A prospective single-arm clinical trial to assess the safety and efficacy of monofilament polydioxanone barbed suture, MONOFIX®, on abdominal fascial closure.

BACKGROUND: For abdominal fascial closure, the choice of optimal suture material and appropriate suture technique are of paramount importance to prevent the incidence of incisional hernia. Although barbed sutures are widely used in various surgical fields, their safety and feasibility on abdominal fascial closure which requires the most tensile strength for security have not been established yet. METHODS: We conducted a prospective, single-arm, interventional clinical trial to present the postoperative outcomes of using barbed sutures in abdominal fascial closure between April 2021 and August 2021. Patients with colorectal cancer who underwent minimally invasive surgery in elective setting were included. For all participants, monofilament polydioxanone barbed suture, MONOFIX®, was used to secure the abdominal fasica. The primary outcome was the 1-year incidence of incisional hernia assessed by computed tomography. RESULTS: A total of 30 patients were included. The median fascial incision length and suture length were 6.5 cm (range, 6-7.5 cm) and 31 cm (range, 27.5-39.0 cm), respectively. The median procedure time of abdominal fascial closure was 4 min (range, 3-9 min). There was no incidence of unexpected event related to suturing including suture cutting, stopper separation from threads, and suture loosening. One case of superficial surgical site infection occurred during postoperative hospital stays. There was no fascial dehiscence, incisional hernia, and adhesive ileus during a median follow-up period of 17.5 months. CONCLUSION: Monofilament polydioxanone barbed suture, MONOFIX®, may be used safely and effectively on abdominal fascial closure. GOV NUMBER: NCT05872334.

Revised Nodal Staging Integrating Tumor Deposit Counts With Positive Lymph Nodes in Patients With Stage III Colon Cancer.

OBJECTIVE: We evaluated the prognostic value of tumor deposit (TD) counts and incorporated them with the number of positive lymph nodes to develop a revised nodal staging. SUMMARY BACKGROUND DATA: The current American Joint Committee on Cancer (AJCC) staging on colon cancer includes the TDs only for nodenegative patients, as N1c, and their counts are not considered. METHODS: We included consecutive patients with stage III colorectal cancer who underwent curative resections between January 2010 and December 2019. The patients were grouped as TD 0, TD 1, TD 2, or TD ≥3 based on their TD counts. Disease-free survival and overall survival were compared. RESULTS: Of 2446 eligible stage III patients, 658 (26.9%) had TDs. Among them, 500 (76.0%) patients concurrently had positive lymph nodes (LNs). TD counts were significantly related to worse disease-free survival (DFS) and overall survival regardless of pT stages or the number of positive LNs. The patients were restaged based on the integrated number of TD counts and positive LNs. The N3 stage, which had ≥10 integrated TDs and positive LNs, was newly classified. Among the patients who completed 6 months of adjuvant chemotherapy, those upstaged to N2 from an initial stage of N1 experienced significantly worse DFS than those confirmed as N1 in the revised N staging. The newly N3-staged patients showed significantly worse DFS than the patients initially staged as N2. CONCLUSIONS: Revised N staging using the integrated number of TD counts and positive LNs could predict DFS more accurately than current staging. It would also draw greater attention to the patients with high-risk stage III colon cancer staged as N3.

The Prognostic Value of Micropapillary Pattern in Colon Cancer and Its Role as a High-Risk Feature in Patients With Stage II Disease.

BACKGROUND: The association of a micropapillary pattern with oncologic outcomes has not been fully studied in patients with colon cancer. OBJECTIVE: We evaluated the prognostic value of a micropapillary pattern, especially for patients with stage II colon cancer. DESIGN: A retrospective comparative cohort study using propensity score matching. SETTING: This study was conducted at a single tertiary center. PATIENTS: Patients with primary colon cancer undergoing curative resection from October 2013 to December 2017 were enrolled. Patients were grouped into micropapillary pattern positive or micropapillary pattern negative. MAIN OUTCOME MEASUREMENTS: Disease-free survival and overall survival. RESULTS: Of the eligible 2192 patients, 334 (15.2%) were with micropapillary pattern (+). After 1:2 propensity score matching, 668 patients with micropapillary pattern-negative status were selected. The micropapillary pattern-positive group showed significantly worse 3-year disease-free survival (77.6% vs 85.1%, p = 0.007). Three-year overall survival of micropapillary pattern-positive and micropapillary pattern-negative patients did not show a statistically significant difference (88.9% vs 90.4%, p = 0.480). In multivariable analysis, micropapillary pattern-positive was an independent risk factor for poor disease-free survival (HR 1.547, p = 0.008). In the subgroup analysis for 828 patients with stage II disease, 3-year disease-free survival deteriorated significantly in micropapillary pattern-positive patients (82.6% vs 93.0, p < 0.001). Three-year overall survival was 90.1% and 93.9% in patients positive and negative for micropapillary pattern, respectively ( p = 0.082). In the multivariable analysis for patients with stage II disease, micropapillary pattern-positive status was an independent risk factor for poor disease-free survival (HR 2.003, p = 0.031). LIMITATIONS: Selection bias due to the retrospective nature of the study. CONCLUSIONS: Micropapillary pattern-positive status may serve as an independent prognostic factor for colon cancer, especially for patients with stage II disease. VALOR PRONSTICO DEL PATRN MICROPAPILAR Y SU PAPEL COMO CARACTERSTICA DE ALTO RIESGO EN PACIENTES CON CNCER DE COLON EN ESTADO II: ANTECEDENTES:La asociación del patrón micropapilar con los resultados oncológicos no ha sido completamente estudiada en pacientes con cáncer de colon.OBJETIVO:Evaluamos el valor pronóstico del patrón micropapilar, especialmente en pacientes con cáncer de colon en estadio II.DISEÑO:Estudio de cohortes comparativo y retrospectivo que utilize el emparejamiento por puntuación de propensiones.AJUSTE:Estudio realizado en un solo centro terciario.PACIENTES:Se incluyeron los pacientes con cáncer de colon primario sometidos a resección curativa desde octubre de 2013 hasta diciembre de 2017. Los pacientes se agruparon en patrón micropapilar positivo ( + ) o patrón micropapilar negativo ( - ).PRINCIPALES MEDIDAS DE RESULTADO:Sobrevida libre de enfermedad y la sobrevida global.RESULTADOS:De los 2192 pacientes elegibles, 334 (15,2%) tenían patrón micropapilar (+). Después de emparejar el puntaje de propensión 1:2, se seleccionaron 668 pacientes con patrón micropapilar (-). El grupo con patrón micropapilar (+) mostró una sobrevida libre de enfermedad significativamente inferior a los tres años (77,6% frente a 85,1%, p = 0,007). La sobrevida global a los tres años del patrón micropapilar (+) y del patrón micropapilar (-) no mostró una diferencia estadísticamente significativa (88,9 % frente a 90,4%, p = 0,480). En el análisis multivariable, el patrón micropapilar (+) fue un factor de riesgo independiente para una deficiente sobrevida libre de enfermedad (índice de riesgo 1,547, p = 0,008). En el análisis de subgrupos de 828 pacientes con enfermedad en estadio II, la sobrevida libre de enfermedad a los tres años se deterioró significativamente en los pacientes con patrón micropapilar (+) (82,6% frente a 93,0, p < 0,001). La sobrevida global a los tres años fué del 90,1% y del 93,9% en el patrón micropapilar (+) y el patrón micropapilar (-), respectivamente ( p = 0,082). En el análisis multivariable de los pacientes con enfermedad en estadio II, el patrón micropapilar (+) fue un factor de riesgo independiente para una sobrevida libre de enfermedad deficiente (índice de riesgo 2,003, p = 0,031).LIMITACIONES:Sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:El patrón micropapilar (+) sirve como factor pronóstico independiente para el cáncer de colon, especialmente para pacientes con enfermedad en estadio II. (Traducción-Dr. Xavier Delgadillo ).

A comparison of hand-assisted laparoscopic surgery and conventional laparoscopic surgery in rectal cancer: a propensity score analysis.

PURPOSE: The aim of this study was to compare oncologic outcomes and perioperative variables following conventional laparoscopic surgery (LAP) versus hand-assisted laparoscopic surgery (HALS) for rectal cancer. METHODS: Between January 2008 and December 2012, 2680 consecutive patients who underwent curative resection for rectal cancer were analyzed. We used 1:1 propensity score matching to adjust for potential baseline confounders between groups including age, sex, body mass index, American Society of Anesthesiologists score, tumor distance from the anal verge, clinical T and N categories, pathologic T and N categories, preoperative carcinoembryonic antigen level, and the status of preoperative concurrent chemoradiotherapy. After matching, we analyzed 278 patients in each group (n = 556). RESULTS: The median follow-up period was 36.2 and 37.4 months in the HALS group and the conventional LAP group, respectively. Postoperative complications were not significantly different between the two groups (P = 0.531). The 5-year overall survival rate was 88.8 % in the HALS group and 91.2 % in the conventional LAP group (P = 0.329). The 5-year disease-free survival rate was 77.0 % in the HALS group and 79.7 % in the conventional LAP group (P = 0.591). CONCLUSIONS: HALS is considered a safe and feasible approach for rectal cancer treatment that enables the preservation of the advantages of conventional laparoscopic surgery.

Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer.

Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions. The CpG Island Methylator PhenotypeHigh (CIMP-H) exhibited notable enrichment of microsatellite instability-high (MSI-H). Additionally, our findings indicated a significant correlation between methylation of the MLH1 gene and MSI-H status. Furthermore, we found that the CIMP-H had a higher tendency to affect the right-side of the colon tissues and was slightly more prevalent among older patients. Through our methylome profile analysis, we successfully verified the thylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundation for exploring novel molecular insights and potential therapeutic targets for the treatment of CRC. [BMB Reports 2024; 57(2): 110-115].

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

The role of transanal tube after low anterior resection in patients with rectal cancer treated with neoadjuvant chemoradiotherapy: A propensity score-matched study.

BACKGROUND: The protective efficacy of transanal tube for anastomosis was compared with that of diverting stoma in patients with rectal cancer treated with neoadjuvant chemoradiotherapy. METHODS: We included consecutive patients with rectal cancer treated with neoadjuvant chemoradiotherapy and curative surgery from January 2013 to December 2019. The patients were grouped into transanal tube or diverting stoma, according to the protection methods they received. Propensity score-matching with 1:1 ratio was done. The primary outcome was the incidence of anastomotic leakage. RESULTS: Of the 656 eligible patients, 207 (31.6%) and 385 (58.7%) patients were grouped into transanal tube and diverting stoma, respectively, and 64 (9.7%) patients who did not undergo either transanal tube or diverting stoma were excluded. After matching, the incidence of anastomotic leakage was 9.7% and 10.6% in diverting stoma and transanal tube, respectively (P = .871). The overall morbidity was 23.2% and 15.0% in diverting stoma and transanal tube, respectively (P = .045). In the multivariate analysis, tumor size >2.5 cm and level of anastomosis <4 cm were significant risk factors for anastomotic leakage. In a subgroup analysis for patients with the level of anastomosis >4 cm, the incidence of anastomotic leakage was not significantly different between the transanal tube and diverting stoma groups. However, for patients with a level of anastomosis <4 cm, the incidence of grade C anastomotic leakage was significantly greater in the transanal tube than in the diverting stoma group (2.5% vs 9.9%, P = .040). CONCLUSION: The protective efficacy of transanal tube may be comparable to diverting stoma, especially for those with a level of anastomosis >4 cm.

Early and Long-Term Outcomes after Propofol-and Sevoflurane-Based Anesthesia in Colorectal Cancer Surgery: A Retrospective Study.

BACKGROUND: Propofol is considered to protect against immunosuppression and has lower inflammatory responses in the perioperative period than volatile agents. We evaluated whether the anesthetic agent is associated with cancer outcomes. METHODS: We retrospectively reviewed 2616 patients who underwent colorectal cancer surgery under general anesthesia between 2016 and 2018 (follow-up closure: July 2021) at a single institution. Patients received propofol-based total intravenous anesthesia or sevoflurane-based inhalational anesthesia. After propensity score matching, the postoperative neutrophil-lymphocyte ratio (NLR) was compared as primary outcome, and clinical outcomes were evaluated. RESULTS: After 1:2 propensity matching, 717 patients were given propofol anesthesia and 1410 patients were given sevoflurane anesthesia. In the matched cohort, preoperative NLR was not significantly different between propofol and sevoflurane anesthesia (mean (95% CI)2.3 (1.8 to 2.8) and 2.2 (1.9 to 3.2); p = 0.72). NLR was significantly lower in propofol anesthesia at postoperative day two and five (mean difference (95% CI) 0.71 (0.43 to 0.98); p = 0.000 and 0.52 (0.30 to 0.74); p = 0.000). Urinary retention showed a higher incidence after propofol anesthesia (4.9% vs. 2.6%; p = 0.008). Other postoperative complications and overall/recurrence-free survival were not different in the two groups. DISCUSSION: Although propofol anesthesia showed lower postoperative NLR than sevoflurane anesthesia, there was no association with clinical outcomes.

Expression of SLC22A18 regulates oxaliplatin resistance by modulating the ERK pathway in colorectal cancer.

Although oxaliplatin-based chemotherapy is the current standard adjuvant therapy for colorectal cancer (CRC), the molecular mechanisms underlying oxaliplatin resistance remain unclear. Here, we examined the molecular mechanisms underlying SLC22A18-associated oxaliplatin resistance and strategies for overcoming oxaliplatin resistance. We evaluated the association between SLC22A18 and prognosis in 337 patients with CRC and its functional significance and studied the mechanisms through which SLC22A18 affects oxaliplatin resistance development in CRC cells, using CRC cell lines and patient-derived cells (PDCs). SLC22A18 downregulation was positively correlated with worse survival in patients with CRC. Low SLC22A18-expressing cells showed relatively lower sensitivity to oxaliplatin than high SLC22A18-expressing cells. In addition, ERK activation was found to be involved in the mechanisms underlying SLC22A18-related oxaliplatin resistance. To confirm ERK pathway dependence, we used an ERK inhibitor and found that combined treatment with oxaliplatin and the ERK inhibitor overcame oxaliplatin resistance in the low SLC22A18-expressing cells. Ex vivo approaches using PDC confirmed the correlation between SLC22A18 expression and oxaliplatin resistance. Results of the in vivo study showed that SLC22A18 expression regulated oxaliplatin efficacy, and that combined treatment with an ERK inhibitor could be a useful therapeutic strategy when SLC22A18 is downregulated. Together, our findings indicate that SLC22A18 could serve as a biomarker for the prediction of oxaliplatin resistance. In cases of oxaliplatin resistance due to low SLC22A18 expression, resistance can be overcome by combined treatment with an ERK inhibitor.

A Nomogram for Predicting Pathological Complete Response to Neoadjuvant Chemoradiotherapy Using Semiquantitative Parameters Derived From Sequential PET/CT in Locally Advanced Rectal Cancer.

We evaluated the predictive value of semiquantitative volumetric parameters derived from sequential PET/CT and developed a nomogram to predict pathological complete response (pCR) in patients with rectal cancer treated by neoadjuvant chemoradiotherapy (nCRT). From April 2008 to December 2013, among the patients who underwent nCRT, those who were taken sequential PET/CT before and after nCRT were included. MRI-based staging and semiquantitative parameters of PET/CT including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated before and after nCRT. Multivariable analysis was performed to select significant predictors to construct a nomogram. Sensitivity, specificity, accuracy, and area under the receiver operating characteristics curve (AUC) of the model were evaluated to determine its performance. Among 137 eligible patients, 17 (12.4%) had pCR. All post-PET/CT parameters showed significant differences between pCR and non-pCR groups. Patients were randomly assigned to a training group (91 patients) and a validation group (46 patients). In multivariable analysis with the training group, post-CEA, post-MRI T staging, post-SUVmax, and post-MTV were significantly associated with pCR. There was no significant pre-nCRT variable for predicting pCR. Using significant predictors, a nomogram was developed. Sensitivity, specificity, accuracy, and AUC of the nomogram were 0.882, 0.808, 0.848, and 0.884 with the training group and 0.857, 0.781, 0.783, and 0.828 with the validation group, respectively. This model showed the better performance than other predictive models that did not contain PET/CT parameters. A nomogram containing semiquantitative post-PET/CT could effectively select candidates for organ-sparing strategies.

Patient-derived cancer modeling for precision medicine in colorectal cancer: beyond the cancer cell line.

Since effective immunotherapeutic agents such as immune checkpoint blockade to treat cancer have emerged, the need for reliable preclinical cancer models that can evaluate and discover such drugs became stronger than ever before. The traditional preclinical cancer model using a cancer cell line has several limitations to recapitulate intra-tumor heterogeneity and in-vivo tumor activity including interactions between tumor-microenvironment. In this review, we will go over various preclinical cancer models recently discovered including patient-derived xenografts, humanized mice, organoids, organotypic-tumor spheroids, and organ-on-a-chip models. Moreover, we will discuss the future directions of preclinical cancer research.

Long-term Oncologic Outcome of Postoperative Complications After Colorectal Cancer Surgery.

PURPOSE: The impact of postoperative complications on long-term oncologic outcome after radical colorectal cancer surgery is controversial. The aim of this study was to examine the risk factors and oncologic outcomes of surgery-related postoperative complication groups. METHODS: From January 2010 to December 2010, 310 patients experienced surgery-related postoperative complications after radical colorectal cancer surgery. These stage I-III patients were classified into 2 subgroups, minor (grades I, II) and major (grades III, IV) complication groups, according to extended Clavien-Dindo classification system criteria. Clinicopathologic differences between the 2 groups were analyzed to identify risk factors for major complications. The disease-free survival rates of surgery-related postoperative complication groups were also compared. RESULTS: Minor and major complication groups were stratified with 194 patients (62.6%) and 116 patients (37.4%), respectively. The risk factors influencing the major complication group were pathologic N category and operative method. The prognostic factors associated with disease-free survival were preoperative perforation, perineural invasion, tumor budding, and receiving neoadjuvant therapy. With a median follow-up period of 72.2 months, the 5-year disease-free survival rates were 84.4% in the minor group and 78.5% in the major group, but there was no statistical significance between the minor and major groups (P = 0.392). CONCLUSION: Advanced cancer and open surgery were identified as risk factors for increased surgery-related major complications after radical colorectal cancer surgery. However, severity of postoperative complications did not affect disease-free survival from colorectal cancer.

Efficient primary culture model of patient­derived tumor cells from colorectal cancer using a Rho­associated protein kinase inhibitor and feeder cells.

In vitro culture of patient­derived tumor cells offers many advantages in the development of novel therapies for colorectal cancer. Although various culture systems have been developed, the long­term expansion of patient­derived tumor cells remains challenging. The present results suggested that tumor cells isolated from colorectal cancer patient­derived xenografts can be efficiently immortalized in conditioned medium from irradiated feeder cells containing Y­27632, a rho­associated coiled­coil containing protein kinase (ROCK) inhibitor. Patient­derived tumor cells proliferated rapidly, reaching 90­95% confluence in ~6 days. Short tandem repeat analysis suggested that these tumor tissues and cultured cells presented 13 identical short tandem repeat loci, including Amelogenin, Penta E, Penta D, D2S1338 and D19S433. Their epithelial phenotype was confirmed by staining for epithelial cell adhesion molecule and cytokeratin 20, whereas vimentin was used as a mesenchymal marker. When cells were transferred to 3D cultures, they continued to proliferate, forming well­defined tumor spheroids. Expression levels of human telomerase reverse transcriptase and C­Myc mRNA were increased in cultured cells. Finally, immortalized cells were used for the screening of 65 anticancer drugs approved by the Food and Drug Administration, allowing the identification of gene­drug associations. In the present study, primary culture models of colorectal cancer were efficiently established using a ROCK inhibitor and feeder cells, and this approach could be used for personalized treatment strategies for patients with colorectal cancer.

Treatment outcome of relapsed/refractory primary central nervous system diffuse large B-cell lymphoma: a single-center experience of autologous stem cell transplantation.

No salvage treatment strategy has been established for relapsed or refractory primary central nervous system lymphoma (PCNSL). We compared treatment outcomes of patients who underwent salvage chemotherapy with or without autologous stem cell transplantation (ASCT). We retrospectively analyzed PCNSL patients who were histologically diagnosed with diffuse large B-cell lymphoma. All patients relapsed after high-dose methotrexate (MTX)-based chemotherapy, or were refractory to high-dose MTX. Patients were treated with salvage chemotherapy, such as ICE/D (ifosfamide, carboplatin, etoposide, and dexamethasone) or high-dose MTX. High-dose chemotherapy containing thiotepa and busulfan followed by ASCT was performed if patients were eligible for ASCT after salvage treatment. Forty-five patients (35 relapsed and 10 refractory) received ICE/D or high-dose MTX. Despite the important difference that ICE/D was used predominantly for early relapsed or refractory patients, the two salvage treatments produced similar overall response rates [84.4 % (38/45) for ICE/D and 81.3 % (13/16) for high-dose MTX re-treatment]. Eighteen patients underwent ASCT, whereas 27 patients received salvage chemotherapy alone. The median progression-free survival of patients who underwent ASCT (19.5 months) was significantly better than that of patients who did not receive ASCT (6.7 months, P = 0.023). Multivariate analysis showed that refractoriness to initial treatment and no ASCT were significantly associated with poor survival outcome. Our study suggested that the combination of ifosfamide, carboplatin, etoposide, and dexamethasone may represent a feasible salvage treatment option for relapsed or refractory PCNSL, and that high-dose chemotherapy containing thiotepa and busulfan followed by ASCT may be effective for patients with a favorable toxicity profile.