N6-methyladenosine modification of a parvovirus-encoded small noncoding RNA facilitates viral DNA replication through recruiting Y-family DNA polymerases.

Human bocavirus 1 (HBoV1) is a human parvovirus that causes lower respiratory tract infections in young children. It contains a single-stranded (ss) DNA genome of ~5.5 kb that encodes a small noncoding RNA of 140 nucleotides known as bocavirus-encoded small RNA (BocaSR), in addition to viral proteins. Here, we determined the secondary structure of BocaSR in vivo by using DMS-MaPseq. Our findings reveal that BocaSR undergoes N6-methyladenosine (m6A) modification at multiple sites, which is critical for viral DNA replication in both dividing HEK293 cells and nondividing cells of the human airway epithelium. Mechanistically, we found that m6A-modified BocaSR serves as a mediator for recruiting Y-family DNA repair DNA polymerase (Pol) η and Pol κ likely through a direct interaction between BocaSR and the viral DNA replication origin at the right terminus of the viral genome. Thus, this report represents direct involvement of a viral small noncoding RNA in viral DNA replication through m6A modification.

Noncanonical PDK4 action alters mitochondrial dynamics to affect the cellular respiratory status.

Dynamic regulation of mitochondrial morphology provides cells with the flexibility required to adapt and respond to electron transport chain (ETC) toxins and mitochondrial DNA-linked disease mutations, yet the mechanisms underpinning the regulation of mitochondrial dynamics machinery by these stimuli is poorly understood. Here, we show that pyruvate dehydrogenase kinase 4 (PDK4) is genetically required for cells to undergo rapid mitochondrial fragmentation when challenged with ETC toxins. Moreover, PDK4 overexpression was sufficient to promote mitochondrial fission even in the absence of mitochondrial stress. Importantly, we observed that the PDK4-mediated regulation of mitochondrial fission was independent of its canonical function, i.e., inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC). Phosphoproteomic screen for PDK4 substrates, followed by nonphosphorylatable and phosphomimetic mutations of the PDK4 site revealed cytoplasmic GTPase, Septin 2 (SEPT2), as the key effector molecule that acts as a receptor for DRP1 in the outer mitochondrial membrane to promote mitochondrial fission. Conversely, inhibition of the PDK4-SEPT2 axis could restore the balance in mitochondrial dynamics and reinvigorates cellular respiration in mitochondrial fusion factor, mitofusin 2-deficient cells. Furthermore, PDK4-mediated mitochondrial reshaping limits mitochondrial bioenergetics and supports cancer cell growth. Our results identify the PDK4-SEPT2-DRP1 axis as a regulator of mitochondrial function at the interface between cellular bioenergetics and mitochondrial dynamics.

Identification of host essential factors for recombinant AAV transduction of the polarized human airway epithelium.

IMPORTANCE: The essential steps of successful gene delivery by recombinant adeno-associated viruses (rAAVs) include vector internalization, intracellular trafficking, nuclear import, uncoating, double-stranded (ds)DNA conversion, and transgene expression. rAAV2.5T has a chimeric capsid of AAV2 VP1u and AAV5 VP2 and VP3 with the mutation A581T. Our investigation revealed that KIAA0319L, the multiple AAV serotype receptor, is not essential for vector internalization but remains critical for efficient vector transduction to human airway epithelia. Additionally, we identified that a novel gene WDR63, whose cellular function is not well understood, plays an important role in vector transduction of human airway epithelia but not vector internalization and nuclear entry. Our study also discovered the substantial transduction potential of rAAV2.5T in basal stem cells of human airway epithelia, underscoring its utility in gene editing of human airways. Thus, the knowledge derived from this study holds promise for the advancement of gene therapy in the treatment of pulmonary genetic diseases.

Comparison of EPIC Versus HIPEC in the Treatment of Colorectal Peritoneal Metastases and Appendix Tumors Using Inverse Probability of Treatment Weighting.

BACKGROUND: The selection of hyperthermic intraperitoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) for peritoneal metastases from colorectal cancer or appendiceal neoplasms following cytoreductive surgery (CRS) depends on the surgeon's discretion. This study was designed to compare postoperative and oncologic outcomes of HIPEC and EPIC using inverse probability of treatment weighting (IPTW). METHODS: This study included 175 patients who received HIPEC or EPIC following CRS at a single tertiary university hospital between December 1999 and December 2020. Inverse probability of treatment weighting analysis was performed to control for pretreatment characteristics between the two groups. Multivariate analysis was performed to determine factors associated with postoperative and survival outcomes. RESULTS: After IPTW, no significant differences in baseline demographics and tumor characteristics were observed between the two groups. The HIPEC group had a significantly longer operation time than the EPIC group. The EPIC group showed a significantly higher postoperative mortality rate than the HIPEC group. Operation time (odds ratio [OR] 1.01; 95% confidence interval [CI] 1.01-1.02; p < 0.001), bowel anastomosis (OR 7.25; 95% CI 1.16-45.2; p = 0.034), neoadjuvant chemotherapy (OR 7.62; 95% CI 1.85-31.4; p = 0.005), and EPIC (OR 8.76; 95% CI 2.16-35.5; p = 0.002) were independent risk factors for major surgical complications. No association was observed between intraperitoneal chemotherapy type and major hematologic toxicity, overall survival, progression-free survival, or peritoneal progression-free survival. CONCLUSIONS: EPIC was a risk factor for major surgical complications. Survival outcomes were similar between the two types of intraperitoneal chemotherapy.

Sequential Lateral Lymphatic Metastasis Shows Similar Oncologic Outcomes to Upward Spread in Advanced Rectal Cancer After Preoperative Chemoradiotherapy.

BACKGROUND: Whether lateral pelvic node metastasis should be considered as a regional or systemic disease is a long-standing debate. Although previous Japanese studies have considered it to be locoregional disease, Western countries consider it a systemic disease and do not perform lateral pelvic node dissection after preoperative chemoradiotherapy. OBJECTIVE: To evaluate whether lateral pelvic node metastasis is a systemic or regional disease that is amenable to curative resection. DESIGN: Retrospective analysis of a prospectively collected database. SETTING: This study was conducted at a tertiary cancer center. PATIENTS: There were 616 consecutive patients who underwent curative total mesorectal excision alone or with lateral pelvic node dissection after preoperative chemoradiotherapy for locally advanced rectal cancer between 2011 and 2019. MAIN OUTCOME MEASURES: Three-year disease-free and overall survival. RESULTS: A total of 360 patients underwent total mesorectal excision, and 160 patients underwent total mesorectal excision with lateral pelvic node dissection. There was no difference in the 3-year disease-free survival (DFS; p = 0.844) or overall survival rates ( p = 0.921) between the groups. Patients with lateral pelvic node metastasis showed DFS similar to those with perirectal lymph node metastasis in the total mesorectal excision group. In a subgroup analysis, patients with internal iliac pelvic node metastasis showed a disease-free survival comparable to those with perirectal node involvement, and patients with other lateral pelvic node metastasis showed a DFS similar to those with intermediate node involvement. In the lateral pelvic node dissection group, the lateral pelvic node metastatic rate was 32.5%. On multivariate analysis, fewer than 8 of the unilateral harvested lateral pelvic nodes and advanced ypT stage were significantly associated with poor disease-free survival. LIMITATION: The retrospective design. CONCLUSIONS: Lateral lymphatic metastasis showed oncologic outcomes similar to those of upward spread, especially perirectal lymph nodes metastasis. Large cohort studies with long-term follow-up are required to confirm these results. See Video Abstract . LAS METSTASIS LINFTICAS SECUENCIALES LATERALES MUESTRAN RESULTADOS ONCOLGICOS SIMILARES EN LA PROPAGACIN ASCENDENTE DEL CNCER RECTAL AVANZADO DESPUS DE LA RADIOQUIMIOTERAPIA PREOPERATORIA: ANTECEDENTES:Es un debate muy antiguo si las metástasis en los ganglios pélvicos laterales deben considerarse una enfermedad regional o sistémica. Si bien estudios japoneses anteriores las consideran como una enfermedad locorregional, en los países de occidente se las considera como una enfermedad sistémica por la cual no se realiza disección de ganglios pélvicos laterales después de una radioquimioterapia preoperatoria.OBJETIVOS:Evaluar si la metástasis en los ganglios pélvicos laterales se consideran como enfermedad sistémica o enfermedad regional susceptible de resección curativa.DISEÑO:Análisis retrospectivo de una base de datos recopilada prospectivamente.AJUSTE:Este estudio se realizó en un centro oncológico terciario.PACIENTES:616 pacientes consecutivos se sometieron a excisión total del mesorrecto curativa sola o con disección de los ganglios pélvicos laterales después de radioquimioterapia preoperatoria en casos de cáncer de recto localmente avanzado entre 2011 y 2019.PRINCIPALES MEDIDAS DE RESULTADO:Sobrevida global y libre de enfermedad a 3 años.RESULTADOS:Un total de 360 pacientes se sometieron a excisión total del mesorrecto y 160 pacientes se sometieron a excisión total del mesorrecto con disección de ganglios pélvicos laterales.No hubo diferencias en la sobrevida libre de enfermedad a 3 años (p = 0,844) ni en las tasas de sobrevida general (p = 0,921) entre los grupos. Los pacientes con metástasis en los ganglios pélvicos laterales mostraron una sobrevida libre de enfermedad similar a aquellos con metástasis en los ganglios linfáticos perirrectales que se encontraban en el grupo de excisión total del mesorrecto.En el análisis de subgrupos, los pacientes con metástasis en los ganglios pélvicos ilíacos internos mostraron una sobrevida libre de enfermedad comparable a aquellos con afección de los ganglios perirrectales y los pacientes con otras metástasis en los ganglios pélvicos laterales mostraron una sobrevida libre de enfermedad similar a aquellos con afección de los ganglios intermedios.En el grupo de disección de los ganglios pélvicos laterales, la tasa de metástasis en dichos ganglios fué del 32,5%. En el análisis multivariado, < de 8 ganglios pélvicos laterales resecados unilateralmente y el estadio ypT avanzado se asociaron significativamente con una menor sobrevida libre de enfermedad.LIMITACIÓN:El diseño retrospectivo del estudio.CONCLUSIONES:Las metástasis linfáticas laterales mostraron resultados oncológicos similares a la diseminación ascendente, especialmente las metástasis en los ganglios linfáticos perirrectales. Se requieren grandes estudios de cohortes con seguimiento a largo plazo para confirmar estos resultados. (Traducción-Dr. Xavier Delgadillo ).

Long-term Complications of Laparoscopic or Robotic Lateral Pelvic Node Dissection After Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: Patients with rectal cancer who underwent lateral pelvic node dissection might be at a higher risk of postoperative complications derived from technical complexity. However, little is known regarding the long-term complications after lateral pelvic node dissection. OBJECTIVES: The study aimed to investigate the long-term complications of preoperative chemoradiotherapy, followed by total mesorectal excision with lateral pelvic node dissection for locally advanced rectal cancers. DESIGN: A retrospective analysis of a prospectively collected database. SETTINGS: This study was conducted in a tertiary cancer center. PATIENTS: Patients with rectal cancer who underwent total mesorectal excision with lateral pelvic node dissection after preoperative chemoradiotherapy between 2011 and 2019 were analyzed. All operations were performed via a laparoscopic or robotic approach. MAIN OUTCOME MEASURES: Long-term complications were defined as adverse events that persisted or newly appeared ≥90 days after surgery and could be related to the surgery. RESULTS: A total of 164 patients underwent total mesorectal excision with lateral pelvic node dissection after preoperative chemoradiotherapy. Short-term and long-term complication rates were 36.0% and 36.6%, respectively. Lymphocele was the most common long-term complication (17.7% of patients), and 11.6% had anastomotic leakage with chronic sinus. Of the patients with long-term complications, 20.7% of patients needed readmission for treatment. Of the 29 patients with lymphocele, 13 (41.0%) experienced spontaneous absorption and 11 (37.9%) required surgical or percutaneous catheter drainage or antibiotics use. Multivariate analysis showed pathologic pelvic node metastases ( p = 0.008), and a higher number of unilateral harvested pelvic nodes ( p = 0.001) were significantly associated with long-term complications. At the last follow-up (median duration of 43 months), 15.9% of patients had unresolved complications. LIMITATIONS: The retrospective design. CONCLUSIONS: Patients undergoing lateral pelvic node dissection experienced a higher frequency of long-term complications, but half of them had asymptomatic lymphoceles, most of which resolved spontaneously. However, further efforts should be paid to reduce anticipated complications related to lateral pelvic node dissection. See Video Abstract . COMPLICACIONES A LARGO PLAZO DE LA DISECCIN DE LOS GANGLIOS LIFTICOS PLVICOS LATERALES LAPAROSCPICA O ROBTICA DESPUS DE LA QUIMIORRADIOTERAPIA PREOPERATORIA CONTRA EL CNCER DEL RECTO LOCALMENTE AVANZADO: ANTECEDENTES:Los pacientes con cáncer del recto sometidos a disección ganglionar linfática pélvica lateral podrían tener mayor riesgo de complicaciones postoperatorias derivadas de la complejidad técnica. Sin embargo, se sabe poco sobre las complicaciones a largo plazo después de la disección de los ganglios linfáticos pélvicos laterales.OBJETIVOS:Investigar las complicaciones a largo plazo de la quimiorradioterapia preoperatoria, seguida de escisión mesorrectal total con disección de los ganglios linfáticos pélvicos laterales contra el cáncer de recto localmente avanzado.DISEÑO:Un análisis retrospectivo de una base de datos recopilada prospectivamente.AJUSTES:Este estudio se llevó a cabo en un centro oncológico terciario.PACIENTES:Se analizaron pacientes con cáncer de recto que se sometieron a escisión mesorrectal total con disección de ganglios linfáticos pélvicos laterales después de quimiorradioterapia preoperatoria entre 2011 y 2019. Todas las operaciones se realizaron mediante abordaje laparoscópico o robótico.PRINCIPALES MEDIDAS DE RESULTADO:Las complicaciones a largo plazo se definieron como eventos adversos que persistieron o aparecieron recientemente ≥ 90 días después de la cirugía y podrían estar relacionados con la cirugía.RESULTADOS:Un total de 164 pacientes se sometieron a escisión mesorrectal total con disección de los ganglios linfáticos pélvicos laterales después de quimiorradioterapia preoperatoria. Las tasas de complicaciones a corto y largo plazo fueron del 36,0% y 36,6%, respectivamente. El linfocele fue la complicación a largo plazo más común (17,7% de los pacientes) y el 11,6% tuvo fuga anastomótica con seno crónico. De los pacientes con complicaciones a largo plazo, el 20,7% de los pacientes necesitaron reingreso para recibir tratamiento. De 29 pacientes con linfocele, 13 (41,0%) experimentaron absorción espontánea y 11 (37,9%) requirieron drenaje quirúrgico o percutáneo con catéter o uso de antibióticos. El análisis multivariado mostró metástasis patológicas en los ganglios linfáticos pélvicos ( p = 0,008) y un mayor número de ganglios pélvicos extraídos unilateralmente ( p = 0,001) se asociaron significativamente con complicaciones a largo plazo. En el último seguimiento (mediana de 43 meses), el 15,9% de los pacientes tuvieron complicaciones no resueltas.LIMITACIÓN:El diseño retrospectivo.CONCLUSIONES:Los pacientes sometidos a disección de ganglios pélvicos linfáticos laterales experimentaron una mayor frecuencia de complicaciones a largo plazo, pero la mitad de ellos tuvieron linfoceles asintomáticos, la mayoría de los cuales se resolvieron espontáneamente. Sin embargo, se deben realizar mayores esfuerzos para reducir las complicaciones previstas relacionadas con la disección de los ganglios linfáticos pélvicos laterales. (Traducción-Dr. Aurian Garcia Gonzalez ).

Comparison of Laparoscopic Versus Robot-Assisted Surgery for Rectal Cancers: The COLRAR Randomized Controlled Trial.

OBJECTIVE: To evaluate whether robotic for middle or low rectal cancer produces an improvement in surgical outcomes compared with laparoscopic surgery in a randomized controlled trial (RCT). BACKGROUND: There is a lack of proven clinical benefit of robotic total mesorectal excision (TME) compared with a laparoscopic approach in the setting of multicenter RCTs. METHODS: Between July 2011 and February 2016, patients diagnosed with an adenocarcinoma located <10 cm from the anal verge and clinically rated T1-4aNxM0 were enrolled. The primary outcome was the completeness of TME assessed by a surgeon and a pathologist. RESULTS: The RCT was terminated prematurely because of poor accrual of data. In all, 295 patients were assigned randomly to a robot-assisted TME group (151 in R-TME) or a laparoscopy-assisted TME group (144 in L-TME). The rates of complete TME were not different between groups (80.7% in R-TME, 77.1% in L-TME). Pathologic outcomes including the circumferential resection margin and the numbers of retrieved lymph nodes were not different between groups. In a subanalysis, the positive circumferential resection margin rate was lower in the R-TME group (0% vs 6.1% for L-TME; P =0.031). Among the recovery parameters, the length of opioid use was shorter in the R-TME group ( P =0.028). There was no difference in the postoperative complication rate between the groups (12.0% for R-TME vs 8.3% for L-TME). CONCLUSIONS: In patients with middle or low rectal cancer, robotic-assisted surgery did not significantly improve the TME quality compared with conventional laparoscopic surgery (ClinicalTrial.gov ID: NCT01042743).

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial).

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.

Oncological impact of intraperitoneal chemotherapy after cytoreductive surgery for patients with colorectal peritoneal metastasis: A bi-institutional retrospective analysis.

BACKGROUND AND OBJECTIVES: There is a paucity of evidence on the value of intraperitoneal chemotherapy (IPC) following cytoreductive surgery (CRS) for colorectal peritoneal metastasis. This study aimed to evaluate the association between mitomycin C-IPC and survival outcomes following CRS. METHODS: The institutional databases of two tertiary hospitals were reviewed to identify patients who underwent CRS for colorectal peritoneal metastasis. The outcomes of patients who underwent CRS without IPC were compared with those of patients who underwent CRS plus early postoperative intraperitoneal chemotherapy (EPIC) or CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC). The primary endpoints were cancer-specific survival (CSS), progression-free survival (PFS), and peritoneal PFS (P-PFS). RESULTS: In 149 patients with peritoneal metastasis alone, EPIC and HIPEC use was significantly associated with better CSS, PFS, and P-PFS in the multivariate analysis. CSS was also significantly associated with perioperative systemic chemotherapy. Among 42 patients with both peritoneal and extraperitoneal metastases, CSS was independently related to the completeness of cytoreduction score, location of extraperitoneal metastasis, and grade 3-4 complications. CONCLUSIONS: Mitomycin C-IPC after CRS was associated with better survival outcomes than CRS alone in patients with resectable peritoneal metastasis of colorectal cancer. This study found that IPC had beneficial effects regarding P-PFS in patients with both peritoneal and extraperitoneal metastases.

Robotic and laparoscopic salvage lateral pelvic node dissection for the treatment of recurrent rectal cancer.

BACKGROUND: The lateral pelvic sidewall is a major site of local recurrence after radical resection of rectal cancer. Salvage lateral pelvic node dissection (LPND) may be the only way to eliminate recurrent lateral pelvic nodes (LPNs). This study aimed to describe the technical details of robotic and laparoscopic salvage LPND and assess the short-term clinical and oncological outcomes in patients with recurrent LPNs who underwent salvage LPND by a minimally invasive approach for curative intent. METHODS: Between September 2010 and 2019, 36 patients who underwent salvage surgery for LPN recurrence were retrospectively analyzed from a prospectively maintained database. Patients' characteristics, index operation, MRI findings, and perioperative and pathological outcomes were analyzed. RESULTS: Eleven and 14 patients underwent robotic and laparoscopic salvage LPND, respectively. Eight patients (32.0%) underwent a combined salvage operation for resectable extra-pelvic sidewall metastases. There were four cases of open-conversion during the laparoscopic approach due to uncontrolled bleeding of iliac vessels. In these patients, metastatic LPNs were suspected of iliac vessel invasion and were found to be larger in size (median 15 mm; range 12-20) than that in patients who underwent successful LPND using the minimally invasive approach (median 10 mm; range 5-20). The median number of metastatic LPNs and harvested LPNs was 1 (range 0-3) and 6 (range 1-16), respectively. Six patients (24.0%) experienced postoperative complications including lymphoceles and voiding difficulties. During the follow-up (median 44.6 months; range 24.0-87.7), eight patients developed recurrences, mainly the lung and para-aortic lymph nodes, and one patient developed pelvic sidewall recurrence after laparoscopic salvage LPND. The 3-year disease-free survival and overall survival after salvage LPND were 66.4% and 79.2%, respectively. CONCLUSIONS: Robotic and laparoscopic salvage LPND for recurrent LPNs are safe and feasible with favorable short-term surgical outcomes. However, the surgical approach should be carefully chosen in patients with large-sized and invasive recurrent LPNs.

Lef-1 controls cell cycle progression in airway basal cells to regulate proliferation and differentiation.

The mammalian airways are lined by a continuous epithelial layer that is maintained by diverse populations of resident multipotent stem cells. These stem cells are responsible for replenishing the epithelium both at homeostasis and following injury, making them promising targets for stem cell and genetic-based therapies for a variety of respiratory diseases. However, the mechanisms that regulate when and how these stem cells proliferate, migrate, and differentiate remains incompletely understood. Here, we find that the high mobility group (HMG) domain transcription factor Lef-1 regulates proliferation and differentiation of mouse tracheal basal cells. We demonstrate that conditional deletion of Lef-1 stalls basal cell proliferation at the G1/S transition of the cell cycle, and that Lef-1 knockout cells are unable to maintain luminal tracheal cell types in long-term air-liquid interface culture. RNA sequencing analysis revealed that Lef-1 knockout (Lef-1KO) results in downregulation of key DNA damage response and cell cycle progression genes, including the kinase Chek1. Furthermore, chemical inhibition of Chek1 is sufficient to stall basal cell self-renewal in a similar fashion as Lef-1 deletion. Notably, the cell cycle block imposed by Lef-1KO in vitro is transient and basal cells eventually compensate to proliferate normally in a Chek1-independent manner. Finally, Lef-1KO cells were unable to fully regenerate tracheal epithelium following injury in vivo. These findings reveal that Lef-1 is essential for proper basal cell function. Thus, modulating Lef-1 function in airway basal cells may have applications in regenerative medicine.

Stepwise Improvement of Surgical Quality in Robotic Lateral Pelvic Node Dissection: Lessons From 100 Consecutive Patients With Locally Advanced Rectal Cancer.

BACKGROUND: Lateral pelvic node dissection has significant technical difficulty and a high incidence of surgical morbidity. A steep learning curve is anticipated in performing lateral pelvic node dissection. However, no study has previously analyzed the learning curve and surgical skill acquisition for this complex procedure. OBJECTIVES: We aimed to evaluate the learning process for performing robotic total mesorectal excision with lateral pelvic node dissection in patients with rectal cancer. DESIGN: This is a retrospective analysis of a prospectively collected database. SETTING: This study was conducted at a tertiary cancer center. PATIENTS: A total of 100 patients who underwent robotic total mesorectal excision with lateral pelvic node dissection between 2011 and 2017 were included. MAIN OUTCOME MEASURES: A cumulative sum analysis was calculated based on the number of unilateral retrieved lateral pelvic nodes. Operative time, estimated bloodloss, lateral pelvic node metastatic rate, postoperative morbidities, and local recurrence were also analyzed. RESULTS: Cumulative sum modeling suggested 4 learning phases: learning I (33 patients), learning II (19 patients), consolidation (30 patients), and competence (18 patients). In the consolidation and competence phases, we adopted fluorescence imaging and standardized the surgical procedure on the basis of anatomical planes. The competence phase had the greatest number of unilateral retrieved lateral pelvic nodes (12.8 vs 4.9, 8.2, and 10.4; p < 0.001). Urinary complications, including urinary retention and postoperative α-blocker usage, were more frequently observed in learning phase I than in the competence phase (39.4% vs 16.7%, p = 0.034). During the median follow-up of 44.2 months, local recurrence in the pelvic sidewall was observed in 4 patients from learning phase I and in 1 patient from learning phase II. LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Completeness of the lateral pelvic node dissection procedure increased with the surgeon's experience and as new imaging systems and surgical technique standardization were implemented. Further studies are warranted to determine the oncologic outcomes associated with each phase. See Video Abstract at http://links.lww.com/DCR/B774. MEJORA GRADUAL DE LA CALIDAD QUIRRGICA EN LA DISECCIN LINFTICA PLVICA LATERAL ROBTICA LECCIONES DE PACIENTES CONSECUTIVOS CON CNCER DE RECTO LOCALMENTE AVANZADO: ANTECEDENTES:La disección linfática pélvica lateral tiene una dificultad técnica significativa y una alta incidencia de morbilidad quirúrgica. Se prevé una curva de aprendizaje muy pronunciada al realizar la disección linfática pélvica lateral. Sin embargo, ningún estudio ha analizado previamente la curva de aprendizaje y la adquisición de habilidades quirúrgicas para este procedimiento.OBJETIVOS:Nuestro objetivo fue evaluar el proceso de aprendizaje para realizar la escisión total de mesorrecto robótica con disección linfática pélvica lateral en pacientes con cáncer de recto.DISEÑO:Este es un análisis retrospectivo de una base de datos recopilada prospectivamente.AJUSTE:Este estudio se realizó en un centro oncológico terciario.PACIENTES:Un total de 100 pacientes fueron sometidos a escisión total de mesorrecto robótica con disección linfática pélvica lateral entre 2011 y 2017.PRINCIPALES MEDIDAS DE DESENLACE:Se calculó un análisis de suma acumulativa basado en el número unilateral de ganglios pélvicos laterales recuperados. También se analizaron el tiempo operatorio, la pérdida de sangre estimada, la tasa de metástasis ganglionares pélvicas laterales, las morbilidades postoperatorias y la recidiva local.RESULTADOS:El modelado total acumulativo sugirió cuatro fases de aprendizaje: aprendizaje I (33 pacientes), aprendizaje II (19 pacientes), consolidación (30 pacientes) y competencia (18 pacientes). En las fases de consolidación y competencia, adoptamos imágenes de fluorescencia y estandarizamos el procedimiento quirúrgico basado en planos anatómicos, respectivamente. La fase de competencia tuvo el mayor número de ganglios pélvicos laterales recuperados unilateralmente (12,8 frente a 4,9, 8,2 y 10,4; p < 0,001). Las complicaciones urinarias, incluida la retención urinaria y el uso posoperatorio de bloqueadores beta, se observaron con más frecuencia en la fase de aprendizaje I que en la fase de competencia (39,4% frente a 16,7%, p = 0,034). Durante la mediana de seguimiento de 44,2 meses, se observó una recidiva local en la pared lateral pélvica en cuatro pacientes de la fase de aprendizaje I y en un paciente de la fase de aprendizaje II.LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo.CONCLUSIÓNES:La completitud del procedimiento de disección linfática pélvica lateral aumentó con la experiencia del cirujano y a medida que se implementaron nuevos sistemas de imágenes y estandarización de técnicas quirúrgicas. Se necesitan más estudios para determinar los resultados oncológicos asociados con cada fase. Consulte Video Resumen en http://links.lww.com/DCR/B774.

Laparoscopic versus open surgery for left flexure colon cancer: A propensity score matched analysis from an international cohort.

AIM: Surgical treatment of splenic flexure cancer (SFC) still presents some debated issues, including the role of laparoscopic surgery. The literature is based on small single-centre series, while randomized controlled studies comparing open and laparoscopic treatment for colon cancer exclude SFC. This study aimed to determine the role of laparoscopic surgery in the treatment of SFC, comparing short- and long-term outcomes with open surgery. METHOD: This was an international multicentre retrospective cohort study that analysed patients from 10 tertiary referral centres. From a cohort of 641 cases, 484 patients with Stage I-III SFC submitted to elective surgery with curative intent were selected. After 1:1 propensity score matching, 130 patients in the laparoscopic group (LapGroup) were compared with 130 patients in the open surgery group (OpenGroup). RESULTS: After propensity score matching, the two groups were comparable for demographic and clinical parameters. OpenGroup presented a higher incidence of overall (P = 0.02) and surgery-related complications (P = 0.05) but a similar rate of severe complications (P = 0.75). Length of stay was notably shorter in the LapGroup (P = 0.001). Overall (P = 0.793) as well as cancer-specific survival (P = 0.63) did not differ between the two groups. CONCLUSIONS: Elective laparoscopic surgery for Stage I-III SFC is feasible and associated with improved short-term postoperative outcomes compared to open surgery. Moreover, laparoscopic surgery appears to provide excellent long-term cancer outcomes.

Comparison of the Analgesic Efficacy of Opioid-Sparing Multimodal Analgesia and Morphine-Based Patient-Controlled Analgesia in Minimally Invasive Surgery for Colorectal Cancer.

BACKGROUND: A multimodal analgesia (MMA) protocol has shown the effect of postoperative pain control and reduced the postoperative opioid consumption. However, it was questionable whether MMA could replace opioid-based patient-controlled analgesia (PCA) for postoperative pain control. Therefore, this study aimed to investigate whether an MMA protocol is non-inferior to opioid-based PCA for pain management after a minimally invasive colorectal cancer surgery. METHODS: A randomized, open-label, non-inferiority clinical trial was conducted on patients undergoing laparoscopic or robotic resection of colorectal cancer. The patients were randomly assigned to either the PCA or MMA group. The MMA protocol included pregabalin, tramadol, wound infiltration, and transversus abdominis plane block. The primary outcome was the numeric rating scale (NRS) score for pain at rest 24 h postoperatively. RESULTS: Ninety-seven patients were included in the intention-to-treat analysis. The mean difference in NRS score at rest at 24 h was 0.25 (95% confidence interval, - 0.61 to 1.11). This result demonstrated the non-inferiority of MMA to PCA in our non-inferiority margin (- 1). Compared with the PCA group, the median remifentanil dose (996 vs. 654 µg; p < 0.001) and time in the post-anesthesia care unit (35 vs. 25 min; p < 0.001) were significantly less in the MMA group. CONCLUSIONS: Our MMA protocol successfully controlled postoperative pain and was non-inferior to morphine-based PCA based on patient-reported pain intensity, with no significant increase in adverse events. These results will help construct a strategy to reduce conventional opioid prescriptions for pain management after a minimally invasive colorectal cancer surgery. Trial Registration Number Trial Registration Clinical Research Information Service Identifier: KCT0002593.

Robot Surgery Shows Similar Long-term Oncologic Outcomes as Laparoscopic Surgery for Mid/Lower Rectal Cancer but Is Beneficial to ypT3/4 After Preoperative Chemoradiation.

BACKGROUND: The long-term oncologic efficacy of robotic surgery for patients with rectal cancer is unknown. OBJECTIVE: The aim of the study was to investigate survival outcomes of robotic total mesorectal excision for mid/low rectal cancer compared with those of laparoscopic surgery. DESIGN: We performed a single-center retrospective analysis. SETTING: The data of a tertiary academic institution was reviewed. PATIENTS: A total of 705 patients underwent laparoscopic (n = 415) or robotic (n = 118) low anterior resection for stage I to III mid/low rectal cancer. A total of 118 patients in each group were selected from the original data set by using propensity score matching. MAIN OUTCOME MEASURES: The main outcomes were 5-year disease-free survival, distant recurrence, and local recurrence. RESULTS: The 2 groups were balanced in terms of basic characteristics, perioperative treatment, and pathological stage. The 5-year disease-free survival rate was 80.5% in the laparoscopic group and 87.6% in the robotic group (p = 0.118). The 5-year distant recurrence rate and local recurrence rate were 19.0% and 4.2% in the laparoscopic group and 10.0% and 3.7% in the robotic group (p = 0.048 and p = 0.846). In a subgroup of patients who received preoperative chemoradiation and had ypT3/4 tumors, the 5-year distant recurrence and local recurrence rates were 44.8% and 5.0% in the laparoscopic group and 9.8% and 9.8% in the robotic group (p = 0.014 and p = 0.597). LIMITATIONS: The retrospective nature of the study, potential selection bias with distinct demographics between the groups, and relatively small number of cases are limitations. CONCLUSIONS: Robotic surgery for mid/low rectal cancer shows similar long-term oncologic outcomes with laparoscopic surgery but is beneficial to a certain group of patients with advanced rectal cancer with poor response to neoadjuvant chemoradiation. Additional studies are required to confirm our results. See Video Abstract at http://links.lww.com/DCR/B546. LA CIRUGA ROBTICA MUESTRA RESULTADOS ONCOLGICOS A LARGO PLAZO SIMILARES A LA CIRUGA LAPAROSCPICA EN CASOS DE CNCER DE RECTO MEDIO / BAJO, PERO ES VENTAJOSA EN CASOS YPT POSTQUIMIORADIOTERAPIA PREOPERATORIA: ANTECEDENTES:Se desconoce la eficacia oncológica a largo plazo de la cirugía robótica en pacientes con cáncer de recto.OBJETIVO:La finalidad de nuestro estudio fue el investigar los resultados de supervivencia de la escisión mesorrectal total robótica en casos de cáncer de recto medio / bajo en comparación con los de la cirugía laparoscópica.DISEÑO:Realizamos un análisis retrospectivo mono-céntrico.AJUSTE:Se revisaron los datos de una institución académica terciaria.PACIENTES:705 pacientes fueron sometidos a resección anterior baja laparoscópica (n = 415) o robótica (n = 118) para cáncer de recto medio / bajo en estadio I-III. Se seleccionó un total de 118 pacientes en cada grupo del conjunto de datos original utilizando el emparejamiento por puntuación de propensión.RESULTADOS PRINCIPALES:Éstos fueron, la supervivencia libre de enfermedad a 5 años, la recurrencia a distancia y la recurrencia local.RESULTADOS:Los dos grupos estaban equilibrados en cuanto a características básicas, tratamiento péri-operatorio y estadío patológico. La tasa de sobrevida libre de enfermedad a 5 años fue del 80,5% en el grupo laparoscópico y del 87,6% en el grupo robótico (p = 0,118). La tasa de recurrencia a distancia a 5 años y la tasa de recurrencia local fueron 19,0% y 4,2% en el grupo laparoscópico y 10,0% y 3,7% en el grupo robótico, respectivamente (p = 0,048 y p= 0,846). En el subgrupo de pacientes que recibieron quimio-radioterapia pré-operatoria y tenían tumores ypT3-4, las tasas de recidiva a distancia a 5 años y recidiva local fueron 44,8% y 5,0% en el grupo laparoscópico y 9,8% y 9,8% en el grupo robótico, respectivamente (p = 0.014 y p = 0.597).LIMITACIONES:La naturaleza retrospectiva del estudio, el posible sesgo en la selección con datos demográficos distintos entre los grupos y un número relativamente pequeño de casos son limitaciones importantes.CONCLUSIONES:La cirugía robótica para el cáncer de recto medio / bajo muestra resultados oncológicos a largo plazo similares con la cirugía laparoscópica, pero es mas beneficiosa en ciertos grupos de cáncer de recto avanzado con mala respuesta a la quimio-radioterapia neoadyuvante. Se requieren más estudios para confirmar nuestros resultados. Consulte Video Resumen en http://links.lww.com/DCR/B546.).

Prognostic Value of Venous Invasion Detected by Elastin Stain May Surpass Lymph Node Status in Colon Cancer.

BACKGROUND: Venous invasion is a poor prognostic factor in colon cancer but is often underreported with significant variability. OBJECTIVES: We aimed to determine the impact of an elastin stain on venous invasion detection in colon cancer and evaluate the value of venous invasion in predicting disease recurrence in combination with lymph node status and other prognostic factors. DESIGN: This is a retrospective analysis of a prospectively collected database. SETTING: This study was conducted at a tertiary cancer center. PATIENTS: A total of 418 patients who underwent curative resection for stage I to III colon cancer and routinely adopted an elastin stain were evaluated. MAIN OUTCOME MEASURES: Venous invasion detection rate after adopting elastin stain, prognostic factors influencing disease recurrences by multivariate Cox regression models, and survival were measured. The zones of lymph node metastasis were defined as LNZ1, LNZ2, and LNZ3, corresponding to metastases in the pericolic, intermediate, and apical nodes. RESULTS: Venous invasion detection rate increased from 11.3% to 35.4% compared with the previous period in which only hematoxylin and eosin stain was performed. Cox regression analysis showed venous invasion (HR, 3.856; 95% CI, 1.249-11.910; p = 0.019) and lymph node metastases (HR, 3.156; 95% CI, 1.094-9.108; p = 0.034) in all stages and LNZ 2, 3 (HR, 2.649; 95% CI, 1.244-5.640; p = 0.012) in stage III to be significantly associated with poor disease-free survival. When stratifying all patients by these 3 factors, patients with stage III [LNZ1/venous invasion (-)] had disease-free survival comparable with stage I, but significantly better disease-free survival than those with stage II [venous invasion (+)] (p = 0.018). Patients with stage II [venous invasion (+)] had better disease-free survival by using adjuvant chemotherapy (p < 0.001). LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Elastin stain contributed to a considerable increase in venous invasion detection. Venous invasion can be a powerful predictor of poor disease-free survival beyond lymph node metastases when limited to the pericolic area and is useful for deciding the use of adjuvant chemotherapy in stage II colon cancer. See Video Abstract at http://links.lww.com/DCR/B573. EL VALOR PRONSTICO DE LA INVASIN VENOSA DETECTADA POR LA TINCIN DE ELASTINA PUEDE SUPERAR EL ESTADO DE LOS GANGLIOS LINFTICOS EN EL CNCER DE COLON: ANTECEDENTES:Invasión venosa (IV) es un factor de mal pronóstico en el cáncer de colon, que frecuentemente no se informa con una variabilidad significativa.OBJETIVOS:Nuestro objetivo fue determinar el impacto de tinción de elastina en la detección de IV en el cáncer de colon y evaluar el valor de IV en la predicción de la recurrencia de la enfermedad en combinación con el estado de los ganglios linfáticos y otros factores pronósticos.DISEÑO:Este es un análisis retrospectivo de una base de datos recopilada prospectivamente.ENTORNO CLINICO:Este estudio se realizó en un centro oncológico de referencia de tercer nivel.PACIENTES:Se valoraron un total de 418 pacientes sometidos a resección curativa por cáncer de colon en estadio I-III utilizando de manera rutinaria una tinción de elastina.PRINCIPALES MEDIDAS DE VALORACION:Se midieron la tasa de detección de IV después de adoptar la tinción de elastina, los factores de pronóstico que influyen en las recurrencias de la enfermedad mediante modelos de regresión de Cox multivariados y la supervivencia. La zona de metástasis ganglionares se definió como, LNZ1, LNZ2 y LNZ3, correspondientes a las metástasis en los ganglios pericólicos, intermedios y apicales, respectivamente.RESULTADOS:La tasa de detección de IV aumentó de 11,3% a 35,4% en comparación con el período anterior en el que solo se realizó tinción con hematoxilina y eosina. El análisis de regresión de Cox mostró VI (razón de riesgo, 3.856; intervalo de confianza [IC] del 95%, 1.249-11.910, p = 0.019) y metástasis en los ganglios linfáticos (razón de riesgo, 3.156; IC del 95%, 1.094-9.108, p = 0.034) en todos los estadios y LNZ 2, 3 (cociente de riesgo, 2.649; IC del 95%, 1.244-5.640, p = 0.012) en el estadio III se asociaron significativamente con una pobre supervivencia libre de enfermedad. Al estratificar a todos los pacientes según estos tres factores, los pacientes con estadio III [LNZ1 / VI (-)] tuvieron una sobrevivencia sin enfermedad (SSE) comparable con el estadio I, pero una supervivencia libre de enfermedad significativamente mejor que aquellos con estadio II [VI (+)] (p = 0,018). Pacientes en estadío II [VI (+)] tuvieron una mejor supervivencia sin enfermedad mediante el uso de quimioterapia adyuvante (p <0,001).LIMITACIONES:Estudio limitado por su diseño retrospectivo.CONCLUSIÓN:La tinción de elastina contribuyó a un aumento considerable en la detección de IV. IV puede ser un poderoso predictor de supervivencia sin enfermedad deficiente más allá de las metástasis de los ganglios linfáticos cuando se limita al área pericólica y es útil para decidir el uso de quimioterapia adyuvante en el cáncer de colon en estadío II. Consulte Video Resumen en http://links.lww.com/DCR/B573. (Traducción-Dr. Adrian Ortega).

Initial experience of preoperative short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy for locally advanced rectal cancer.

PURPOSE: We analyzed the safety and feasibility of preoperative short-course radiotherapy (SCRT) followed by consolidation chemotherapy for patients with locally advanced rectal cancer (LARC). METHODS: From April 2018 to May 2019, 19 patients with LARC were treated with SCRT followed by three cycles of consolidation chemotherapy with leucovorin, fluorouracil, and oxaliplatin (FOLFOX6) before surgery. Adjuvant chemotherapy relied on oxaliplatin. Tumor response, patient compliance, and toxicities were analyzed. RESULTS: The median age was 60 years (range 44-71), and 16 of the patients were male. The median tumor height was 5 cm (range 0-9) from anal verge. All patients received a total dose of 25 Gy in five fractions. The number of cycles of FOLFOX6 before surgery was three in 17, four in one, five in one. Five patients required dose reductions in consolidation chemotherapy. The median interval between initiation of SCRT and surgery was 10.6 weeks (range 8.6-16.4). A pathologic complete response was seen in two patients (11%). Grade III toxicities to the preoperative treatment were seen in five patients (26%): diarrhea in two, a decreased white blood cell count in one, and anemia in two. Postoperative complications arising within 30 days developed in five patients (26%). During the median follow-up period of 20.4 months, there was no tumor recurrence. CONCLUSION: Preoperative SCRT followed by oxaliplatin-based consolidation chemotherapy showed acceptable toxicity and feasibility in patients with LARC. Prospective randomized trials are warranted to verify the efficacy and safety of this treatment strategy compared with conventional long-course concurrent chemoradiotherapy.

Analgesic efficacy of pre-emptive local wound infiltration plus laparoscopic-assisted transversus abdominis plane block versus wound infiltration in patients undergoing laparoscopic colorectal resection: results from a randomized, multicenter, single-blind, non-inferiority trial.

BACKGROUND: Transversus abdominis plane (TAP) block is considered a reliable locoregional technique for pain control after laparoscopic colorectal surgery. However, no clear benefit of TAP block over wound infiltration has been demonstrated by the current literature. This multicenter randomized clinical trial tested the non-inferiority of wound infiltration (WI) compared to WI plus laparoscopic-assisted TAP block (L-TAP). METHODS: All patients with colorectal cancer and diverticular disease scheduled for laparoscopic resection at the Division of General and Hepatobiliary Surgery, University of Verona Hospital Trust, Verona, Italy and at the Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University, Daegu, Korea, between April 2018 and March 2019 were considered for the trial. Patients were randomly allocated to either the WI group or the WI plus L-TAP group in a 1:1 allocation ratio. In total, 108 patients entered the study and 102 patients were analyzed; 50 patients received WI plus L-TAP and 52 patients received WI. The primary end point was the efficacy in pain control at 6 h measured according to Numeric Rating Scale (NRS). Secondary aims evaluated pain control at 12, 24, 48 and 72 h and other short-term results related to pain management. RESULTS: Estimation of pain intensity at 6 h was comparable between the two groups (p = 0.16) with a mean (95% CI) difference in pain scores of 0.94 (- 0.13 to 2.02). No differences in pain scores were observed at other interval times or considering analgesic consumption, return of bowel function, postoperative complications and length of hospital stay. CONCLUSION: This study suggests that adding TAP block to WI does not affect pain control, amount of analgesics and other short-term outcomes. TRIAL REGISTRATION: NCT03376048 ( https://www.clinicaltrials.gov ).

Prospective study of oncologic outcomes after laparoscopic modified complete mesocolic excision for non-metastatic right colon cancer (PIONEER study): study protocol of a multicentre single-arm trial.

BACKGROUND: The introduction of complete mesocolic excision (CME) with central vascular ligation (CVL) for right-sided colon cancer has improved the oncologic outcomes. Recently, we have introduced a modified CME (mCME) procedure that keeps the same principles as the originally described CME but with a more tailored approach. Some retrospective studies have reported the favourable oncologic outcomes of laparoscopic mCME for right-sided colon cancer; however, no prospective multicentre study has yet been conducted. METHODS: This study is a multi-institutional, prospective, single-arm study evaluating the oncologic outcomes of laparoscopic mCME for adenocarcinoma arising from the right side of the colon. A total of 250 patients will be recruited from five tertiary referral centres in South Korea. The primary outcome of this study is 3-year disease-free survival. Secondary outcome measures include 3-year overall survival, incidence of surgical complications, completeness of mCME, and distribution of metastatic lymph nodes. The quality of laparoscopic mCME will be assessed on the basis of photographs of the surgical specimen and the operation field after the completion of lymph node dissection. DISCUSSION: This is a prospective multicentre study to evaluate the oncologic outcomes of laparoscopic mCME for right-sided colon cancer. To the best of our knowledge, this will be the first study to prospectively and objectively assess the quality of laparoscopic mCME. The results will provide more evidence about oncologic outcomes with respect to the quality of laparoscopic mCME in right-sided colon cancer. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03992599 (June 20, 2019). The posted information will be updated as needed to reflect protocol amendments and study progress.

Impact of Anatomic Extent of Nodal Metastasis on Adjuvant Chemotherapy Outcomes in Stage III Colon Cancer.

BACKGROUND: An oxaliplatin-based chemotherapy regimen improves the survival outcomes of patients with stage III colon cancer. However, its complications are well-known. OBJECTIVE: The purpose of this study was to distinguish between the survival outcomes of patients who underwent curative resection for stage III colon cancer with oxaliplatin chemotherapy and those who underwent such resection without oxaliplatin chemotherapy. DESIGN: This was a retrospective analytical study based on prospectively collected data. SETTINGS: This study used data on patients who underwent surgery at our hospital between January 2010 and December 2014. PATIENTS: A cohort of 254 consecutive patients who underwent curative resection for stage III colon cancer was included in this study. The patients were divided into 2 groups: patients with isolated pericolic lymph node metastasis (n = 175) and those with extrapericolic lymph node metastasis (n = 79). MAIN OUTCOME MEASURES: Clinicopathologic features and 3-year survival outcomes were analyzed with and without oxaliplatin therapy in the pericolic lymph node group. RESULTS: The pericolic lymph node group showed significantly improved overall survival compared with the extrapericolic lymph node group at a median follow-up of 48.5 months (95.8% vs 77.8%; p < 0.001). In contrast, there was no significant difference in overall survival (99.0% vs 92.0%; p = 0.137) and disease-free survival (89.1% vs 88.2%; p = 0.460) between the oxaliplatin and nonoxaliplatin subgroups of the pericolic lymph node group. Multivariate analysis showed that the administration of oxaliplatin chemotherapy to the pericolic lymph node group did not lead to a significant difference in the overall survival (p = 0.594). LIMITATIONS: The study was limited by its retrospective design and single institutional data analysis. CONCLUSIONS: This study suggests that the anatomic extent of metastatic lymph nodes could affect patient prognosis, and the effect of oxaliplatin-based adjuvant chemotherapy may not be prominent in stage III colon cancer with isolated pericolic lymph node metastasis.