The impact of powered circular staplers on anastomotic leak in left-sided colorectal cancer surgeries.

BACKGROUND: Since the introduction of powered circular staplers in colorectal surgery, there has been growing interest in their impact on reducing complications, particularly anastomotic leakage. This study compared short-term postoperative outcomes between powered and manual circular staplers. METHODS: This retrospective study included colorectal cancer patients at the tertiary referral center from April to October 2023 who underwent anterior or low anterior resection (LAR) using a circular stapler. According to energy source, patients were divided into powered and manual groups, which used two powered and four types of manual staplers, respectively. All open, laparoscopic, and robotic approaches were included. Propensity score matching (PSM) analysis was used to reduce selection bias. Postoperative complications within 30 days, especially for anastomosis-related complications, were compared between the groups. RESULTS: Among 511 patients, the powered group was 161 (32%). After PSM, 143 pairs of 286 patients were analyzed. The proportions of LAR were 53.8% and 51.0%, and initial diverting stoma rates were 23.1% and 22.4% for the Powered and Manual groups, respectively. Comprehensive complication rates were similar between the Powered group and the Manual group, without statistical significance (13.3% vs. 21.0%, P = 0.063). Anastomotic leakage was not different between the Powered and Manual groups (4.2% vs. 4.9%, P = 0.782). There was no significant difference in other complications, including anastomotic bleeding, ileus, surgical site infection, and intra-abdominal hematoma. CONCLUSIONS: The study implies that powered circular staplers may not significantly reduce postoperative complications, including anastomotic leakages, compared to manual staplers in colorectal surgery of high-volume centers.

Short-term outcomes of da Vinci SP versus Xi for rectal cancer surgery: a propensity score matching analysis of two tertiary center cohorts.

BACKGROUND: This study compares the perioperative outcomes of robotic rectal cancer surgery between da Vinci single-port (SP) system, the most recent system allowing minimally invasive surgery with reduced ports, and the da Vinci Xi system. METHODS: Patients who underwent robotic surgery for rectal adenocarcinoma from January 2016 to September 2023 at two tertiary referral centers were included. A retrospective analysis was conducted to compare key parameters between patient cohorts before and after propensity score matching. RESULTS: A total of 378 patients (SP, 65 vs. Xi, 313) were analyzed. The SP group comprised a higher proportion of females (44.6% vs. 28.4%; p = 0.016) and a higher tumor location (8.25 cm vs. 6.71 cm from the anal verge; p < 0.001) than did the Xi group. SP surgery promoted a shorter total incision length (4.9 cm vs. 9.2 cm; p < 0.001), lower maximum pain scores (5 vs. 7; p < 0.001), and shorter hospital stay (6 vs. 7 days; p < 0.001) than did Xi surgery. Operation time (175 vs. 182 min; p = 0.829) and postoperative complications (9.2% vs. 12.1%; p = 0.650) did not significantly differ between the groups. Lower lying rectal tumors were more frequently treated using the Xi system than the SP system, promoting a higher diverting stoma rate (13.8% vs. 45.4%; p < 0.001) and a lower anastomosis level (4.6 cm vs. 3.3 cm; p < 0.001). After 1:1 matching, SP maintained its advantages over Xi in terms of incision length (p < 0.001), maximum pain scores (p = 0.001), and hospital stay (p < 0.001). Overall postoperative complication rates were similar between both groups (10.8% vs. 12.3%; p = 0.777). CONCLUSIONS: The da Vinci SP system continues to offer minimal invasive benefits in rectal cancer surgery. However, the Xi system's instrument diversity provides a certain advantage, particularly in cases involving low-lying rectal tumors. Tailoring robotic approaches based on individual patient characteristics remains pivotal for optimizing outcomes of rectal cancer surgery.

Risk factors for the failure of endoscopic balloon dilation to manage anastomotic stricture from colorectal surgery: retrospective cohort study.

BACKGROUND: An anastomotic stricture after colorectal surgery is principally managed by endoscopic balloon dilation (EBD). Although this intervention is effective, however, subsequent procedures or surgical interventions are often required. This study aimed to assess the long-term outcomes of EBD for anastomotic stricture arising from colorectal cancer surgery. MATERIALS AND METHODS: We analyzed 173 patients who received curative surgery for colorectal cancer at our hospital between January 2000 and December 2022 and had undergone EBD to manage anastomotic stricture. The medical records of these cases were retrospectively reviewed to assess the outcomes and risk factors for restenosis and permanent stoma. RESULTS: Of the 173 study patients, 41 (23.7%) presented with restenosis with a median time to recurrence of 49 [37-150] days. The restenosis group was significantly younger (55.6 years versus 60.8 years), with a more prominent rectal location (80.5% versus 57.6%), a higher incidence of hand-sewn anastomosis (24.4% versus 5.3%), and a higher percentage of neoadjuvant radiotherapy (34.1% versus 5.3%, P < 0.001). Multivariable analysis indicated neoadjuvant radiotherapy (adjusted HR 2.48; 95% CI 1.03-5.95) and cerebral vascular disease (adjusted HR 6.97; 95% CI 2.15-22.54) as independent prognostic factors for restenosis. Fourteen patients (8.1%) required a permanent stoma due to treatment failure. All cases needing a permanent stoma were male (14 patients, 100%, P = 0.007) and this group had a higher rate of neoadjuvant radiotherapy, adjuvant chemotherapy, and hand-sewn anastomosis. CONCLUSION: Patients receiving neoadjuvant radiotherapy are most prone to restenosis after an EBD intervention to manage an anastomotic stricture. Neoadjuvant radiotherapy is also a strong risk factor for requiring a permanent stomas due to treatment failure.

Influence of additional prophylactic oral antibiotics during mechanical bowel preparation on surgical site infection in patients receiving colorectal surgery.

BACKGROUND: Prophylactic antibiotics (PAs) are standard for preventing surgical site infections (SSIs) post-colorectal surgery. This study aims to compare the effect of additional empiric oral antibiotics (OAs) alongside routine PAs to identify SSI risk factors. METHODS: A retrospective observatory analysis was conducted from January 2019 to December 2022 at Asan Medical Center, Seoul, Korea. The cohort was divided into two groups: PA given 1 h before surgery and discontinued within 24 h, and OA administered empiric OAs during mechanical bowel preparation in addition to PA. RESULTS: From a total of 6736 patients, 3482 were in the PA group and 3254 in the OA group. SSI incidence showed no significant intergroup difference (p = 0.374) even after propensity score matching (p = 0.338). The multivariable analysis revealed male sex [odds ratio (OR): 2.153, 95% confidence interval (CI): 1.626-2.852, and p = 0.001], open surgery (OR: 3.335, 95% CI: 2.456-4.528, and p = 0.001), dirty wound (OR: 2.171, 95% CI: 1.256-3.754, and p = 0.006), and an operation time of more than 145 min (OR: 2.110, 95% CI: 1.324-3.365, and p = 0.002) as SSI risk factors. In rectal surgery subgroup, OA demonstrated a protective effect against SSI (OR: 0.613, 95% CI: 0.408-0.922, and p = 0.019) and in laparoscopic approach (OR: 0.626, 95% CI: 0.412-0.952, and p = 0.028). CONCLUSIONS: OA did not affect SSI incidence in colorectal surgeries. Male sex, open surgery, dirty wounds, and longer operation time were risk factors for SSI. However, for rectal and laparoscopic surgery, OA was a protective factor for SSI.

FDG metabolic parameter-based models for predicting recurrence after upfront surgery in synchronous colorectal cancer liver metastasis.

OBJECTIVE: This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). METHODS: In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). RESULTS: A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. CONCLUSIONS: FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. KEY POINTS: • In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

Comparative Cost Analysis Between Endoscopic Resection and Surgery for Submucosal Colorectal Cancer.

BACKGROUND: There are few studies analyzing the cost of endoscopic resection and surgical resection in the treatment of submucosal colorectal cancer. OBJECTIVE: The objective was to perform a detailed cost analysis of endoscopic resection and surgical resection for submucosal colorectal cancer. DESIGN: This was a retrospective observational study. SETTING: This study was conducted at a tertiary academic center. PATIENTS: Medical records of 484 patients with submucosal colorectal cancer who underwent endoscopic resection or surgical resection between July 2003 and July 2015 were reviewed. MAIN OUTCOME MEASUREMENTS: The total costs during index admission and follow-up as well as clinical outcomes between the 2 groups were compared in the whole cohort and propensity score-matched cohort. RESULTS: In the propensity score-matched analysis ( n = 155 in each group), the endoscopic resection and surgical resection groups did not show significant differences in the rates of procedure-related adverse events (6.5% vs 3.9%; p = 0.304) and recurrence (0.6% vs 1.3%; p > 0.99). Readmission was more common in the endoscopic resection group (40.6% vs 11.0%; p < 0.001) because 64 (41.3%) patients underwent additional surgery for endoscopic noncurative resection. The endoscopic resection group had a lower cost during the index admission (1335.6 vs 6698.4 USD; p < 0.001), whereas the surgical resection group had a lower cost during follow-up (2488.7 vs 5035.7 USD; p < 0.001). The total cumulative cost was lower in the endoscopic resection group (6371.3 vs 9187.1 USD; p < 0.001). The same trend was observed in the whole cohort without propensity score matching. LIMITATIONS: A limitation of this study was the retrospective nature of analysis. CONCLUSIONS: The total cumulative cost for treatment and follow-up for submucosal colorectal cancer was lower in the endoscopic resection group, which had comparable oncologic outcomes as the surgical resection group. Endoscopic resection can be considered a cost-effective option for initial treatment for submucosal colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B881 . ANLISIS COMPARATIVO DE COSTOS ENTRE LA RESECCIN ENDOSCPICA Y LA CIRUGA PARA EL CNCER COLORRECTAL SUBMUCOSO: ANTECEDENTES: Existen pocos estudios que analizan el costo de la resección endoscópica y la resección quirúrgica en el tratamiento del cáncer colorrectal submucoso.OBJETIVO: El objetivo fue realizar un análisis detallado de costos tanto de la resección endoscópica y la resección quirúrgica para el cáncer colorrectal submucoso.DISEÑO: Este fue un estudio observacional retrospectivo.AJUSTE: Este estudio se realizó en un centro académico terciario.PACIENTES: Se revisaron las historias clínicas de 484 pacientes con cáncer colorrectal submucoso que fueron sometidos a resección endoscópica o resección quirúrgica entre julio de 2003 y julio de 2015.PRINCIPALES MEDICIONES DE RESULTADOS: Los costos totales durante la admisión índice y el seguimiento, así como los resultados clínicos entre los dos grupos, fueron comparados en toda la cohorte y la cohorte emparejada por puntuación de propensión.RESULTADOS: En el análisis emparejado por puntuación de propensión ( n = 155 en cada grupo), los grupos de resección endoscópica y resección quirúrgica no mostraron diferencias significativas en las tasas de eventos adversos relacionados con el procedimiento (6,5% vs 3,9%, p = 0,304) y recurrencia (0,6% vs 1,3%, p > 0,99). La readmisión fue más común en el grupo de resección endoscópica (40,6% vs 11,0%, p < 0,001) porque 64 (41,3%) pacientes fueron sometidos a una cirugía adicional para lograr la resección en aquellos casos en que la resección endoscópica no fue curativa. El grupo de resección endoscópica tuvo un costo menor durante el ingreso índice (1335.6 vs 6698.4 USD, p < 0.001), mientras que el grupo de resección quirúrgica tuvo un costo menor durante el seguimiento (2488.7 vs 5035.7 USD, p < 0.001). El costo total acumulado fue menor en el grupo de resección endoscópica (6371,3 vs 9187,1 USD, p < 0,001). La misma tendencia se observó en toda la cohorte sin emparejamiento por puntuación de propensión.LIMITACIONES: La naturaleza retrospectiva del análisis.CONCLUSIONES: El costo total acumulado para el tratamiento y seguimiento del cáncer colorrectal submucoso fue menor en el grupo de resección endoscópica, que tuvo resultados oncológicos comparables a los del grupo de resección quirúrgica. La resección endoscópica puede considerarse una opción rentable para el tratamiento inicial del cáncer colorrectal submucoso. Consulte Video Resumen en http://links.lww.com/DCR/B881 . (Traducción-Dr Osvaldo Gauto ).

Optimal surgical management of duodenal fistula in Crohn's disease: a Korean multicenter cohort study.

PURPOSE: Duodenal fistula in Crohn's disease (CDF) is a rare condition with an unclear optimal surgical management approach. We reviewed a Korean multicenter cohort of CDF surgery cases and assessed their perioperative outcomes to evaluate the effectiveness of the surgical interventions. METHODS: The medical records of patients who underwent CD surgery between January 2006 and December 2021 from three tertiary medical centers were retrospectively reviewed. Only CDF cases were included in this study. The demographic and preoperative characteristics, perioperative details, and postoperative outcomes were analyzed. RESULTS: Among the initial population of 2149 patients who underwent surgery for CD, 23 cases (1.1%) had a CDF operation. Fourteen of these patients (60.9%) had a history of previous abdominal surgery, and 7 had duodenal fistula at the previous anastomosis site. All duodenal fistulas were excised and primarily repaired via a resection of the originating adjacent bowel. Additional procedures such as gastrojejunostomy, pyloric exclusion, or T-tube insertion were performed in 8 patients (34.8%). Eleven patients (47.8%) experienced postoperative complications including for anastomosis leakages. Fistula recurrence was noted in 3 patients (13%) of which one patient required a re-operation. Biologics administration was associated with fewer adverse events by multivariable analysis (P = 0.026, odds ratio = 0.081). CONCLUSION: Optimal perioperative conditioning of patients receiving a primary repair of a fistula and resection of the original diseased bowel can successfully cure CDF. Along with primary repair of the duodenum, other complementary additional procedures should be considered for better postoperative outcomes.

Clinical Implication of Perineural and Lymphovascular Invasion in Rectal Cancer Patients Who Underwent Surgery After Preoperative Chemoradiotherapy.

BACKGROUND: Lymphovascular and perineural invasion are well-known negative prognostic indicators in rectal cancer, but previous studies on their significance are not consistent. OBJECTIVE: This study assessed the prognostic value of lymphovascular and perineural invasion in rectal cancer patients who received preoperative chemoradiotherapy followed by curative resection. DESIGN: This is a retrospective analysis. SETTING: This study was performed at a tertiary cancer center. PATIENTS: Rectal cancer patients who underwent curative resection after preoperative chemoradiotherapy between January 2000 and December 2010. MAIN OUTCOME MEASURES: The primary outcomes were disease-free survival and overall survival. The survival rates were estimated using Kaplan-Meier analysis, and group comparisons were conducted using a log-rank test. RESULTS: Of the 1156 included patients, 109 (9.4%) presented with lymphovascular invasion and 137 (11.9%) presented with perineural invasion. Lymphovascular and perineural invasion were associated with T and N downstaging after preoperative chemoradiotherapy ( p < 0.001). In the ypN0 patients, the 5-year disease-free survival rates were 70.8% and 78.5% ( p = 0.150) for the lymphovascular invasion and absent groups, respectively. In the perineural invasion group, the 5-year disease-free survival rate was 59.0% compared to 80.2% in the absent group ( p = 0.001). Among the ypN+ patients, the 5-year disease-free survival rates were 36.9% and 44.4% for the lymphovascular invasion and absent groups, respectively ( p = 0.211). The perineural invasion group had a poorer 5-year disease-free survival rate compared to the absent group (29.7% vs 46.7%; p = 0.011). By multivariable analyses, perineural invasion correlated with a poor disease-free survival (HR 1.412, 95% CI 1.082-1.843; p = 0.011) and also in ypN0 subgroup analysis (HR 1.717, 95% CI 1.093-2.697; p = 0.019). LIMITATIONS: This study was a retrospective study conducted at a single center. CONCLUSIONS: Perineural invasion is a reliable independent predictor of recurrence in rectal cancer patients treated with preoperative chemoradiotherapy. Patients with perineural invasion should be considered for closer surveillance even with ypN0 status. See Video Abstract at http://links.lww.com/DCR/B833 .IMPLICACIÓN CLÍNICA DE LA INVASIÓN PERINEURAL Y LINFOVASCULAR EN PACIENTES CON CÁNCER DE RECTO SOMETIDOS A CIRUGÍA DESPUÉS DE QUIMIORRADIOTERAPIA PREOPERATORIA. ANTECEDENTES: La invasión linfovascular y perineural en cancer de recto, son indicadores pronósticos negativos bien conocidos, pero estudios previos sobre su significancia, no son consistentes. OBJETIVO: El estudio evaluó el valor pronóstico de la invasión linfovascular y perineural en pacientes con cáncer de recto sometidos a quimiorradioterapia preoperatoria seguida de resección curativa. DISEO: Es un análisis retrospectivo. ENTORNO CLINICO: El estudio se realizó en un centro oncológico terciario. PACIENTES: Pacientes con cáncer de recto sometidos a resección curativa después de quimiorradioterapia preoperatoria entre enero de 2000 y diciembre de 2010. PRINCIPALES MEDIDAS DE VALORACION: Los resultados primarios fueron la supervivencia libre de enfermedad y la supervivencia general. Las tasas de supervivencia se estimaron mediante el análisis de Kaplan-Meier y las comparaciones de grupos se realizaron mediante una prueba de rango logarítmico. RESULTADOS: De los 1156 pacientes incluidos, 109 (9,4%) presentaron invasión linfovascular y 137 (11,9%) invasión perineural. La invasión linfovascular y perineural se asoció con reducción del estadio de T y N después de la quimiorradioterapia preoperatoria ( p < 0,001). En los pacientes ypN0, las tasas de supervivencia libre de enfermedad a 5 años fueron del 70,8% y el 78,5% ( p = 0,150) para los grupos con y sin invasión linfovascular, respectivamente. En el grupo de invasión perineural, la tasa de supervivencia libre de enfermedad a 5 años fue del 59,0%, en comparación con el 80,2% en el grupo ausente ( p = 0,001). Entre los pacientes ypN +, las tasas de supervivencia sin enfermedad a 5 años fueron del 36,9% y 44,4% para los grupos con y sin invasión linfovascular, respectivamente ( p = 0,211). El grupo de invasión perineural mostró una tasa de supervivencia libre de enfermedad a 5 años menor, en comparación con el grupo ausente (29,7% versus 46,7%, p = 0,011). Mediante análisis multivariable, la invasión perineural se correlacionó con una pobre tasa de supervivencia de enfermedad (índice de riesgo 1,412; intervalo de confianza del 95%: 1,082-1,843; p = 0,011) y también en el análisis de subgrupos ypN0 (índice de riesgo 1,717; intervalo de confianza del 95%: 1,093-2,697; p = 0,019). LIMITACIONES: Estudio retrospectivo realizado en un solo centro. CONCLUSIONES: La invasión perineural es un predictor independiente y confiable de recurrencia en pacientes con cáncer de recto tratados con quimiorradioterapia preoperatoria. Los pacientes con invasión perineural deben considerarse para una vigilancia más estrecha incluso con estadio ypN0. Consulte Video Resumen en http://links.lww.com/DCR/B833 . (Traducción-Dr. Fidel Ruiz Healy ).

Comparative survival risks in patients undergoing abdominoperineal resection and sphincter-saving operation for rectal cancer: a 10-year cohort analysis using propensity score matching.

PURPOSE: Abdominoperineal resection (APR) has been considered to have a higher risk of local recurrence and poorer survival outcome than sphincter-saving operation (SSO) in patients with rectal cancer. This study compared long-term oncologic outcomes and prognostic parameters in propensity score-matched patients who underwent APR and SSO. METHODS: This study analyzed 958 consecutive patients with lower rectal cancer who underwent preoperative chemoradiotherapy followed by APR or SSO between 2005 and 2015. Propensity score matching analysis was performed to adjust baseline characteristics, including clinical stage, tumor distance from the anal verge, and tumor size. RESULTS: In the entire cohort, the APR group had larger and lower tumors and showed significantly shorter 5-year disease-free survival (DFS) than the SSO group (64.5% vs. 75.8%, p = 0.01). After propensity score matching, there were no significant between-group differences in local (9.5% vs. 8.0%, p = 0.59) and systemic (27.9% vs. 23.4%, p = 0.3) recurrence rates, and 5-year DFS (67.5% vs. 69.9%, p = 0.49) and overall survival (80.8% vs. 82.9%, p = 0.65) rates. A lower number of lymph nodes retrieved was independently associated with recurrence and survival outcomes in the APR group, whereas poorly differentiated histology was an independent associated parameter in the SSO group. Advanced stage and perineural invasion were identified as independent prognostic parameters in both groups. CONCLUSIONS: This study indicated that the long-term oncologic outcomes of APR were comparable to those of SSO. Because prognostic parameters associated with oncologic outcomes differed between the respective procedures, correctable parameters could be ameliorated through complete total mesorectal excision and personalized systemic treatment.

Oncological outcomes according to the treatment modality based on the size of rectal neuroendocrine tumors: a single-center retrospective study.

BACKGROUND: Owing to an increased number of colonoscopy screenings, the incidence of diagnosed rectal neuroendocrine tumors (NETs) has also increased. Tumor size is one of the most frequently regarded factors when selecting treatment; however, it may not be the determinant prognostic variable. We aimed to evaluate oncological outcomes according to the treatment modality based on the size of rectal NETs. METHODS: A retrospective analysis was performed on patients who were treated for rectal NETs between March 2000 and January 2016 at the Asan Medical Center, Seoul, Korea. Patients who underwent endoscopic removal, local surgical excision, and radical resection were included. The primary outcome was recurrence-free survival (RFS). Data were specified and analyzed following the 2019 World Health Organization classification (WHO). RESULTS: A total of 644 patients were categorized under three groups according to the treatment modality used: endoscopic removal (n = 567), surgical local excision (n = 56), and radical resection (n = 21). Of a total of 35 recurrences, 27 were local, whereas eight were distant. The RFS rate did not differ significantly between the treatment groups in the same tumor-size group ([Formula: see text]1 cm group: P = .636, 1-2 cm group: P = .160). For T1 tumors, RFS rate was not different between local excision and radical resection ([Formula: see text]1 cm group: P = .452, 1-2 cm group: P = .700). Depth of invasion, a high Ki-67 index, and margin involvement were confirmed as independent risk factors for recurrence. Among patients treated with endoscopic removal, endoscopic biopsy was a significant factor for worse RFS (P < .001), while tumor size did not affect the RFS. CONCLUSION: The current guideline recommends treatment options according to tumor size. However, more oncologically important prognostic factors include muscularis propria invasion and a higher Ki-67 index.

Distribution pattern of tumor infiltrating lymphocytes and tumor microenvironment composition as prognostic indicators in anorectal malignant melanoma.

Anorectal malignant melanoma (ARMM) is a rare disease with poor prognosis. Determining ARMM prognosis precisely is difficult due to the lack of proper assessment techniques. Immunotherapy has proven effective against cutaneous malignant melanoma and may show efficacy in ARMM. Herein, we assessed the immune profile of ARMM to identify possible prognostic biomarkers. Twenty-two ARMM formalin-fixed and paraffin-embedded samples were evaluated using an nCounter® PanCancer Immune Profiling Panel. Validation was performed through immunohistochemical staining for CD3, CD8, Foxp3, CD68, CD163, and PD-L1. RNA analysis revealed significantly decreased scores for pathways involved in cell regulation and function, as well as chemokines, in recurrent patients compared to nonrecurrent patients. In cell-type profiling, the recurrent cases displayed significantly low tumor infiltrating lymphocyte (TIL) scores. Recurrence/death prediction models were defined using logistic regression and showed significantly lower scores in recurrent and deceased patients (all, P < 0.001) compared to those in nonrecurrent and surviving patients. The high total TIL and tumor-associated macrophage (TAM) groups had significantly better overall survival outcomes compared to the low total TIL and TAM groups (P = 0.007 and P = 0.035, respectively). In addition, the presence of CD3 + TILs in the invasion front was an independent favorable prognostic indicator (P = 0.003, hazard ratio = 0.21, 95% confidential interval, 0.01-0.41). Patients with inflamed or brisk-infiltration type tumors also had a significantly better overall survival than that of patients with immune-desert/excluded and absent/non-brisk type tumors (P = 0.03 and P = 0.0023, respectively). In conclusion, TILs have a strong prognostic value in ARMM, and the quantification of TILs and an analysis of the TIL phenotype and infiltration pattern during pathological diagnosis are essential to guide treatment strategies and accurate prognosis in ARMM.

Re-evaluation of controversial issues in the treatment of cT3N0-2 rectal cancer: a 10-year cohort analysis using propensity-score matching.

BACKGROUND: Although neoadjuvant treatment is thought to provide optimal local control for stage II and III rectal cancers, many patients have been reported cured by total mesorectal excision (TME), alone or with additional chemotherapy (CTX). METHODS: This study retrospectively evaluated outcomes in 2643 patients with cT3N0-2 rectal cancers undergoing curative TME during 2005-2015. Recurrence and survival outcomes were measured in three propensity-score matched groups, consisting of patients who underwent preoperative chemoradiotherapy (CRT) with postoperative CTX (NAPOC), postoperative CRT (POCRT), and exclusively postoperative CTX (EPOCT). RESULTS: Near-complete or complete TME was conducted in more than 95.9% of patients and 80% of scheduled dose of postoperative CTX was completed in 99%. Except for higher SR rate in the POCRT group than the NAPOC group (p = 0.008), 5-year cumulative local and systemic recurrence (LR and SR) rates were 4.9% and 15.2% for cT3N0, and 4.2% and 21% for cT3N1-2 patients (LR, p = 0.703; SR, 0.065), respectively, with no significant differences associated with treatment exposure (p = 0.11-1). The 5-year cumulative disease-free (75.6% vs 65.7%, p = 0.018) and overall survival (87.1% vs 79.4%, p = 0.018 each) rates were higher in the NAPOC group than the POCRT group with cT3N1-2. However, any significant survival differences were not identified between the NAPOC and EPOCT groups according to tumor sub-stages or locations (p = 0.395-0.971). CONCLUSIONS: We found any treatment modalities including competent TME and postoperative adjuvant CTX efficiently reducing LR generating robust survival outcome in the propensity-matched cohorts, demanding further randomized controlled trials by clinical sub-stages II-III.

Characteristics and Prognosis of Colorectal Cancer after Liver or Kidney Transplantation.

BACKGROUND: The purpose of this study was to evaluate the characteristics and prognosis of de novo CRC patients who underwent liver or kidney transplantation. METHODS: We retrospectively reviewed the medical records of 66 de novo CRC patients selected from 8,734 liver transplant (LT) or kidney transplant (KT) recipients. We analyzed characteristics and survival outcomes of de novo CRC patients and sporadic CRC patients who underwent radical surgery with stage I-III in Asan Medical Center between 2005 and 2016. Survival outcomes were analyzed via the 1:4 matching method. RESULTS: The standard incidence ratio (SIR) of de novo CRC in KT recipients is 1.67 in men and 2.54 in women. That in LT recipients is 3.10 in men and 2.25 in women. Compared with sporadic CRC patients, de novo CRC patients had more colon cancer than rectal cancer (p=0.041). In 9 patients (13.6%), CRC was diagnosed within one year after transplantation, 21 patients (31.8%) were diagnosed between 1-5 years, and the remaining 36 patients (54.6%) were diagnosed thereafter. There were no significant differences in recurrence-free survival and overall survival between the two groups (p=0.211 and p=0.324, respectively). CONCLUSIONS: The risk of developing de novo CRC in transplant recipients was higher than in the general population. The survival outcome of de novo CRC was no different compared with the sporadic CRC. Therefore, regular surveillance is essential for timely diagnosis and treatment for transplantation patients. A large prospective study for an intense CRC surveillance program in transplantation patients is needed.

Local excision in mid-to-low rectal cancer patients who revealed clinically total or near-total regression after preoperative chemoradiotherapy; a proposed trial.

BACKGROUND: Preoperative chemoradiotherapy (pre-CRT) followed by total mesorectal excision (TME) is currently a standard therapy for locally advanced mid-to-low rectal cancer. Less aggressive, organ-preserving option such as local excision (LE) or watchful wait can alternatively be used for patients who respond well to pre-CRT. High-resolution rectal magnetic resonance imaging (MRI) is one of the most useful methods to assess pre-CRT response, and the MERCURY group has shown that the MR tumor regression grade (mrTRG) correlated with the pathologic TRG. The aim of this study is to compare postoperative complication and oncologic outcomes between LE and TME in mid-to-low rectal cancer patients whose tumors are mrTRG grade 1 (radiological complete remission) or 2 (predominant fibrosis; near-complete remission) after pre-CRT. METHODS: A prospective, double-arm, randomized, open-labeled, single center, clinical trial will be conducted in patients with mid-to-low rectal cancer whose tumors are mrTRG 1/2 after pre-CRT at the Asan Medical Center, Seoul, Korea, after approval from the Institution Review Board. Patient medical records will be de-identified using a serial number to protect personal information. Inclusion criteria will include rectal adenocarcinoma with an inferior border < 8 cm from the anal verge, mrTRG 1/2, age > 20, and provision of informed consent. Postoperative complications will be assessed by Clavien-Dindo Classification Grade. Oncologic and functional outcomes will be collected and risk factors related to these outcomes will be investigated. DISCUSSION: We believed that the rate of postoperative complication of LE will be comparable to that of TME in mid-to-low advanced rectal cancer patients with a favorable response after pre-CRT. TRIAL REGISTRATION: KCT0002579 ( https://cris.nih.go.kr ) Dec-2017.

Mechanotechnical faults and particular issues of anastomotic complications following robot-assisted anterior resection in 968 rectal cancer patients.

BACKGROUND: As most risk factors for anastomotic complications (AC) in rectal cancer patients appear to be noncorrectable, it is needed to find the correctable causes. Additionally, the outcomes of indocyanine-green fluorescence imaging (IFI) and robot-stapled anastomosis have yet been undetermined. METHODS: This study retrospectively analyzed 968 consecutive patients with rectal cancer, who underwent curative robot-assisted anterior resections between 2010 and 2018. IFI parameters and stapling features in the surgical records were reviewed, and reconfirmed. RESULTS: AC occurred in 54 patients (5.6%), 34 (3.5%) with anastomotic leakage (AL) and 24 (2.5%) with anastomotic stenosis (AS). Mechanotechnical faults including defective stapling configurations, including angles lesser than or equal to 150° and outer deviation (more than half from the center of the circle) of linear staples, between the two linear staples were independently associated with AL (P < .001 each). IFI significantly reduced AL rate (2.5% vs 5.3%, P = .029) and AS rate (2% vs 18.8%, P = .006), respectively. Robot linear stapling enabled to maintain the obtuse angle during consecutive staplings and reduced console time. AL and AS were independent risk factors for disease-free survival (P = .02) and local recurrence (P = .03), respectively. CONCLUSIONS: AC were associated with some correctable causes, namely, mechanotechnical errors and lack of use of IFI.

Local excision for ypT2 rectal cancer following preoperative chemoradiation therapy: it should not be justified.

PURPOSE: Among individuals who respond well to preoperative chemoradiation therapy (CRT) for ypT0-1, local excision (LE) could provide acceptable oncological outcomes. However, in ypT2 cases, the oncological safety of LE has not been determined. This study aimed to compare oncological outcomes between LE and total mesorectal excision of ypT2-stage rectal cancer after chemoradiation therapy and investigate the oncological safety of LE in these patients. METHODS: We included 351 patients who exhibited ypT2-stage rectal cancer after CRT followed by LE (n = 16 [5%]) or total mesorectal excision (TME) (n = 335 [95%]) after preoperative CRT between January 2007 and December 2013. After propensity matching, oncological outcomes between LE group and TME group were compared. RESULTS: The median follow-up period was 57 months (range, 12-113 months). In the LE group, local recurrence occurred more frequently (18 vs. 4%; p = 0.034) but not distant metastases (12 vs. 11%; p = 0.690). The 5-year local recurrence-free (76 vs. 96%; p = 0.006), disease-free (64 vs. 84%; p = 0.075), and overall survival (79 vs. 93%; p = 0.045) rates of the LE group were significantly lower than those of the TME group. After propensity matching, 5-year local recurrence-free survival of the LE group was significantly lower than that of the TME group (76 vs. 97%, p = 0.029). CONCLUSION: The high local failure rate and poor oncological outcomes for ypT2-stage rectal cancer patients who undergo CRT followed by LE cannot be justified as an indication for LE. Salvage surgery should be recommended in these patients.

Impact of a Multidisciplinary Team Approach for Managing Advanced and Recurrent Colorectal Cancer.

BACKGROUND: The wide variety of treatment strategies makes clinical decision-making difficult in advanced and recurrent colorectal cancer cases. Many hospitals have started multidisciplinary team (MDT) meetings comprising a team of dedicated specialists for discussing cases. MDTs for selected cases that are difficult to diagnose and treat are alternatives to regular MDTs. This study's aim was to determine the impact of a MDT for colorectal cancer on clinical decision-making. METHODS: Cases were discussed when clinical specialists had difficulty making decisions alone. All processes done by the MDT were then recorded in prospectively designed medical case forms. RESULTS: From Jan 2011 to Dec 2014, 1383 cases were discussed. A total of 549 (39.8%) case forms were completed for patients with newly diagnosed colorectal cancer, whereas 833 (60.2%) were completed for those with recurrent diseases. The MDT altered the proposed treatment of the referring physician in 179 (13%) cases. In 85 of the 179 (47.5%) altered cases, the radiologist's review of clinical information affected the diagnosis and decision. Furthermore, 152 of the 1383 MDT decisions were not implemented. Treatment intent, therapeutic plan, and alteration of decision were important reasons for not following the MDT's recommendation. CONCLUSION: Case discussions in MDT meetings resulted in altered clinical decisions in >10% cases. Implementation rates after MDT discussions might be affected by the treatment decision-making process. Imperfect decisions made by individual physicians can be decreased by the multidisciplinary decision-making process.

Prognostic and Oncologic Significance of Perineural Invasion in Sporadic Colorectal Cancer.

BACKGROUND: The presence of perineural invasion (PNI) in colorectal cancer (CRC) indicates a more aggressive phenotype, resulting in a poor prognosis. The aims of this study were to evaluate the oncologic outcome of PNI+ tumors and to investigate whether PNI status affects patient survival. METHODS: The study retrospectively enrolled 3807 patients from a single institution who underwent surgery for colorectal adenocarcinoma between January 2006 and December 2010. The patients were classified into two groups based on PNI status: PNI+ and PNI-. RESULTS: The PNI+ group included 565 patients (14.8 %) and had significantly more involved circumferential resection margins (p = 0.001) and a more advanced TNM stage (p = 0.001) than the PNI- group. Compared with the PNI- group, the PNI+ group had worse 5-year overall survival (65 vs. 88 %; p = 0.001) and 5-year disease-free survival (63 vs. 85 %; p = 0.001). Among PNI+ patients with stage IIA disease, those who received adjuvant therapy had significantly greater 5-year overall survival than those who did not (89.3 vs. 50.8 %; p = 0.001). In multivariate analyses, PNI+ was an independent negative prognostic factor for 5-year overall survival (hazard ratio [HR] 1.518, 95 % confidence interval [CI] 1.175-1.961; p = 0.001) and 5-year disease-free survival (HR 1.495, 95 % CI 1.237-1.806; p = 0.001). CONCLUSIONS: PNI positivity is an independent predictor of aggressive behavior and unfavorable prognosis in CRC. Further evaluation is needed to confirm the impact of PNI status on survival in stage IIA CRC.

Microsatellite Instability was not Associated with Survival in Stage III Colon Cancer Treated with Adjuvant Chemotherapy of Oxaliplatin and Infusional 5-Fluorouracil and Leucovorin (FOLFOX).

BACKGROUND: The impact of microsatellite instability (MSI) on survival in stage III colon cancer treated with adjuvant 5-fluorouracil-oxaliplatin combination (FOLFOX) chemotherapy is not clear. We evaluated the association between MSI and survival in this population. METHODS: We analyzed 598 patients with curatively resected stage III colon cancer treated with adjuvant FOLFOX chemotherapy. We determined MSI status using polymerase chain reaction amplification; tumors were classified as high MSI (MSI-H, ≥2 unstable markers), low MSI (MSI-L, 1 unstable marker), or microsatellite stable (MSS, no unstable marker). RESULTS: Of 598 patients, 8.4% showed MSI-H. Tumors classified as MSI-H were more commonly located in the ascending colon (54.0 vs. 27.7%, p < 0.0001) and had poorly differentiated features (32.0 vs. 8.0%, p < 0.0001). After the median follow-up of 52.8 months, 5-year disease-free (DFS) and overall survival (OS) rates were 77.0 and 85.9%, respectively. In univariate analysis, pathologic T4 (pT4) and pathologic N2 (pN2) was associated with reduced DFS (p < 0.0001 and p < 0.0001, respectively) and OS (p = 0.002 and p = 0.001, respectively), whereas MSI status did not affect either DFS (p = 0.114) or OS (p = 0.525). In patients with pN2 tumors; however, MSI-H was associated with better survival compared with MSS/MSI-L; DFS and OS in patients with MSI-H/pN2 were comparable to those in patients with pN1 tumors. CONCLUSIONS: In patients with stage III colon cancer treated with adjuvant FOLFOX, pT4 and pN2 was associated with reduced survival, but MSI status alone did not affect survival.