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BACKGROUND/AIM: Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme in tryptophan metabolism and plays an important role in immunosuppression. The effects of IDO1 on tumor invasion and metastasis have been studied in several types of malignancies. However, the role of IDO1 in these steps in colorectal cancer (CRC) has not been elucidated. Therefore, we aimed to investigate the effects of IDO1 on invasion, migration, and epithelial-mesenchymal transition (EMT) in CRC cells. MATERIALS AND METHODS: All experiments were performed using the DLD-1 colon cancer cell line that expresses IDO1. We conducted a scratch wound healing assay and Boyden chamber assay to investigate the impact of IDO1 on DLD-1 cell migration and invasion, respectively, in the presence and absence of the IDO1 inhibitor L-1-methyl-tryptophan (L-1-MT). Additionally, western blotting was performed to analyze alterations in the expression of EMT-related markers caused by L-1-MT. RESULTS: High expression of IDO1 was confirmed in the cytoplasm of DLD-1 by immunofluorescence staining. In the scratch wound healing assay, the invasion ability of DLD-1 cells decreased to 62% after treatment with L-1-MT at 1,000 µM for 24 h. In the Boyden chamber assay, the migration of DLD-1 cells was suppressed by 85% after treatment with L-1-MT at 2,500 µM for 24 h. L-1-MT treatment increased the expression level of E-cadherin and decreased the expression levels of vimentin, Snail, and Slug. CONCLUSION: IDO1 inhibition reduced the invasion and migration ability of IDO1-expressing DLD-1 colon cancer cells, which was accompanied by altered expression of EMT-related proteins. IDO1 could be a potential target for the treatment of advanced CRC.
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Movimiento Celular , Neoplasias del Colon , Transición Epitelial-Mesenquimal , Indolamina-Pirrol 2,3,-Dioxigenasa , Invasividad Neoplásica , Triptófano , Humanos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Movimiento Celular/efectos de los fármacos , Neoplasias del Colon/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Línea Celular Tumoral , Triptófano/análogos & derivados , Triptófano/farmacología , Triptófano/metabolismo , Inhibidores Enzimáticos/farmacologíaRESUMEN
BACKGROUND/AIM: The usefulness of robotic surgery compared to laparoscopic surgery for rectal cancer has been reported; however, few reports exist on robotic abdominoperineal resection (APR). The aim of this study was to compare the outcomes of robotic and laparoscopic surgery to determine their usefulness in patients with locally advanced rectal cancer who had undergone preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: This retrospective study included 43 patients with locally advanced rectal cancer who underwent preoperative CRT and robotic (22 patients) or laparoscopic APR (21 patients) between December 2012 and September 2022. We examined the short- and long-term outcomes in the robotic and laparoscopic groups. RESULTS: The median follow-up durations were 36 and 48 months for the robotic and laparoscopic groups, respectively. No significant differences in operative time, intraoperative blood loss, or overall complication rates were observed. However, the incidence of organ/space surgical site infection (SSI) was significantly lower in the robotic surgery group than in the laparoscopic group (9.1% vs. 38.1%, p=0.034) and the 3-year overall survival rate was significantly higher in the robotic surgery group than in the laparoscopic group (95% vs. 67%, p=0.029). CONCLUSION: Robotic APR was associated with a significantly lower rate of organ/space SSIs than the laparoscopic approach, indicating the usefulness of the robotic approach.
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Quimioradioterapia , Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Neoplasias del Recto/mortalidad , Masculino , Laparoscopía/métodos , Femenino , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Persona de Mediana Edad , Anciano , Quimioradioterapia/métodos , Resultado del Tratamiento , Estadificación de Neoplasias , Estudios Retrospectivos , Adulto , Proctectomía/métodosRESUMEN
INTRODUCTION: Adjuvant chemotherapy (AC) after radical surgery following preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) is now the standard of care. The identification of risk factors for the discontinuation of AC is important for further improvements in survival. We herein examined the prognostic impact of chemotherapy compliance and its relationship with the prognostic nutritional index (PNI) before surgery. METHODS: A total of 335 stage II-III LARC patients who underwent preoperative CRT between 2003 and 2022 at the University of Tokyo Hospital were retrospectively reviewed. We excluded patients with recurrence during AC and those who had not received AC. The relationship between AC and long-term outcomes and that between PNI values and the duration of AC were examined. RESULTS: Thirty-one patients discontinued AC and 62 continued AC. Recurrence-free survival (RFS) was significantly shorter in patients who discontinued AC (p = 0.0056). The discontinuation of AC was identified as an independent risk factor for RFS (hazard ratio [HR]: 2.24, p = 0.0233). Twenty-one patients were classified as having low PNI (less than 40), which correlated with an older age, low body mass index, and incomplete AC. Low PNI was an independent risk factor for a shorter duration of AC (HR: 2.53, p = 0.0123). CONCLUSION: The discontinuation of AC was related to poor RFS in patients with LARC undergoing preoperative CRT. Furthermore, a low PNI value was identified as a risk factor for a shorter duration of AC.
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PURPOSE: This study aimed to clarify the relationship between changes in elasticity and anorectal function before and after chemoradiotherapy. METHODS: This is a single-center prospective cohort study (Department of Surgical Oncology, The University of Tokyo). We established a technique to quantify internal anal sphincter hardness as elasticity using transanal ultrasonography with real-time tissue elastography. Twenty-seven patients with post-chemoradiotherapy rectal cancer during 2019-2022 were included. Real-time tissue elastography with transanal ultrasonography was performed before and after chemoradiotherapy to measure internal anal sphincter hardness as "elasticity" (hardest (0) to softest (255); decreased elasticity indicated sclerotic changes). The relationship between the increase or decrease in elasticity pre- and post-chemoradiotherapy and the maximum resting pressure, maximum squeeze pressure, and Wexner score were the outcome measures. RESULTS: A decrease in elasticity was observed in 16/27 (59.3%) patients after chemoradiotherapy. Patients with and without elasticity decrease after chemoradiotherapy comprised the internal anal sphincter sclerosis and non-sclerosis groups, respectively. The maximum resting pressure post-chemoradiotherapy was significantly high in the internal anal sphincter sclerosis group (63.0 mmHg vs. 47.0 mmHg), and a majority had a worsening Wexner score (60.0% vs. 18.2%) compared with that of the non-sclerosis group. Decreasing elasticity (internal anal sphincter sclerosis) correlated with a higher maximum resting pressure (r = 0.36); no correlation was observed between the degree of elasticity change and maximum squeeze pressure. CONCLUSION: Internal anal sphincter sclerosis due to chemoradiotherapy may correlate to anorectal dysfunction.
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Canal Anal , Quimioradioterapia , Diagnóstico por Imagen de Elasticidad , Neoplasias del Recto , Humanos , Canal Anal/diagnóstico por imagen , Canal Anal/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Quimioradioterapia/efectos adversos , Anciano , Neoplasias del Recto/terapia , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/fisiopatología , Recto/fisiopatología , Recto/diagnóstico por imagen , Elasticidad , Estudios Prospectivos , Adulto , Cuidados Preoperatorios , PresiónRESUMEN
BACKGROUND: Minimally invasive surgery (MIS), such as laparoscopic and robotic surgery for rectal cancer, is performed worldwide. However, limited information is available on the advantages of MIS over open surgery for multivisceral resection for cases clinically invading adjacent organs. PATIENTS AND METHODS: This was a retrospective propensity score-matching study of consecutive clinical T4b rectal cancer patients who underwent curative intent surgery between 2006 and 2021 at the University of Tokyo Hospital. RESULTS: Sixty-nine patients who underwent multivisceral resection were analyzed. Thirty-three patients underwent MIS (the MIS group), while 36 underwent open surgery (the open group). Twenty-three patients were matched to each group. Conversion was required in 2 patients who underwent MIS (8.7%). R0 resection was achieved in 87.0% and 91.3% of patients in the MIS and open groups, respectively. The MIS group had significantly less blood loss (170 vs. 1130 mL; p < 0.0001), fewer Clavien-Dindo grade ≥ 2 postoperative complications (30.4% vs. 65.2%; p = 0.0170), and a shorter postoperative hospital stay (20 vs. 26 days; p = 0.0269) than the open group. The 3-year cancer-specific survival rate, relapse-free survival rate, and cumulative incidence of local recurrence were 75.7, 35.9, and 13.9%, respectively, in the MIS group and 84.5, 45.4, and 27.1%, respectively, in the open group, which were not significantly different (p = 0.8462, 0.4344, and 0.2976, respectively). CONCLUSION: MIS had several short-term advantages over open surgery, such as lower complication rates, faster recovery, and a shorter hospital stay, in rectal cancer patients who underwent multivisceral resection.
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Laparoscopía , Tiempo de Internación , Invasividad Neoplásica , Complicaciones Posoperatorias , Puntaje de Propensión , Neoplasias del Recto , Humanos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Laparoscopía/métodos , Tiempo de Internación/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Robotizados/métodos , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Resultado del Tratamiento , Vísceras/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodosRESUMEN
BACKGROUND: Laparoscopic colon surgery frequently requires performing maneuvers under mirror-images conditions; the complexity differs depending on the surgical site location in the abdominal cavity. However, no previous reports have examined this. METHODS: Eleven surgeons participated in this study. Operations were performed on 25 points placed at the bottom and sides of a laparoscopic training box under mirror-image conditions. The mean time-point required to operate at each point and variation between surgeons were evaluated. RESULTS: When the right hand was used, time-points to touch the right side-superficial ends were 0.50 to 0.58 and 0.27 to 0.45 for the other sites. With the left hand, time-points to touch the left side-superficial ends were 0.58 to 0.63 and 0.28 to 0.51 for the other sites, indicating that the most difficult manipulation was at the proximal site of the surgical port. The variation in the difficulty according to the spots increased with a decrease in the surgeon's experience (right hand, r =-0.248; left hand, r =-0.491). CONCLUSIONS: In performing laparoscopic surgery under mirror-image conditions, the technical difficulty varies by location, and operating in locations close to the forceps port is the most difficult.
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Competencia Clínica , Laparoscopía , Humanos , Laparoscopía/métodos , Tempo Operativo , MasculinoRESUMEN
BACKGROUND: The standard treatment for anal squamous cell carcinoma is chemoradiation therapy (CRT), but there is a possibility of over-treatment for early-stage disease. cTisN0 and cT1N0 disease is currently indicated for local excision, but it is unclear whether the indication of local excision can be expanded to cT2N0 disease. METHODS: 126 patients with cTis-T2N0 anal cancer treated at 47 centers in Japan between 1991 and 2015 were included. Patients were first classified into the CRT group and surgical therapy group according to the initial therapy, and the latter was further divided into local excision (LE) and radical surgery (RS) groups. We compared prognoses among the groups, and analyzed risk factors for recurrence after local excision. RESULTS: The CRT group (n = 87) and surgical therapy group (n = 39) showed no difference in relapse-free survival (p = 0.29) and overall survival (p = 0.94). Relapse-free survival curves in the LE (n = 23) and RS groups (n = 16) overlapped for the initial 3 years, but the curve for the LE group went lower beyond (p = 0.33). By contrast, there was no difference in overall survival between the two groups (p = 0.98). In the LE group, the majority of recurrences distributed in locoregional areas, which could be managed by salvage treatments. Muscular invasion was associated with recurrence after local excision (hazard ratio: 22.91, p = 0.011). CONCLUSION: LE may be applied to selected patients with anal cancer of cTis-T2N0 stage. Given the high risk of recurrence in cases with muscular invasion, it may be important to consider close surveillance and additional treatment in such patients.
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Neoplasias del Ano , Carcinoma de Células Escamosas , Recurrencia Local de Neoplasia , Humanos , Neoplasias del Ano/patología , Neoplasias del Ano/cirugía , Neoplasias del Ano/terapia , Masculino , Femenino , Anciano , Persona de Mediana Edad , Japón , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Estadificación de Neoplasias , Adulto , Quimioradioterapia , Anciano de 80 o más Años , Pronóstico , Supervivencia sin Enfermedad , Estudios RetrospectivosRESUMEN
In Western countries, the gold-standard therapeutic strategy for rectal cancer is preoperative chemoradiotherapy (CRT) following total mesorectal excision (TME), without lateral lymph node dissection (LLND). However, preoperative CRT has recently been reported to be insufficient to control lateral lymph node recurrence in cases of enlarged lateral lymph nodes before CRT, and LLND is considered necessary in such cases. We performed a literature review on aspects of pelvic anatomy associated with rectal surgery and LLND, and then combined this information with our experience and knowledge of pelvic anatomy. In this review, drawing upon research using a 3-dimensional anatomical model and actual operative views, we aimed to clarify the essential anatomy for LLND. The LLND procedure was developed in Asian countries and can now be safely performed in terms of functional preservation. Nonetheless, the longer operative time, hemorrhage, and higher complication rates with TME accompanied by LLND than with TME alone indicate that LLND is still a challenging procedure. Laparoscopic or robotic LLND has been shown to be useful and is widely performed; however, without a sufficient understanding of anatomical landmarks, misrecognition of vessels and nerves often occurs. To perform safe and accurate LLND, understanding the landmarks of LLND is essential.
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BACKGROUND: Carcinoembryonic antigen (CEA) monitoring facilitates the detection of recurrence in patients with colorectal cancer (CRC) after resection. False-positive CEA has been reported in CRC patients with certain comorbidities or smokers. However, limited information is currently available on the frequency of and changes in falsely elevated CEA levels in patients without these conditions. MATERIALS AND METHODS: We retrospectively examined CRC patients who underwent surgical resection at our hospital between 2001 and 2017, had no recurrence for at least five years, and were free of known factors that may increase CEA. Postoperative CEA levels were retrieved until 2 years before the last contact. For comparison, we similarly selected patients who developed recurrence after resection of CRC during the same period, and CEA levels at initial presentation, at nadir, and at the time of recurrence were reviewed. The patterns of elevated CEA (>5 ng/ml) were classified as transient, repeated, or persistent based on longitudinal changes. The relationships between CEA and carbohydrate antigen 19-9, transaminases, creatinine, and C-reactive protein were examined. RESULTS: CEA elevation occurred in 90 (20%) out of 446 eligible patients without recurrence at least once during the mean postoperative period of 50.5 months, whereas CEA was >5 ng/ml in 117 (53%) of 221 patients when they developed recurrence. Twenty-seven patients without recurrence showed a transient elevation in CEA, 45 repeated elevations, and 18 a persistent elevation; the frequency of a high preoperative CEA level increased in this order. The majority (98%) of false elevations ranged between 5 and 15 ng/ml. CEA was not associated with other laboratory data. CONCLUSIONS: Unexplained CEA elevations were observed in 20% of recurrence-free CRC patients after surgery, and were classified into three patterns based on longitudinal changes. A more detailed understanding of patient-specific fluctuations in CEA will prevent unnecessary imaging studies and reduce medical costs.
Limited information is currently available on the frequency of and changes in falsely elevated carcinoembryonic antigen (CEA) levels after surgery for colorectal cancer. Unexplained postoperative CEA elevations were detected in 20% of colorectal cancer patients. The patterns of these elevations were classified into transient, repeated, and persistent.
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Antígeno Carcinoembrionario , Neoplasias Colorrectales , Humanos , Estudios de Seguimiento , Estudios Retrospectivos , Incidencia , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Colorrectales/cirugía , Periodo PosoperatorioRESUMEN
BACKGROUND: A laparoscopic approach generally provides several benefits in patients who undergo colon or rectal surgery without jeopardizing oncological outcomes. However, there is a paucity of studies on comparative outcomes of laparoscopic versus open approaches for second primary colorectal lesions after colectomy or proctectomy. METHODS: From patients with colorectal disease who underwent surgery between 2008 and 2022 at our hospital, we collected 69 consecutive patients who had previous colorectal surgery for this retrospective study. Based on the second surgery approach (laparoscopic or open), patients were classified into the Lap (n = 37) or Op group (n = 32). Patients' baseline data and perioperative and postoperative outcomes were compared between the two groups. RESULTS: Four patients (11%) of the Lap group needed conversion to laparotomy. The intraoperative blood loss was lower in the Lap group than the Op group (median: 45 ml vs. 205 ml, p = 0.001). The time to first bowel movement was shorter in the Lap group than the Op group (median: 2.8 days vs. 3.6 days, p = 0.007). The operative time, frequencies of postoperative morbidities, and overall survival did not differ between the two groups. CONCLUSION: Laparoscopic surgery appeared feasible and beneficial for selected patients undergoing second colorectal resection after colectomy or proctectomy regarding blood loss and bowel function recovery without affecting other outcomes.
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Neoplasias Colorrectales , Laparoscopía , Proctectomía , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Colectomía , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patologíaRESUMEN
BACKGROUND: The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis. Moreover, the median survival time was 29.3 months, which was longer than that observed in previous studies. Here, we planned the phase II trial of ip PTX: the iPac-02 trial. METHODS: This multicenter, open-label, single assignment interventional clinical study includes patients with colorectal cancer with unresectable peritoneal carcinomatosis. FOLFOX-bevacizumab or CAPOX-bevacizumab is administered concomitantly as systemic chemotherapy. PTX 20 mg/m2 is administered weekly through the peritoneal access port in addition to these conventional systemic chemotherapies. The response rate is the primary endpoint. Progression-free survival, overall survival, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, safety, and response rate to peritoneal metastases are the secondary endpoints. A total of 38 patients are included in the study. In the interim analysis, the study will continue to the second stage if at least 4 of the first 14 patients respond to the study treatment. The study has been registered at the Japan Registry of Clinical Trials (jRCT2031220110). RESULTS: We previously conducted phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis [1]. In the study, three patients underwent mFOLFOX, bevacizumab, and weekly ip PTX, and the other three patients underwent CAPOX, bevacizumab, and weekly ip PTX treatment. The dose of PTX was 20 mg/m [2]. The primary endpoint was the safety of the chemotherapy, and secondary endpoints were response rate, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, progression-free survival, and overall survival. Dose limiting toxicity was not observed, and the adverse events of ip PTX combined with oxaliplatin-based systemic chemotherapy were similar to those described in previous studies using systemic chemotherapy alone [3, 4]. The response rate was 25%, peritoneal cancer index improvement rate was 50%, and cytology in peritoneal lavage turned negative in all the cases. The progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months [5], which was longer than that observed in previous studies. CONCLUSION: Here, we planned the phase II trial of ip paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: the iPac-02 trial.
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Neoplasias Colorrectales , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Bevacizumab/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Colorrectales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
BACKGROUND: Total neoadjuvant therapy (TNT) is a novel treatment strategy that is an alternative to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, an optimal protocol for TNT has not yet been established. The present study will be an open-label, single-arm, single-center trial to develop a new protocol. METHODS: Thirty LARC patients at high risk of distant metastasis will receive CRT consisting of long-course radiation, concurrent with tegafur/uracil, oral leucovorin, irinotecan (TEGAFIRI), followed by mFOLFOX-6 or CAPOX before undergoing surgery. DISCUSSION: Since previous findings showed a high percentage of grade 3-4 adverse events with the TEGAFIRI regimen for CRT and TNT, the primary outcome of this study will be safety and feasibility. Our regimen for CRT consists of the biweekly administration of irinotecan for good patient compliance. The novel combination approach of this treatment may improve the long-term outcomes of LARC. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs031210660.
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Neoplasias del Recto , Tegafur , Humanos , Irinotecán/uso terapéutico , Oxaliplatino , Leucovorina , Terapia Neoadyuvante/métodos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia/métodos , Fluorouracilo/uso terapéutico , Estadificación de Neoplasias , Ensayos Clínicos Fase II como AsuntoRESUMEN
AIM: The preoperative prediction of lymph node metastasis of well-differentiated rectal neuroendocrine tumours is highly desirable and useful in defining surgical indication more accurately. We aimed to evaluate lymph node metastasis in rectal neuroendocrine neoplasms using multiple imaging modalities. METHODS: The clinical records and radiological images of 70 patients with well-differentiated rectal neuroendocrine tumours who received treatment at the University of Tokyo Hospital between 2010 and 2022 were retrospectively analysed. The relationship between evaluation by multiple imaging modalities and pathological lymph node metastasis was analysed. RESULTS: The receiver operating characteristic curves showed that a maximum lymph node diameter ≥4 mm on computed tomography and ≥8 mm on magnetic resonance imaging were the optimal predictive factors for lymph node metastasis. Accumulation in the lymph nodes on somatostatin receptor scintigraphy (P = 0.058) and Delle's findings on colonoscopy (P = 0.014) were also significant predictors of pathological lymph node positivity, and combination of multiple modalities was useful. Pathologically, lymphatic (P = 0.0030)/venous (P = 0.0007) invasion were risk factors for lymph node metastasis. CONCLUSIONS: In addition to pathological risk factors, a combination of multiple radiological imaging modalities is useful for predicting lymph node metastasis in well-differentiated rectal neuroendocrine tumours.
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Tumores Neuroendocrinos , Neoplasias del Recto , Humanos , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Tumores Neuroendocrinos/cirugía , Estudios Retrospectivos , Ganglios Linfáticos/patología , Imagen por Resonancia Magnética , Neoplasias del Recto/cirugíaRESUMEN
The genetic risk factors for anastomotic recurrence (AR) after curative surgery for colorectal cancer (CRC) are unclear. The present study is a single-center retrospective observational study that aimed to elucidate the association between the KRAS G13D mutation and AR in CRC. The present study included 21 patients with AR and 67 patients with non-anastomotic local recurrence (NALR) following curative surgery for CRC between January 2005 and December 2019. KRAS G13D mutation status was examined by droplet digital polymerase chain reaction. Data of clinicopathological findings and oncological outcomes were analyzed and compared between the AR group and the matched NALR group. The prevalence of the KRAS G13D mutation was significantly higher in the AR group (AR vs. NALR, 33.3 vs. 4.8%; P=0.047). Comparing the KRAS G13D mutation-positive and KRAS G13D mutation-negative patients in the AR group, there was no significant difference in the time from initial surgery to AR or resection rate of AR; however, all patients with KRAS G13D mutation who underwent resection of AR had subsequent recurrence within 2 years after resection, and overall survival was poor (3-year survival rate: Positive vs. negative, 68.6 vs. 90.9%; P=0.02). The prevalence of the KRAS G13D mutation was significantly higher in patients with AR, and KRAS G13D-mutant patients with AR had a poorer prognosis than those that were negative for the KRAS G13D mutation. In conclusion, postoperative surveillance and treatment strategies should be considered with attention to the possibility of AR and subsequent recurrence in KRAS G13D-mutant patients.
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Adenocarcinoma is a common histological type of ulcerative colitis-associated cancer (UCAC), whereas neuroendocrine carcinoma (NEC) is extremely rare. UCAC is generally diagnosed at an advanced stage, even with regular surveillance colonoscopy. A 41-year-old man with a 17-year history of UC began receiving surveillance colonoscopy at the age of 37 years; 2 years later, dysplasia was detected in the sigmoid colon, and he underwent colonoscopy every 3 to 6 months. Approximately 1.5 years thereafter, a flat adenocarcinoma lesion occurred in the rectum. Flat lesions with high-grade dysplasia were found in the sigmoid colon and surrounding area. The patient underwent laparoscopic total proctocolectomy and ileal pouch-anal anastomosis with ileostomy. Adenocarcinoma was diagnosed in the sigmoid colon and NEC in the rectum. One year postoperation, recurrence or metastasis was not evident. Regular surveillance colonoscopy is important in patients with long-term UC. A histological examination of UCAC might demonstrate NEC.
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A 71-year-old man was diagnosed with advanced non-small cell lung carcinoma and treated with chemotherapy developed ileocecal diverticulitis three times over the last 2 months of receiving second-line treatment. During the fourth diverticulitis event, the patient presented with fever and abdominal pain, worsening after 5 days. Abdominal computed tomography showed ascites and intra-abdominal free air, suggesting bowel perforation with acute diffuse peritonitis. We performed emergency surgery; the surgical findings showed diverticulosis with perforated diverticula in the ileocecal region. We performed ileocecal resection, an ileostomy and a mucous fistula of the ascending colon. Histopathological examinations revealed pseudodiverticula at the perforation, where the mucosa was depressed through the muscularis propria. Hence, we diagnosed perforated ileal diverticulitis. Repeated diverticulitis triggered by chemotherapy might have resulted in perforation. Small bowel diverticula are rare, but diverticulitis can occur in patients receiving chemotherapy and with cases of unexplained fever and abdominal pain.
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Colonic metastasis from ovarian cancer is extremely rare, with only seven reported cases. A 77-year-old woman who had previously undergone surgery for ovarian cancer was admitted to a local hospital with anal bleeding. Histopathological analysis confirmed the presence of adenocarcinoma. Colonoscopy revealed a descending colon tumor. The patient was diagnosed with Union for International Cancer Control T3N0M0 descending colon cancer or colon metastasis of the ovarian cancer. Laparoscopic left colectomy was performed; intraoperative frozen section diagnosis confirmed metastasis from ovarian cancer, and the absence of invasion to the serosal surface suggested hematogenous metastasis. This is the first case of colonic metastasis from ovarian cancer that was diagnosed using an intraoperative frozen section and laparoscopically treated.
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Total mesorectal excision (TME) for rectal cancer is often technically challenging. We aimed to develop a method for three-dimensional (3D) visualization of the TME dissection plane and to evaluate its ability to predict surgical difficulty. Sixty-six patients with lower rectal cancer who underwent robot-assisted surgery were retrospectively analyzed. A 3D TME dissection plane image for each case was reconstructed using Ziostation2. Subsequently, a novel index that reflects accessibility to the deep pelvis during TME, namely, the TME difficulty index, was defined and measured. Representative bony pelvimetry parameters and clinicopathological factors were also analyzed. The operative time for TME was used as an indicator of surgical difficulty. Univariate regression analysis revealed that sex, body mass index, mesorectal fat area, and TME difficulty index were associated with the operative time for TME, whereas bony pelvimetry parameters were not. Multivariate regression analysis found that TME difficulty index (ß = - 0.398, P = 0.0025) and mesorectal fat area (ß = 0.223, P = 0.045) had significant predictability for the operative time for TME. Compared with conventional bony pelvimetry parameters, the TME difficulty index and mesorectal fat area might be more useful in predicting the difficulty of rectal cancer surgery.
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Laparoscopía , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Imagenología Tridimensional , Recto/diagnóstico por imagen , Recto/cirugía , Recto/patología , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Pelvis/patología , Laparoscopía/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Anastomotic recurrence is thought to be caused by implantation of tumor cells to the anastomotic line; however, its risk factors and prognostic significance remain unclear. OBJECTIVE: This study aimed to clarify the risk factors for anastomotic recurrence in colorectal cancer and assess the prognosis in comparison to nonanastomotic local recurrence. DESIGN: A single-center retrospective observational study. SETTINGS: The medical records of the study participants were retrospectively collected from the Department of Surgical Oncology at the University of Tokyo Hospital database. PATIENTS: This study included 1584 patients with colorectal cancer who underwent surgical resection between January 2005 and December 2017. We focused on 15 patients who had an anastomotic recurrence. MAIN OUTCOME MEASURES: The main outcome measures were the risk factors of anastomotic recurrence at the primary resection and prognosis data in comparison to that of nonanastomotic local recurrence. RESULTS: There were 15 patients (0.95%) with anastomotic recurrence and 35 (2.21%) with nonanastomotic local recurrence. Univariate analysis revealed that lymph node metastasis and advanced T stage are the risk factors for anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that of those with nonanastomotic local recurrence who underwent resection. LIMITATIONS: The small number of patients with anastomotic recurrence is a major limitation of this study. Additionally, the retrospective study design may have increased the risk of selection bias. CONCLUSIONS: Lymph node metastasis and advanced T stage were associated with anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that with resected nonanastomotic local recurrence. Thus, surveillance should be carefully continued while considering the poor prognosis of patients with anastomotic recurrence. See Video Abstract at http://links.lww.com/DCR/C92 . CARACTERSTICAS CLINICOPATOLGICAS DE LA RECURRENCIA ANASTOMTICA DESPUS DE LA RESECCIN CURATIVA DEL CNCER COLORRECTAL COMPARACIN CON LAS RECURRENCIAS LOCALES NO ANASTOMTICAS: ANTECEDENTES:Se cree que la recurrencia anastomótica es causada por la implantación de células tumorales en la línea anastomótica; sin embargo, los factores de riesgo asociados y el significado en cuanto a pronóstico siguen sin estar claros.OBJETIVO:Este estudio tuvo como objetivo aclarar los factores de riesgo para la recurrencia anastomótica en el cáncer colorrectal y evaluar el pronóstico en comparación con la recurrencia local no anastomótica.DISEÑO:Un estudio observacional retrospectivo de un solo centro.ESCENARIO:Los registros médicos de los participantes del estudio se recopilaron retrospectivamente de la base de datos del Departamento de Cirugía Oncológica del Hospital de la Universidad de Tokio.PACIENTES:Este estudio incluyó a 1584 pacientes con cáncer colorrectal que se sometieron a resección quirúrgica entre enero de 2005 y diciembre de 2017. Nos enfocamos en 15 pacientes que tuvieron recurrencia anastomótica.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron los factores de riesgo de recurrencia anastomótica en la resección primaria y los datos de pronóstico en comparación con la recurrencia local no anastomótica.RESULTADOS:Hubo 15 pacientes (0.95%) con recurrencia anastomótica y 35 (2.21%) con recurrencia local no anastomótica. El análisis univariable reveló que la metástasis en los ganglios linfáticos y el estadio T avanzado son los factores de riesgo para la recurrencia anastomótica. El pronóstico de los pacientes con recidiva anastomótica fue similar al de aquellos con recidiva local no anastomótica sometidos a resección.LIMITACIONES:El pequeño número de pacientes con recurrencia anastomótica es una limitación importante de este estudio. Además, el diseño retrospectivo del estudio puede haber aumentado el riesgo de sesgo de selección.CONCLUSIONES:La metástasis en los ganglios linfáticos y el estadio T avanzado se asociaron con recurrencia anastomótica. El pronóstico de los pacientes con recidiva anastomótica fue similar al de la recidiva local no anastomótica resecada. Por lo tanto, la vigilancia debe continuarse cuidadosamente considerando el mal pronóstico de los pacientes con recurrencia anastomótica. Consulte Video Resumen en http://links.lww.com/DCR/C92 . (Traducción-Dr. Jorge Silva Velazco ).
Asunto(s)
Neoplasias Colorrectales , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Metástasis Linfática , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Recurrencia , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patologíaRESUMEN
BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that converts tryptophan to kynurenine. IDO1 expression is found not only in tumor cells but also in immune cells and is associated with tumor proliferation and immune responses. IDO1 inhibitors and radiation may cooperatively suppress tumor proliferation through the alterations in the Wnt/ß-catenin pathway, cell cycle, and immune response. We investigated the antitumor effects of combination therapy of an IDO1 inhibitor, 1-methyl tryptophan (1-MT), and radiation on colorectal cancer. METHODS: In vitro experiments were conducted using human and murine colon cancer cell lines (HCT116, HT-29, and Colon26). Cell growth inhibition was assessed using a MTS assay and Clonogenic assay. Cells were cultured for 48 h with or without 500 µM 1-MT after exposure to radiation (4 Gy). Cell cycle effects and modulation of Wnt/ß-catenin pathway were evaluated using western blot analysis, flow cytometry, RT-PCR. Subcutaneous Colon26 tumors in BALB/c mice were treated by oral 1-MT (6 mg/mL) for 2 weeks and/or local radiation (10 Gy/10 fr). Bromodeoxyuridine (BrdU) incorporation in tumor cells and expression of differentiation markers of immune cells were evaluated using immunohistochemistry. RESULTS: 1-MT and a small interfering RNA against IDO1 suppressed proliferation of all cell lines, which was rescued by kynurenine. Clonogenic assay showed that administration of 1-MT improved radiosensitivity by suppressing the Wnt/ß-catenin pathway activated by radiation and enhancing cell cycle arrest induced by radiation. Combination therapy showed a further reduction in tumor burden compared with monotherapies or untreated control, inducing the highest numbers of intratumoral CD3 + and CD8 + T cells and the lowest numbers of Foxp3 + and BrdU-positive tumor cells. CONCLUSIONS: The combination of 1-MT and radiation suppressed colon cancer cells in vitro and in vivo via multiple mechanisms.