced. The incidence of Clavien-Dindo grade ≥ II postoperative complications was not significantly different between the SI and LI groups (19.0% vs. 14.0%, P = 0.47). There were no significant differences between the SI and LI groups in the 3-year recurrence-free survival (68.0% vs. 76.4%, P = 0.73) or 3-year overall survival rates (86.0% vs. 90.6%, P = 0.72). CONCLUSIONS: A longer interval did not deteriorate the oncological outcomes. Individual perioperative management with an appropriate interval to improve the patient's condition is required to ensure safe surgery.
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PURPOSE: In this study, we aimed to investigate the oncological impact of postoperative infection in patients with malignant large bowel obstruction managed by self-expandable metallic stent placement as a bridge to surgery. METHODS: The cohort of this multicenter retrospective study comprised 129 patients with pathological stage II/III malignant large bowel obstruction who had undergone bridge to surgery. Patients were allocated to no-postoperative infection (n = 116) and postoperative infection groups (n = 13). RESULTS: The postoperative infection group had a significantly greater proportion of men, fewer harvested lymph nodes, and longer postoperative hospital stays than did the no-postoperative infection group. Self-expandable metallic stent-related variables, including clinical failure, were not associated with postoperative infection. Male sex and low body mass index were identified as risk factors for postoperative infection by multivariate logistic regression. Three-year relapse-free survival rates were 75.5% and 30.8% in the no-postoperative infection and postoperative infection groups, respectively; this difference is statistically significant. Male sex, postoperative infection, and T4 were identified as independent prognostic factors by multivariate Cox proportional hazard analysis. The postoperative infection group had a significantly higher total recurrence rate and shorter interval to recurrence than did the no-postoperative infection group. CONCLUSION: To the best of our knowledge, this is the first study to show that postoperative infection in bridge to surgery patients has a negative oncological impact. This finding indicates that further improvement in perioperative management of bridge to surgery patients is required to minimize postoperative infection and that patient-risk stratification and additional therapy would contribute to improving oncological outcomes.
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Neoplasias Colorrectales , Obstrucción Intestinal , Stents Metálicos Autoexpandibles , Humanos , Masculino , Estudios Retrospectivos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Obstrucción Intestinal/patología , Stents Metálicos Autoexpandibles/efectos adversos , Complicaciones Posoperatorias/etiología , Tasa de Supervivencia , Neoplasias Colorrectales/cirugía , Stents/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE: Extended colectomy is sometimes chosen for treatment of transverse colon cancer (TCC) because of concerns about short- and long-term outcomes. However, there is still a lack of evidence regarding the optimal surgical procedure. METHODS: We retrospectively collected and analyzed data of patients who underwent surgical treatment of pathological stage II/III TCC at four hospitals from January 2011 to June 2019. We excluded the patients with TCC located at distal transverse colon, and just evaluated and analyzed proximal and middle third TCC. Inverse probability treatment-weighted propensity score analyses was used to compare short- and long-term outcomes between patients who underwent segmental transverse colectomy (STC) and those who underwent right hemicolectomy (RHC). RESULTS: In total, 106 patients were enrolled in this study (STC group, n = 45; RHC group, n = 61). The patients' backgrounds were well balanced after matching. The incidence of major postoperative complications (Clavien-Dindo grade ≥ III) was not significantly different between the STC and RHC groups (4.5% vs. 5.6%, respectively; P = 0.53). The 3-year recurrence-free survival and overall survival rates were not significantly different between the STC and RHC groups (88.2% vs. 81.8%, P = 0.86 and 90.3% vs. 91.9%, P = 0.79, respectively). CONCLUSION: RHC has no significant benefits over STC with respect to either short- or long-term outcomes. STC with necessary lymphadenectomy could be an optimal procedure for proximal and middle TCC.
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Colon Transverso , Neoplasias del Colon , Humanos , Estudios Retrospectivos , Puntaje de Propensión , Colon Transverso/cirugía , Neoplasias del Colon/cirugía , Colectomía/efectos adversosRESUMEN
PURPOSE: To investigate a prognostic score for stage II-III colorectal cancer (CRC) based on post-CEA and pT4 levels. METHODS: Two cohorts of stage II-III CRC patients who underwent curative surgery between 2011 and 2017 were included. The prognostic score (T-CEA score) was calculated as follows: T-CEA-0, post-CEA ≤ 5 ng/mL and pT1-3; T-CEA-1, post-CEA > 5 ng/mL or pT4; T-CEA-2, post-CEA > 5 ng/mL and pT4. RESULTS: The T-CEA scores of the 587 patients were as follows: T-CEA-0 (n = 436; 74%), T-CEA-1 (n = 129; 22%), and T-CEA-2 (n = 10; 2%). The 5-year recurrence-free survival (RFS) rates of the T-CEA-0, 1, and 2 groups were 80.3%, 54.8%, and 0%, respectively (P < 0.01), and the 5-year overall survival (OS) rates were 90.9%, 74.2%, and 0%, respectively (T-CEA-0 vs T-CEA-1: P < 0.01, T-CEA-1 vs T-CEA-2: P = 0.04). Multivariate analysis revealed that an elevated T-CEA score of 1 or 2 was a significant risk factor for poor RFS (HR: 2.89, P < 0.01) and OS (HR: 2.85, P < 0.01). CONCLUSION: The T-CEA score is a reliable and convenient prognostic score for stage II-III CRC.
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Antígeno Carcinoembrionario , Neoplasias Colorrectales , Humanos , Pronóstico , Estudios Retrospectivos , Neoplasias Colorrectales/patología , Factores de RiesgoRESUMEN
AIM: The surgical treatment of inguinal lymph node (ILN) metastases secondary to anorectal adenocarcinoma remains controversial. This study aimed to clarify the surgical treatment and management of ILN metastasis according to its classification. METHODS: This retrospective, multi-centre, observational study included patients with synchronous or metachronous ILN metastases who were diagnosed with rectal or anal canal adenocarcinoma between January 1997 and December 2011. Treatment outcomes were analysed according to recurrence and prognosis. RESULTS: Among 1181 consecutively enrolled patients who received treatment for rectal or anal canal adenocarcinoma at 20 referral hospitals, 76 (6.4%) and 65 (5.5%) had synchronous and metachronous ILN metastases, respectively. Among 141 patients with ILN metastasis, differentiated carcinoma, solitary ILN metastasis and ILN dissection were identified as independent predictive factors associated with a favourable prognosis. No significant difference was found in the frequency of recurrence after ILN dissection between patients with synchronous (80.6%) or metachronous (81.0%) ILN metastases. Patients who underwent R0 resection of the primary tumour and ILN dissection had a 5-year survival rate of 41.3% after ILN dissection (34.1% and 53.1% for patients with synchronous and metachronous ILN metastases, respectively, P = 0.55). CONCLUSION: The ILN can be appropriately classified as a regional lymph node in rectal and anal canal adenocarcinoma. Moreover, aggressive ILN dissection might be effective in improving the prognosis of low rectal and anal canal adenocarcinoma with ILN metastases; thus, prophylactic ILN dissection is unnecessary.
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Adenocarcinoma , Neoplasias del Recto , Humanos , Metástasis Linfática/patología , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Canal Anal/patología , Estudios Retrospectivos , Conducto Inguinal/patología , Conducto Inguinal/cirugía , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Adenocarcinoma/patología , Escisión del Ganglio LinfáticoRESUMEN
BACKGROUND: Preoperative colonic stenting for malignant large bowel obstruction (MLBO), also called bridge to surgery (BTS), is considered a great substitute treatment for emergency resection (ER) in the left-sided colon. However, its efficacy in the right-sided colon remains controversial. This systematic review and meta-analysis aimed to compare the postoperative short-term outcomes between BTS and ER for right-sided MLBO. METHODS: A comprehensive electronic literature search throughout December 2020 was performed to identify studies comparing short-term outcomes between BTS and ER for right-side MLBO. The main outcome measures were postoperative complications and mortality rates. A meta-analysis was performed using a fixed-effect or a random-effect method to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Seven studies were included in this meta-analysis, comprising 5136 patients, of whom 1662 (32.4%) underwent BTS and 3474 (67.6%) underwent ER. This meta-analysis demonstrated that BTS resulted in reductions in postoperative complications (OR = 0.78; 95% CI: 0.66-0.92) and mortality (OR = 0.51; 95% CI: 0.28-0.92) than ER. CONCLUSION: The results of this meta-analysis indicate that BTS for right-sided MLBO confers preferable short-term outcomes as well as for left-sided. This suggests that BTS results in a reduction of postoperative complications and mortality for right-sided MLBO than ER.
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Neoplasias del Colon , Neoplasias Colorrectales , Obstrucción Intestinal , Neoplasias del Colon/complicaciones , Neoplasias Colorrectales/cirugía , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Stents/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: To examine the potential of peripheral circulating cell-free DNA(cfDNA)as a predictor of response in patients undergoing neoadjuvant chemotherapy(NAC)for advanced colon cancer. METHODS: We compared histological response, background factors, and cfDNA molecular volume changes in cT4 and cT3N+ colon cancer patients. RESULTS: Six of 11 patients responded. The patients with muc and pap histology were non-responders. There was no relationship between CEA or cfDNA levels and response. Responders showed >50% change in DNA integrity index(=cfDNA long fragment/ short fragment ratio), while non-responders showed <50% change(p=0.015). CONCLUSION: Our results suggest that the variability rate in DNA integrity index of peripheral blood cfDNA may be useful in predicting the therapeutic efficacy of colon NAC.
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Ácidos Nucleicos Libres de Células , Neoplasias del Colon , Biomarcadores , Biomarcadores de Tumor/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/cirugía , ADN , Humanos , Terapia NeoadyuvanteRESUMEN
Late-stage elderly patients have low tolerance to chemotherapy, and they have difficulties when they are treated with standard chemotherapy. We report a case of a late-stage elderly patient who had a long-term response to UFT/UZEL/bevacizumab( Bev)therapy for lung metastasis after surgery for early-stage colon cancer. He was 82-years-old and underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer at another hospital. The pathological diagnosis was pT1b, ly1, v0, N0, M0, pStage â . Six months after the surgery, a small nodule was noted in the middle lobe of the right lung. It grew five months later and was definitely diagnosed as lung metastasis. Considering his physical condition and tumor size, we opted to introduce less invasive chemotherapy instead of standard chemotherapy. UFT/UZEL/Bev was started 14 months after surgery. Although he required dose reduction due to anorexia, he safely continued the treatment with partial response (PR), which was maintained for 2 years and 6 months. While UFT/UZEL/Bev has no convincing evidence, it may be an option for vulnerable patients, especially those with non-life-threatening disease.
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Neoplasias Pulmonares , Neoplasias del Colon Sigmoide , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Humanos , Leucovorina , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Masculino , Neoplasias del Colon Sigmoide/tratamiento farmacológico , Neoplasias del Colon Sigmoide/patología , Neoplasias del Colon Sigmoide/cirugía , Tegafur , Uracilo/uso terapéuticoRESUMEN
BACKGROUND: Neoadjuvant chemotherapy to treat locally advanced rectal cancer is an effective therapeutic strategy for the prevention of local recurrence and distant organ metastasis after surgery. OBJECTIVES: To assess the prognostic significance of histopathological tumor response in rectal cancer patients undergoing neoadjuvant chemotherapy. METHODS: This study included patients with operable rectal cancer who received neoadjuvant chemotherapy using the FOLFOX regimen (5-fluorouracil, l-leucovorin, and oxaliplatin) in a hospital between February 2012 and November 2017. The main outcome measure was disease-free survival with respect to histopathological response to neoadjuvant chemotherapy in resected specimens. RESULTS: The median follow-up was 32 months. Of 48 patients treated with neoadjuvant FOLFOX, 24 (50%) were classified as responders, which included two patients with pathological complete response and 22 patients with partial response. The remaining 24 patients (50%) were classified as nonresponders. Responders had a significantly better 3-year disease-free survival than nonresponders (86% vs. 62%, p = .02). CONCLUSIONS: Patients whose surgical specimens show a pathological complete response or partial response have good oncologic outcomes.
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Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/mortalidad , Neoplasias del Recto/mortalidad , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Adulto , Anciano , Ensayos Clínicos Fase II como Asunto , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Leucovorina/administración & dosificación , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Oxaliplatino/administración & dosificación , Pronóstico , Estudios Prospectivos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: This study investigated the short- and long-term outcomes of 18- and 22-mm-diameter self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) in patients with malignant large bowel obstruction (MLBO). METHODS: Sixty-nine pathological stage II and III colorectal cancer patients who underwent BTS were included in this multi-institutional retrospective study. Patients were divided into two groups regarding the diameter of SEMS: an 18-mm group (n = 30) and a 22-mm group (n = 39). RESULTS: There was no significant difference in the clinical success rate, but both of the two re-obstructions observed occurred in the 18-mm group. The 18-mm group showed a trend toward a higher incidence of overall postoperative complications (Clavien-Dindo grading ≥ II) than the 22-mm group (33.3% vs. 10.3%, P = 0.061). The 3-year disease-free and overall survival showed no significant differences between the 18- and 22-mm groups (78.2% vs. 68.8%, P = 0.753 and 92.8% vs. 82.1%, P = 0.471, respectively). CONCLUSION: SEMS of 18 and 22 mm diameter confer statistically equivalent short- and long-term outcomes as a BTS.
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Neoplasias Colorrectales/complicaciones , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Diseño de Equipo , Obstrucción Intestinal/cirugía , Stents Metálicos Autoexpandibles , Anciano , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Incidencia , Obstrucción Intestinal/epidemiología , Obstrucción Intestinal/etiología , Obstrucción Intestinal/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Recurrencia , Estudios Retrospectivos , Stents Metálicos Autoexpandibles/efectos adversos , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Oncogenic RAS mutations are negative biomarkers of response to epidermal growth factor receptor (EGFR) blockade. RAS mutations are usually detected in biopsies of primary colorectal tumors. However, the genomic profiles of primary tumors and metastases are not always concordant, and chemotherapeutic agents can alter the tumor molecular landscape. Cell-free DNA (cfDNA) is a novel tool to detect molecular heterogeneity. This study evaluated the clinical utility of cfDNA to predict primary or secondary resistance to EGFR blockade in patients with metastatic colorectal cancer. Thirty metastatic colorectal cancer patients without RAS and BRAF mutations were prospectively enrolled and treated with cytotoxic agents and EGFR blockade as first-line therapy. cfDNA was analyzed for the presence of RAS, BRAF, and EGFR (S492R) point mutations before initiating chemotherapy and every 2 months during chemotherapy. The analysis was performed in 223 plasma samples from all 30 patients. Of the 30 patients, five had RAS mutations in their cfDNA before starting chemotherapy and did not respond. Twenty-four of the remaining 25 patients without cfDNA RAS mutations had a response. Twenty of the 24 responders developed secondary resistance and cfDNA RAS mutations were found in 17 of the 20. cfDNA BRAF mutations were found in seven, and EGFR mutations were found in eight of the 20 patients. Emerging RAS, BRAF, and EGFR mutations occurred in patients with primary and secondary resistance to EGFR blockade. The detection of these mutations in cfDNA is a promising approach to predict treatment response and secondary resistance.
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Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ácidos Nucleicos Libres de Células/genética , Cetuximab/administración & dosificación , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación , Compuestos Organoplatinos/uso terapéutico , Panitumumab/administración & dosificación , Proyectos Piloto , Resultado del TratamientoRESUMEN
A woman in her 60s underwent lower endoscopy due to a positive fecal occult blood test. A type 2 tumor was found in the cecum, and a biopsy resulted in the diagnosis of adenocarcinoma(tub2). Contrast-enhanced CT showed an enlarged paracolonic lymph node but no distant metastasis, so the patient underwent a laparoscopic-assisted ileocolic resection and D3 lymph node dissection for cecum cancer. The pathology was pT3, pN2b, pM0, pStage â ¢c, and 12 courses of FOLFOX were administered as adjuvant chemotherapy. Twenty-four months after the completion of adjuvant chemotherapy, an elevated CEA was observed, and a PET-CT was performed, which showed multiple peritoneal disseminated nodules with FDG accumulation. Based on this finding, CAPOX/bevacizumab therapy was introduced, and on completion of 4 courses, the PET-CT showed a decrease in the size of the nodules and the disappearance of FDG accumulation. Based on this, the patient underwent resection. A peritoneal dissemination resection and bilateral ovariectomy were laparoscopically performed, and the patient is currently under observation. In patients with metastatic recurrence of peritoneal dissemination who underwent complete resection, treatment with CAPOX/bevacizumab may allow for disease control and provide a long-term prognosis.
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Neoplasias del Colon , Neoplasias Colorrectales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias del Colon/cirugía , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
We recruited 56 colorectal cancer patients and compared the mutational spectrum of tumor tissue DNA, circulating cell-free DNA (ccfDNA) and circulating tumor cell (CTC) DNA (ctcDNA) to evaluate the potential of liquid biopsy to detect heterogeneity of cancer. Tumor tissue DNA, ccfDNA, and ctcDNA were extracted from each patient and analyzed using next-generation sequencing (NGS) and digital PCR. To maximize yields of CTC, three antibodies were used in the capture process. From 34 untreated patients, 53 mutations were detected in tumor tissue DNA using NGS. Forty-seven mutations were detected in ccfDNA, including 20 not detected in tissues. Sixteen mutations were detected in ctcDNA, including five not detected in tissues. In 12 patients (35.3%), mutations not found in tumor tissues were detected by liquid biopsy: nine (26.5%) in ccfDNA only and three (8.8%) in ctcDNA only. Combination analysis of the two liquid biopsy samples increased the sensitivity to detect heterogeneity. From 22 stage IV patients with RAS mutations in their primary tumors, RAS mutations were detected in 14 (63.6%) ccfDNA and in eight (36.4%) ctcDNA using digital PCR. Mutations not detected in primary tumors can be identified in ccfDNA and in ctcDNA, indicating the potential of liquid biopsy in complementing gene analysis. Combination analysis improves sensitivity. Sensitivity to detect cancer-specific mutations is higher in ccfDNA compared with ctcDNA.
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Ácidos Nucleicos Libres de Células/análisis , Neoplasias Colorrectales/genética , ADN de Neoplasias/análisis , Mutación , Células Neoplásicas Circulantes/química , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Biopsia Líquida , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
The incidence of rare neuroendocrine tumors (NET) is rapidly increasing. Neuroendocrine carcinoma (NEC) is a NET with poorly differentiated histological features, high proliferative properties and associated poor prognoses. As these carcinomas are so rare and, thus, affect only a small number of patients allowing for few cell lines to be derived from patient biopsies, the histological, immunohistochemical, and clinical characteristics associated with colorectal NEC and NEC in other organs have yet to be clearly defined. Herein, we describe the establishment of a novel NEC cell line (SS-2) derived from a tumor resection of the ascending colon from a 59-year-old Japanese woman. The histological, electron microscopic and immunohistochemical features of chromogranin A (CgA) as well as confirmation of synaptophysin positivity in this tumor were typical of those commonly observed in surgically resected colorectal NEC. Further, the Ki-67 labeling index of the resected tumor was >20% and, thus, the tumor was diagnosed as an NEC of the ascending colon. The SS-2 cell line maintained characteristic features to those of the resected tumor, which were further retained following implantation into subcutaneous tissues of nude mice. Additionally, when SS-2 cells were seeded into ultra-low attachment plates, they formed spheres that expressed higher levels of the cancer stem cell (CSC) marker CD133 compared to SS-2 cells cultured under adherent conditions. SS-2 cells may, therefore, contribute to the current knowledge on midgut NEC biological function while providing a novel platform for examining the effects of colorectal NEC drugs, including CSC.
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Carcinoma Neuroendocrino/patología , Colon Ascendente/patología , Neoplasias del Colon/patología , Antígeno AC133/análisis , Animales , Carcinoma Neuroendocrino/tratamiento farmacológico , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Trasplante de NeoplasiasRESUMEN
BACKGROUND: Liquid biopsy is a collective term that refers to the analysis of tumor-derived biomarkers isolated from biological fluids of cancer patients. Recently, many authors reported the usefulness of liquid biopsy for the management of malignancy. Summary and Key Messages: The peripheral blood of cancer patients is a pool of cells and/or cell products derived from the primary or metastatic tumor, including circulating tumor cells (CTCs), circulating free (cf) DNA or RNA, and exosomes containing proteins, nucleic acids, and lipids. CTCs are tumor cells that can be isolated from peripheral blood. Free circulating DNA with a tumor-specific mutation is called circulating tumor DNA (ctDNA). Some patients who undergo curative surgery experience recurrent disease, which can be due to the presence of minimal residual disease (MRD). Thus, MRD indicates a high risk of relapse. Detection of ctDNA or CTC after surgery is a direct proof of MRD. Molecular volume (e.g., the number of CTCs and level of ctDNA) might reflect tumor burden, thus high molecular volume may indicate poor prognosis. The most notable application of liquid biopsy in cancer is to understand spatial and temporal heterogeneities. Heterogeneity is one of the causes of refractoriness and hampers prediction of chemotherapeutic effect. Emerging mutations that are not present in primary tumors but are found in their metastases can be detected in ctDNA. Some colorectal cancer patients with wild-type RAS do not respond to epidermal growth factor receptor blockade. In a subset of these patients, RAS mutation is detected in ctDNA, indicating heterogeneity.
Asunto(s)
Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Biopsia Líquida/métodos , Neoplasia Residual/diagnóstico , Células Neoplásicas Circulantes/metabolismo , Biomarcadores de Tumor/sangre , Colectomía , Neoplasias Colorrectales/cirugía , ADN de Neoplasias/sangre , HumanosRESUMEN
Chemoradiotherapy(CRT)for locally recurrent rectal cancer can shrink the tumor and permit R0 resection; however, its effectiveness and safety have not been established. Herein, we report a case of a 60s man with locally recurrent rectal cancer invading the surrounding organs who was administered CRT followed by R0 laparoscopic-assisted abdominoperineal resection( APR). Local recurrence was detected 11 months after laparoscopic-assisted low anterior resection(pT3N0M0, pStage â ¡). After tumor shrinkage by CRT(capecitabine 3,000mg/day plus 45 Gy/25 Fr), laparoscopic-assisted APR was performed. The pathological findings showed a pathological complete response(pCR). The patient had not experienced recurrent disease at 6 months after the second surgery. CRT may improve the prognosis of patients with locally recurrent rectal cancer, especially those with possibly unresectable tumors.
Asunto(s)
Neoplasias del Recto , Quimioradioterapia , Humanos , Masculino , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/terapia , Resultado del TratamientoRESUMEN
Ovarian metastasis of colorectal cancer is associated with poor prognosis. Recent advances in chemotherapy may improve this prognosis. In this retrospective study, we evaluated indicators of poor prognosis for ovarian metastasis of colorectal cancer. Twenty patients, who were diagnosed with ovarian metastasis of colorectal cancer from April 2000 to December 2017, were enrolled. Oophorectomy was performed in 18 of the 20 patients. Postoperative chemotherapy was provided to 13 patients, and molecular targeting agents were administered in 5 patients. Metastases to other organs besides the ovaries, premenopausal condition, undifferentiated histologic type of the primary tumor, and no resection of ovarian metastases were identified as indicators of poor prognosis. The 3-year survival rate was 15%, and the 5-year survival rate was 0%. In conclusion, oophorectomy can improve the prognosis of patients with ovarian metastasis of colorectal cancer. However, prognostic improvement due to molecular target agents was not shown.