Prognostic factors of para-aortic lymph node metastasis from colorectal cancer in highly selected patients undergoing para-aortic lymph node dissection.

PURPOSE: We investigated the surgical outcomes of para-aortic lymph node (PALN) dissection in patients with colorectal cancer and assessed the prognostic factors related to the survival. METHODS: This single-center retrospective study included 31 patients with synchronous or metachronous PALN metastasis from colorectal cancer who underwent PALN dissection between January 2006 and December 2018. RESULTS: Twenty-one patients had synchronous PALN metastasis, and 10 had metachronous PALN metastasis. Seven patients had either simultaneous distant metastasis or a history of distant metastasis other than PALN metastasis at the time of PALN dissection. Eighteen patients underwent adjuvant chemotherapy. The 5-year overall and recurrence-free survival rates were 54.2 and 17.2%, respectively. A multivariable analysis revealed that rectal cancer, metachronous PALN metastasis, and three or more pathological PALN metastases were significantly poor prognostic factors for the recurrence-free survival. Among patients with rectal cancer, lower rectal cancer and lateral pelvic lymph node metastasis were poor prognostic factors for the overall survival. CONCLUSION: Curative PALN dissection for PALN metastasis from colorectal cancer is feasible with favorable long-term outcomes. A multidisciplinary approach, including surgery and chemotherapy, is needed for colorectal cancer with PALN metastasis to improve the long-term outcomes.

Lymph Node Mapping in Transverse Colon Cancer Treated Using Laparoscopic Colectomy With D3 Lymph Node Dissection.

BACKGROUND: Laparoscopic surgery for transverse colon cancer has been excluded from 7 randomized trials for various reasons. The optimal procedure for transverse colon cancer remains controversial. OBJECTIVE: This study aimed to analyze the patterns of lymph node metastasis in transverse colon cancer and to report short- and long-term outcomes of the treatment procedures. DESIGN: This was a single-center retrospective study. SETTINGS: This study was conducted at Cancer Institute Hospital, Tokyo, Japan. PATIENTS: We enrolled 252 patients who underwent laparoscopic surgery for transverse colon cancer. INTERVENTIONS: The transverse colon was divided into 3 segments, and the procedures for transverse colon cancer were based on these segments, as follows: right hemicolectomy, transverse colectomy, and left hemicolectomy. MAIN OUTCOME MEASURES: Postoperatively, the surgeons identified and mapped the lymph nodes from specimens and performed formalin fixation separately to compare the results of the pathological findings. RESULTS: For right-sided, middle-segment, and left-sided transverse colon cancers, the frequency of lymph node metastases was 28.2%, 19.2%, and 19.2%. Skipped lymph node metastasis occurred in right-sided and left-sided transverse colon cancers but not in middle-segment transverse colon cancers. The pathological vascular invasion rate was significantly higher in right and left hemicolectomy than in transverse colectomy. For right hemicolectomy, transverse colectomy, and left hemicolectomy, 5-year overall survival rates were 96.3%, 92.7%, and 93.7%, and relapse-free survival rates were 92.4%, 88.3%, and 95.5%. In multivariate analysis, the independent risk factor for relapse-free survival was lymph node metastasis. LIMITATIONS: Selection bias and different backgrounds may have influenced surgical and long-term outcomes. CONCLUSION: Laparoscopic surgery for transverse colon cancer may be a feasible technique. Harvested lymph node mapping after laparoscopic resection based on D3 lymphadenectomy may help guide the field of dissection when managing patients who have transverse colon cancer. The only independent prognostic factor for relapse-free survival was node-positive cancer. See Video Abstract at http://links.lww.com/DCR/B706.MAPEO DE GANGLIOS LINFÁTICOS EN CÁNCER DE COLON TRANSVERSO TRATADO MEDIANTE COLECTOMÍA LAPAROSCÓPICA CON LINFADENECTOMÍA D3ANTECEDENTES:La cirugía laparoscópica en casos de cáncer de colon transverso fué excluida de siete estudios randomizados mayores por diversas razones. El procedimiento más idóneo en casos de cáncer de colon transverso, sigue siendo controvertido.OBJETIVO:Analizar los patrones de las metástasis en los ganglios linfáticos en casos de cáncer de colon transverso y reportar los resultados a corto y largo plazo de los diferentes procedimientos para su tratamiento.DISEÑO:Estudio retrospectivo en un solo centro de referencia.AJUSTE:Estudio llevado a cabo en el Hospital del Instituto del Cancer, Tokio, Japón.PACIENTES:Fueron incluidos 252 pacientes, sometidos a cirugía laparoscópica por cáncer de colon transverso.INTERVENCIONES:El colon transverso fué dividido en tres segmentos y los procedimientos en casos de cáncer se basaron sobre estos segmentos del tranverso, de la siguiente manera: hemicolectomía derecha, colectomía transversa y hemicolectomía izquierda.PRINCIPALES MEDIDAS DE RESULTADO:En el postoperatorio, los cirujanos identificaron y mapearon los ganglios linfáticos de las piezas quirúrgicas y las fijaron con formaldehido por separado para así poder comparar los resultados con los hallazgos histopatológicos.RESULTADOS:En los cánceres de colon transverso del segmento derecho, del segmento medio y del segmento izquierdo, la frecuencia de metástasis en los ganglios linfáticos fue del 28,2%, 19,2% y 19,2%, respectivamente. Las metástasis en los ganglios linfáticos omitidos se produjo en los cánceres de colon transverso del lado derecho y del lado izquierdo, pero no en los cánceres de colon transverso del segmento medio. La tasa de invasión vascular patológica fue significativamente mayor en la hemicolectomía derecha e izquierda que en la colectomía transversa. Para la hemicolectomía derecha, colectomía transversa y hemicolectomía izquierda, las tasas de supervivencia general a cinco años fueron del 96,3%, 92,7% y 93,7%, y las tasas de supervivencia sin recaída fueron del 92,4%, 88,3% y 95,5%, respectivamente. En el análisis multivariado, el factor de riesgo independiente para la sobrevida sin recidiva fue la metástasis en los ganglios linfáticos.LIMITACIONES:El sesgo de selección y los diferentes antecedentes pueden haber influido en los resultados quirúrgicos a largo plazo.CONCLUSIONES:La cirugía laparoscópica en casos de cáncer de colon transverso puede ser una técnica factible. El mapeo de los ganglios linfáticos recolectados después de la resección laparoscópica basada en la linfadenectomía D3 puede ayudar a guiar el campo de la disección en el manejo de pacientes con cáncer de colon transverso. El único factor pronóstico independiente para el SLR fue el cáncer con ganglios positivos. Consulte Video Resumen en http://links.lww.com/DCR/B706. (Traducción-Dr. Xavier Delgadillo).

Short- and long-term outcomes of laparoscopic surgery with extracorporeal anastomosis for transverse colon cancer: comparison of triangulating anastomosis with functional end-to-end anastomosis.

BACKGROUND: We compared triangulating anastomosis (TRI) with functional end-to-end anastomosis (FEEA) in terms of patient demographics, clinicopathological features, and short- and long-term outcomes in this study. METHODS: From November 2005 to May 2016, 315 patients with transverse colon cancer underwent laparoscopic resection. TRI was performed in 62 patients and FEEA in 253 patients. Patients with another concomitant cancer, who received neoadjuvant chemotherapy, and/or who underwent another operation at the same time were excluded. RESULTS: The patients' backgrounds were comparable in each group. Transverse colectomy was selected more frequently in TRI and right hemicolectomy in FEEA. The operation time was shorter in TRI. The rate of anastomotic leakage was comparable (1.6% in TRI vs. 0.8% in FEEA). Stricture was more common in TRI (8.1% vs. 0%) and bleeding was more common in FEEA (1.6% vs. 10.6%). The rate of long-term complications was comparable in each group. Overall survival of stage 0-III patients was comparable in each group (94.7% in TRI vs. 93.7% in FEEA). 5-year disease-free survival of stage 0-III, stage II, and stage III patients was also comparable in each group (94.8% vs. 93.0%, 100% vs. 92.1%, and 80.3% vs. 79.2% in TRI and FEEA, respectively). CONCLUSION: The short- and long-term outcome rates were acceptable in both groups. Specific attempts to prevent complications are required for each anastomotic procedure.

Decision-making in postoperative chemotherapy for ovarian metastasis from colorectal cancer: a retrospective single-center study.

BACKGROUND: Ovarian metastases from colorectal cancer are relatively uncommon, and no consensus has been reached regarding resection of metastases or chemotherapy before and after surgery. We evaluated the clinicopathological characteristics of ovarian metastases from colorectal cancer and the impact of metastatic resection. We also performed a comparative analysis to clarify the prognostic impact of metastatic resection and the choice of chemotherapy before and after surgery. METHODS: Between 2006 and 2014, 38 patients at our institution underwent resection of ovarian metastases from colorectal cancer. Clinicopathological data were extracted from the patients' records and evaluated with respect to the long-term outcome. For 15 patients with metachronous ovarian metastases who received chemotherapy until immediately before resection, we compared the prognosis with and without changes in the regimen after resection. RESULTS: The 5-year overall survival rate was 19.9%, and the median survival duration was 27.2 months. The survival rate in the R0 resection group (n = 8) was significantly better than that in the R1/2 resection group (n = 30) (P = 0.0004). Patients without peritoneal dissemination (n = 15) or extra-ovarian metastases (n = 31) had a significantly better prognosis than those with peritoneal dissemination (n = 23) or extra-ovarian metastases (n = 7) (P = 0.040 and P = 0.0005, respectively). The progression-free survival and median survival times of patients who resumed chemotherapy after resection without a change in their preoperative regimen were 10.2 months and 26.2 months, respectively, while those among patients with a change in their regimen before resection versus after resection were 11.0 months and 18.1 months, respectively. The difference between the two groups was not statistically significant (progression-free survival time and median survival time: P = 0.52 and P = 0.48, respectively). CONCLUSIONS: Patients who underwent R0 resection of ovarian metastases clearly had a better prognosis than those who underwent R1/2 resection. Additionally, a poor prognosis was associated with the presence of peritoneal dissemination and extra-ovarian metastases. The data also suggested that resumption of chemotherapy without changing the regimen after resection could preserve the next line of chemotherapy for future treatment and improve the prognosis.

T-cell complexity and density are associated with sensitivity to neoadjuvant chemoradiotherapy in patients with rectal cancer.

Emerging evidence suggests that an increased density of pre-treatment CD8+ tumor-infiltrating lymphocytes (TILs) is associated with good response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. However, the significance of T-cell complexity in the clinical setting remains unknown. High-throughput T-cell receptor (TCR) ß sequencing was applied to quantify the TCR repertoire of pre-treatment biopsies from 67 patients with advanced rectal cancer receiving preoperative CRT. Diversity index was used to represent the complexity of the TCR repertoire in a tumor. Pre-treatment CD8+ TIL densities were assessed by immunohistochemistry. Changes in TCR repertoire before and after CRT were also analysed in 23 patients. Diversity indices were significantly higher for good responders than for non-responders (P = 0.031). The multivariate analysis revealed that both CD8+ TIL density and TCR diversity index were independently associated with good response to CRT (P < 0.001 and P = 0.049, respectively). Patients who were high for both CD8+ TIL density and TCR diversity (double-high) had markedly better responses to CRT than double-low patients (84.2% vs 16.7%, P < 0.0001). Larger changes in TCR repertoires before and after CRT were correlated with better recurrence-free survival (P = 0.027). The complexity and dynamic change in the TCR repertoire might serve as a useful indicator of response to CRT in combination with CD8+ TIL density in patients with rectal cancer.

Systemic Inflammatory Markers Combined with Tumor-Infiltrating Lymphocyte Density for the Improved Prediction of Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer.

BACKGROUND: Previous studies have reported the utility of systemic inflammatory markers and CD8+ tumor-infiltrating lymphocyte (TIL) separately in predicting response to chemoradiotherapy (CRT) in rectal cancer; however, the efficacy of combining these markers remains unclear. OBJECTIVE: This study aimed to elucidate the predictive efficacy of systemic inflammatory markers combined with CD8+ TIL density on response to neoadjuvant CRT in locally advanced rectal cancer. METHODS: Ten systemic inflammatory markers and CD8+ TIL density were assessed in 267 patients with rectal cancer using pretreatment clinical data and biopsy samples. Response to CRT was determined using the Dworak tumor regression grade (TRG), with good responders classified as TRG3-4. RESULTS: Receiver operating characteristic curve analysis showed high areas under the curve for the lymphocyte-to-C-reactive protein ratio (LCR) and neutrophil × monocyte (N × M) value (0.58 and 0.62, respectively). In the multivariate analysis, LCR, N × M value, and CD8+ TIL density were independently associated with good responders (p = 0.016, 0.005, and 0.002, respectively). Stratified analysis with these three markers showed a positive correlation between TRG3-4 ratio and the number of positive predictive factors (8.2%, 20.0%, 34.2%, and 59.1% in patients with 0, 1, 2, and 3 predictors, respectively). Overall and disease-free survival were significantly worse in patients with zero factors present compared with those with one to three factors present. CONCLUSIONS: LCR, N × M value, and CD8+ TIL density are independently associated with response to CRT. Assessing local TIL density along with systemic inflammatory markers may be useful for selecting a multimodal neoadjuvant approach in rectal cancer therapy.

Adding Narrow-Band Imaging to Chromoendoscopy for the Evaluation of Tumor Response to Neoadjuvant Therapy in Rectal Cancer.

BACKGROUND: Endoscopic assessment is crucial in diagnosing clinical complete response after neoadjuvant therapy in rectal cancer. OBJECTIVE: The purpose of this research was to evaluate the benefits of adding narrow-band imaging endoscopy to conventional chromoendoscopy in predicting pathologic complete response in the surgical specimen. DESIGN: This was a prospective nonrandomized study. SETTINGS: This was an ad hoc study of a prospective phase II trial at a single comprehensive cancer center that evaluated oncologic outcomes of a neoadjuvant therapy for rectal cancer. PATIENTS: Patients with high-risk stage II to III low rectal cancer who received neoadjuvant modified folinic acid, fluorouracil, and oxaliplatin plus bevacizumab followed by chemoradiotherapy and surgery were included. INTERVENTION: Tumor response after neoadjuvant therapy was evaluated using conventional white light endoscopy plus chromoendoscopy then followed by using narrow-band imaging based on a predefined diagnostic protocol. MAIN OUTCOME MEASURES: Diagnostic accuracy for predicting pathologic complete response and inter-rater agreement between an expert and trainee endoscopists were compared between the assessments using conventional white light endoscopy plus chromoendoscopy and the assessment adding narrow-band imaging. RESULTS: In total, 61 patients were eligible for the study, and 19 had pathologic complete response (31.1%). Although the addition of narrow-band imaging correctly converted the diagnosis in 3 patients, overall diagnostic improvement in predicting pathologic complete response was limited (conventional chromoendoscopy vs adding narrow-band imaging: accuracy, 70.5% vs 75.4%; sensitivity, 63.2% vs 73.7%; specificity, 73.8% vs 76.2%; positive predictive value, 52.2% vs 58.3%; and negative predictive value, 81.6% vs 86.5%). A κ value for the inter-rater agreement improved from 0.599 to 0.756 by adding narrow-band imaging. LIMITATIONS: This was a single-center study with a relatively small sample size. CONCLUSIONS: Despite the limited improvement in diagnostic accuracy, adding narrow-band imaging to chromoendoscopy improved inter-rater agreement between the expert and nonexpert endoscopists. Narrow-band imaging is a reliable and promising modality for universal standardization of the diagnosis of clinical complete response. See Video Abstract at http://links.lww.com/DCR/B275. ADICIÓN DE IMÁGENES DE BANDA ESTRECHA A LA CROMOENDOSCOPÍA PARA LA EVALUACIÓN DE LA RESPUESTA TUMORAL A LA TERAPIA NEOADYUVANTE EN EL CÁNCER DE RECTO: La evaluación endoscópica es fundamental para valorar la respuesta clínica completa después de la terapia neoadyuvante en el cáncer de recto.Evaluar los beneficios de agregar endoscopia de imagen de banda estrecha a la cromoendoscopía convencional para predecir la respuesta patológica completa en la muestra quirúrgica.Estudio prospectivo no aleatorizado.Un estudio ad hoc de un ensayo prospectivo de fase II en un solo centro integral de cáncer que evaluó los resultados oncológicos de una terapia neoadyuvante para el cáncer rectal.Pacientes con cáncer rectal bajo de alto riesgo en estadio II-III que recibieron ácido folínico neoadyuvante modificado, fluorouracilo y oxaliplatino más bevacizumab seguido de quimiorradioterapia y cirugía.La respuesta tumoral después de la terapia neoadyuvante se evaluó mediante endoscopia de luz blanca convencional más cromoendoscopía, seguido de imágenes de banda estrecha basadas en un protocolo de diagnóstico predefinido.La precisión diagnóstica para predecir la respuesta patológica completa y el acuerdo entre evaluadores entre un experto y un endoscopista en entrenamiento se compararon entre las evaluaciones utilizando endoscopia de luz blanca convencional más cromoendoscopía y la evaluación agregando imágenes de banda estrecha.En total, 61 pacientes fueron elegibles para el estudio, y 19 tuvieron una respuesta patológica completa (31.1%). Aunque la adición de imágenes de banda estrecha convirtió correctamente el diagnóstico en 3 pacientes, la mejora diagnóstica general en la predicción de la respuesta patológica completa fue limitada (cromoendoscopía convencional versus adición de imágenes de banda estrecha: precisión, 70.5% versus 75.4%; sensibilidad, 63.2% versus 73.7%; especificidad, 73.8% versus 76.2%; valor predictivo positivo, 52.2% versus 58.3%; y valor predictivo negativo, 81.6% versus 86.5%). Un valor de kappa para el acuerdo entre evaluadores mejoró de 0.599 a 0.756 al agregar imágenes de banda estrecha.Un estudio de centro único con un tamaño de muestra relativamente pequeño.A pesar de la mejora limitada en la precisión diagnóstica, agregar imágenes de banda estrecha a la cromoendoscopía mejoró el acuerdo entre evaluadores entre los endoscopistas expertos y no expertos. La imagenología de banda estrecha es una modalidad confiable y prometedora para la estandarización universal del diagnóstico de respuesta clínica completa. Consulte Video Resumen en http://links.lww.com/DCR/B275.

Educational system for acquiring appropriate laparoscopic colorectal surgical skills: analysis in a Japanese high-volume cancer center.

BACKGROUND: Acquiring appropriate laparoscopic technique is necessary to safely perform laparoscopic surgery. The Endoscopic Surgical Skill Qualification System of the Japanese Society of Endoscopic Surgery, which was established to improve the quality of laparoscopic surgery in Japan, provides training to become an expert laparoscopic surgeon. In this study, we describe our educational system, in a Japanese highest volume cancer center, and evaluate the system according to the pass rate for the Endoscopic Surgical Skill Qualification System examination. METHODS: We assessed 14 residents who trained for more than 2 years from 2012 to 2018 in our department. All teaching surgeons, qualified by the Endoscopic Surgical Skill Qualification System, participated in all surgeries as supervisors. For the first 3 months, trainees learned as the scopist, then as the first assistant for 3 months, and then by performing laparoscopic surgery as an operator during ileocecal resection or sigmoidectomy. Trainees apply for this training in their second year of residency or later. All laparoscopic procedures in our department are standardized in detail. RESULTS: The cumulative pass rate was 75% (12/16), and 87% (12/14) of the trainees eventually passed, while the general pass rate was approximately 30%. On average, those who passed in their second or third year had experienced 94 procedures as the surgeon, 177 as the first assistant, and 199 as the scopist. The number of laparoscopic procedures and the learning curves did not differ between successful and failed applicants. CONCLUSIONS: Through our educational system, residents successfully acquired laparoscopic skills with a much higher pass rate in the Endoscopic Surgical Skill Qualification System examination than the general standard. Laparoscopic practice under supervision by experienced surgeons with standardized procedures and accurate understanding of the relevant anatomy is very helpful to achieving appropriate laparoscopic technique.

Long-term outcomes of needlescopic surgery in patients with colon cancer: a retrospective cohort study.

BACKGROUND: Laparoscopic surgery is a minimally invasive and frequently performed surgical procedure that has become the standard surgery for colorectal cancer. Needlescopic surgery (NS) for colon cancer has also been performed and reported as a less invasive technique. In this study, we investigated the long-term outcomes of NS in comparison with those of conventional surgery (CS). METHODS: The data of 1122 patients without distant metastasis who underwent laparoscopic surgery between 2011 and 2014 were retrospectively analyzed. In this study, NS was defined as a laparoscopic procedure performed with the use of 3-mm ports and forceps with one 5-mm port for an energy device, as well as with clips. One 12-mm port was placed in the umbilicus for specimen extraction from the abdominal cavity. RESULTS: A total of 241 patients underwent NS. There was no significant difference between the 5-year recurrence rate and the 5-year total mortality rate (NS: 10.0% and 5.4% vs. CS: 10.3% and 3.5%, p = 0.86/0.23). In the multivariate analysis, NS was not found to be an independent prognostic factor. In terms of the distribution of recurrence sites, there was no significant difference between the two groups. CONCLUSIONS: NS for colon cancer was not inferior to CS in terms of short-term and long-term outcomes.

Postoperative Nutritional Status is Predictive of the Survival Outcomes in Patients Undergoing Resection of Stage III Colorectal Cancer.

BACKGROUND: Preoperative nutritional status is reportedly associated with the clinical outcomes in patients with colorectal cancer (CRC), although it remains inconclusive whether the preoperative nutritional status that may improve after surgery is truly predictive of the survival outcomes of patients with CRC. METHODS: Clinical records of patients with stage III CRC (n = 821) in whom curative resection had been achieved were retrospectively reviewed and the prognostic impact of nutritional status, determined by the controlling nutritional status (CONUT) score, was analyzed. RESULTS: The CONUT undernutrition grade was significantly associated with the overall survival rate (OS) in the original population (P < 0.0001). By adopting a cut-off value of CONUT score of ≥ 2 and adjustment for clinical variables using the inverse probability treatment weighting methods, the group with a preoperative CONUT score of ≥ 2 showed a worse OS as compared to the groups with a preoperative CONUT score of < 2 (P = 0.037). However, sub-analysis based on the dynamic changes in the CONUT score revealed that sustained malnutrition in the postoperative period was more frequent among patients with preoperative CONUT score of ≥ 2, and that the OS and recurrence-free survival rate (RFS) were significantly correlated with the "postoperative" nutritional status, irrespective of the preoperative nutritional status. Patients who showed improvements of the nutritional status after surgery showed a significantly longer OS and RFS. CONCLUSIONS: Sustained undernutrition or worsening of the nutritional status after colectomy may be associated with a worse OS and RFS after curative resection in patients with stage III CRC.

Effects of needlescopic surgery on postoperative pain in intersphincteric or abdominoperineal resection.

PURPOSE: Laparoscopic surgery allows minimally invasive treatment of rectal cancer, and needlescopic surgery (NS) offers even more minimally invasive operations beyond the scope of conventional laparoscopic surgery (CS). The aim of this study was to compare short-term outcomes of NS for intersphincteric resection (ISR) or abdominoperineal resection (APR) to treat anal or rectal cancer without an abdominal incision for specimen extraction and to measure abdominal wound pain compared to CS. METHODS: Between September 2014 and December 2016, a total of 134 patients underwent laparoscopic ISR or APR. Of these, 26 patients underwent NS, and 108 patients underwent CS. Postoperative abdominal wound pain was estimated using the numerical rating scale. Short-term outcomes were compared between NS and CS. RESULTS: No conversion to CS or open surgery was required. Median operation time was significantly shorter with NS (295 min) than with CS (331.5 min; p = 0.020). Median estimated blood loss was significantly lower with NS (30 ml) than with CS (50 ml; p = 0.011). Postoperative pain score on postoperative day (POD)5 was significantly lower with NS than with CS (p = 0.025), and frequencies of analgesic use were significantly lower with NS than with CS on POD0, POD2, and POD3 (p = 0.032, p = 0.017, p = 0.045, respectively). The postoperative complications occurred at similar frequencies between groups (p = 0.655). CONCLUSION: NS for ISR or APR offers comparable short-term outcomes to CS, with better pain outcomes.

Improved oncologic outcomes with increase of laparoscopic surgery in modified complete mesocolic excision with D3 lymph node dissection for T3/4a colon cancer: results of 1191 consecutive patients during a 10-year period: a retrospective cohort study.

BACKGROUND: Laparoscopic modified complete mesocolic excision (mCME) with D3 lymph node dissection has been performed with increasing frequency, but the oncological safety remains unclear. This study investigated the oncological safety of laparoscopic modified CME with D3 dissection for pT3/4a M0 colon cancer. PATIENTS: Consecutive patients with pT3/4a M0 colon cancer undergoing curative colectomy at a comprehensive cancer center between 2004 and 2013 were included. Outcomes were compared between early (2004-2008, n = 450) and late (2009-2014, n = 741) periods. Prognostic factors were investigated by multivariate analysis. RESULTS: A total of 1191 patients were eligible. Median follow-up was 57 months. Laparoscopic surgeries were more common in the late period (early vs late: 53.6% vs. 91.8%, p < 0.01). Patients in the late period showed lower blood loss (20 mL vs. 10 mL, p < 0.01), higher number of harvested lymph nodes (18.1 vs. 21.6, p < 0.01) and fewer patients with < 12 harvested nodes (13.6% vs. 5.8%, p < 0.01). Postoperative complication rates were similar between periods (2.7% vs. 2.7%, p = 0.97). Five-year relapse-free survival rate (RFS) (75.3% vs. 82.7%, p < 0.01) and overall survival rate (OS) (86.9% vs. 91.7%, p = 0.01) were higher in the late period. Multivariate analysis revealed laparoscopic surgery as an independent favorable prognostic factor for both RFS (hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.54-0.99, p = 0.03) and OS (HR = 0.56, 95% CI 0.37-0.83, p < 0.01). CONCLUSION: Improved oncologic outcomes and more frequent laparoscopic surgery during the 10-year period of the study were demonstrated for modified CME with D3 dissection, suggesting the safety of this procedure performed by experienced surgeons for pT3/4a M0 colon cancer.

Serial circulating tumour DNA analysis for locally advanced rectal cancer treated with preoperative therapy: prediction of pathological response and postoperative recurrence.

BACKGROUND: The "watch-and-wait" approach is a common treatment option amongst patients with locally advanced rectal cancer (LARC). However, the diagnostic sensitivity of clinical modalities, such as colonoscopy and magnetic resonance imaging to determine pathological response, is not high. We analysed the clinical utility of circulating tumour DNA (ctDNA) of patients with LARC to predict response to preoperative therapy and postoperative recurrence. METHODS: A serial ctDNA analysis of 222 plasma samples from 85 patients with LARC was performed using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with over 240 hotspots. RESULTS: ctDNA was detected in 57.6% and 22.3% of samples at baseline and after preoperative treatment, respectively, which was significantly different (P = 0.0003). Change in ctDNA was an independent predictor of complete response to preoperative therapy (P = 0.0276). In addition, postoperative ctDNA and carcinoembryonic antigen (CEA) were independent prognostic markers for risk of recurrence after surgery (ctDNA, P = 0.0127 and CEA, P = 0.0105), with a combined analysis having cumulative effects on recurrence-free survival (P = 1.0 × 10-16). CONCLUSIONS: Serial ctDNA analysis may offer clinically useful predictive and prognostic markers for response to preoperative therapy and postoperative recurrence in patients with LARC.

Comprehensive Comparative Analysis of Prognostic Value of Systemic Inflammatory Biomarkers for Patients with Stage II/III Colon Cancer.

BACKGROUND: Among numerous systemic inflammatory biomarkers, it remains unclear which is the most prognostic for patients with stage II/III colon cancer. We aimed to compare the prognostic significance of systemic inflammatory biomarkers among patients with stage II/III colon cancer. METHODS: We included 1303 patients with stage II/III colon cancer who underwent potentially curative resection from July 2004 to December 2013. Sixteen systemic inflammatory biomarkers-derived from combinations of neutrophils, lymphocytes, monocytes, platelets, C-reactive protein (CRP), and albumin-were compared to identify the biomarker most associated with overall survival (OS) and disease-free survival (DFS) using receiver operating characteristic (ROC) curve analysis. RESULTS: Nine inflammatory biomarkers were predictive for OS, among which lymphocyte-to-CRP ratio (LCR), CRP-to-albumin ratio (CAR), neutrophil × CRP, monocyte × CRP, and platelet × CRP were also predictive for DFS. Among these five inflammatory biomarkers, the area under the curve (AUC) value was highest (0.630) for LCR, being significantly higher than that for neutrophil × CRP (P = 0.010), monocyte × CRP (P = 0.007), or platelet × CRP (P = 0.010) for OS. When the prognostic impact of LCR and CAR were analyzed by multivariate analysis, only LCR was an independent predictor of both OS [hazard ratio (HR), 1.77; 95% confidence interval (CI), 1.23-2.60; P = 0.002] and DFS (HR, 1.29; 95% CI, 1.00-1.66; P = 0.048). CONCLUSIONS: LCR may be the most useful predictive factor for OS and DFS in patients with stage II or III colon cancer.

Radiomics Approach Outperforms Diameter Criteria for Predicting Pathological Lateral Lymph Node Metastasis After Neoadjuvant (Chemo)Radiotherapy in Advanced Low Rectal Cancer.

BACKGROUND: Advanced low rectal cancer has a non-negligible risk of lateral pelvic lymph node (LPLN) metastasis (LPLNM) and lateral local recurrence (LR) after neoadjuvant (chemo)radiotherapy and total mesorectal excision. LPLN dissection (LPLND) reduces LR but increases postoperative complications and sexual/urinary dysfunction. OBJECTIVE: The aim of this study was to develop a new radiomics-based prediction model for LPLNM in patients with rectal cancer. METHODS: A total of 247 patients with rectal cancer and enlarged LPLNs treated by (chemo)radiotherapy and LPLND were enrolled in this retrospective, multicenter study. LPLN radiomic features were extracted from pretreatment portal venous-phase computed tomography images. A radiomics score of LPLN was constructed based on the least absolute shrinkage and selection operator regression in a primary cohort of 175 patients. Model performance was assessed in terms of discrimination, calibration, and decision curve analysis, and was externally validated in 72 patients. RESULTS: The radiomics score showed significantly better discrimination compared with pretreatment short-axis diameter measurements in both the primary (area under the curve [AUC] 0.91 vs. 0.83, p = 0.0015) and validation (AUC 0.90 vs. 0.80, p = 0.0298) cohorts. Decision curve analysis also indicated the superiority of the radiomics score. In a subanalysis of patients with a short-axis diameter ≥ 7 mm, the radiomics nomogram, incorporating the radiomics score and LPLN shrinkage to ≤ 4 mm, had better discrimination compared with a model incorporating only LPLN shrinkage in both cohorts. CONCLUSIONS: Radiomics-based prediction modeling provides individualized risk estimation of LPLNM in rectal cancer patients treated with (chemo)radiotherapy, and outperforms measurements of pretreatment LPLN diameter.

Feasibility of needlescopic surgery for colorectal cancer: safety and learning curve for Japanese Endoscopic Surgical Skill Qualification System-unqualified young surgeons.

BACKGROUND: Needlescopic surgery (NS) is a minimally invasive technique for colorectal cancer. NS may be easier to perform than other minimally invasive surgery such as single-incision laparoscopic surgery and natural orifice transluminal endoscopic surgery because the port setting is the same while the shafts are thinner than in conventional laparoscopic surgery. We evaluated the capability of introducing this surgery for sigmoid and rectosigmoid colon cancer by assessing the learning curve in Japanese Endoscopic Surgical Skill Qualification System (JESSQS)-unqualified surgeons. METHODS: In this retrospective study, 112 cases of sigmoidectomy and anterior resection were performed by NS from October 2011 to December 2015 in our institution. Surgical outcomes including operation time, blood loss, postoperative hospital stay, perioperative complications, and overall survival were compared between JESSQS-qualified surgeons (Group A) and JESSQS-unqualified surgeons (Group B). The learning curve for NS was established using the average operation times in JESSQS-unqualified surgeons. RESULTS: Groups A and B comprised of 41 and 71 patients, respectively. Ninety patients underwent sigmoidectomy and 22 patients underwent anterior resection. No conversion to open surgery occurred. The operation time was significantly shorter in Group A than B (P = 0.0080). There were no significant differences in blood loss, the postoperative hospital stay, perioperative complications, or overall survival between the two groups. These variables were similar even when NS was considered relatively difficult, as in patients with obesity (body mass index of ≥ 25 kg/m2), bulky tumors (tumor size of ≥ 50 mm), and stage III/IV cancer. The average operation time in JESSQS-unqualified young surgeons was significantly shorter in the ninth and tenth cases than in the first and second cases of NS (P = 0.0282). CONCLUSIONS: NS for sigmoid and rectosigmoid colon cancer was performed safely by both JESSQS-qualified surgeons and JESSQS-unqualified surgeons. Even JESSQS-unqualified young surgeons might be able to quickly learn NS techniques.

Impact of older age on clinicopathological and prognostic features of colon cancer in postmenopausal women.

To clarify the clinicopathological features of colorectal cancer in older people, systematic studies considering age, sex, and the tumor locus is needed. We focused on colon cancer in postmenopausal women (<70 years, n = 68 vs. ≥70 years, n = 85), and examined the effect of age on clinicopathological features. Rates of medullary carcinoma /mucinous carcinoma were higher and pathological stages at diagnosis were less advanced in patients ≥70 years compared with <70 years. Matching pathological stages, no significant difference in disease-free interval was observed according to age; however, disease-specific survival (DSS) was poorer in patients ≥70 years than <70 years, being significantly different in stage IV cases. Regarding post-metastasis/recurrence (met/rec) cases, chemotherapy and surgery for metastasis were less frequent in those aged ≥70 years than <70 years. Post-met/rec DSS was poorer in ≥70 years, those with microsatellite instability, and those without surgery for met/rec than in each counterpart; however, post-met/rec chemotherapy exhibited no effect. Multivariate analyses revealed that an older age and no surgery for metastasis were independent predictors of disease-specific death. These findings remained after excluding stage IV cases. Older age was a potent risk factor of rapid disease-specific death after met/rec.

Laparoscopic multivisceral resection for locally advanced colon cancer: a single-center analysis of short- and long-term outcomes.

PURPOSE: We evaluated the technical and oncological safety of laparoscopic multivisceral resection (MVR) in selected patients with locally advanced colon cancer (LACC). METHODS: We compared the clinical backgrounds, and short- and long-term outcomes of patients who underwent laparoscopic vs. those who underwent open MVR for LACC en bloc at our hospital. RESULTS: Between January, 2004 and December, 2015, 140 patients underwent MVR of the primary tumor en bloc via laparoscopic surgery (laparoscopic group; LG, n = 69) or open surgery (open group; OG, n = 71). Laparoscopic surgery was selected mainly for tumors that invaded the bladder and abdominal wall. The LG patients had smaller tumors (60 vs. 80 mm, p < 0.001), less blood loss (30 vs. 181 g, p < 0.001), and shorter hospital stays (12 vs. 19 days, p < 0.001) than the OG patients. Open conversion was required for two patients. Postoperative complications and R0 resection were comparable between the groups. Local recurrence occurred in two LG patients and two OG patients. The 5-year cancer-specific survival, disease-free survival, and local disease-free survival of patients with pT4b disease were not significantly different between the LG and OG groups (90.3% vs. 75.2%, 71.2% vs. 67.6%, and 97.1% vs. 94.2%). CONCLUSION: Although the LG included patients with lower risk, the short- and long-term outcomes were equivalent to those of the OG, which included patients with higher risk.

Laparoscopic and robotic lateral lymph node dissection for rectal cancer.

In the era of neoadjuvant chemoradiotherapy/radiotherapy and total mesorectal excision, overall oncological outcomes after curative resection of rectal cancer are excellent, with local recurrence rates as low as 5-10%. However, lateral nodal disease is a major cause of local recurrence after neoadjuvant chemoradiotherapy/radiotherapy and total mesorectal excision. Patients with lateral nodal disease have a local recurrence rate of up to 30%. The oncological benefits of lateral pelvic lymph node dissection (LPLND) in reducing local recurrence, particularly in the lateral compartment, have been demonstrated. Although LPLND is not standard in Western countries, technical improvements in minimally invasive surgery have resulted in rapid technical standardization of this complicated procedure. The feasibility and short- and long-term outcomes of laparoscopic and robotic LPLND have been reported widely. A minimally invasive approach has the advantages of less bleeding and providing a better surgical view of the deep pelvic anatomy than an open approach. With precise autonomic nerve preservation, postoperative genitourinary dysfunction has been reported to be minimal. We review recent evidence on the management of lateral nodal disease in rectal cancer and technical improvements of LPLND, focusing on laparoscopic and robotic LPLND.

Prognostic nutritional index and postoperative outcomes in patients with colon cancer after laparoscopic surgery.

PURPOSE: The prognostic nutritional index (PNI) is calculated using the serum albumin and peripheral lymphocyte counts. We sought to assess the correlation between the preoperative PNI and postoperative outcomes in patients with colon cancer treated with laparoscopic surgery. METHODS: We included 896 colon cancer patients who underwent curative laparoscopic colectomy between January 2013 and March 2016. To identify any predictors of the postoperative outcomes, we compared the clinical characteristics and immunonutritional parameters, including the PNI, between patients classified as the Clavien-Dindo grade 2 or higher (n = 99) with those classified as grade 0 or 1 (n = 797). RESULTS: A longer surgical time and a preoperative low PNI (< 49.8) (odds ratio; 1.913, p = 0.002) were independent predictors of postoperative complications according to a multivariate analysis. A preoperative low PNI was significantly associated with an older age, a lower performance status, a lower BMI, higher CEA levels, an advanced T status, lymph node metastasis, a longer operative time, a higher blood loss, a larger tumor size, treatment with a combined resection, a longer time to bowel recovery, a longer postoperative hospital stay, and a poor overall survival. CONCLUSIONS: A preoperative low PNI was found to be significantly associated with the incidence of postoperative complications, an advanced tumor status, and a poor prognosis. Further research is needed to understand how to best clinically utilize this promising parameter.