POFUT1 and PLAGL2 are characteristic markers of mucinous colorectal cancer associated with MUC2 expression.

Colorectal mucinous adenocarcinoma (MAC) is one of the most lethal histological types of colorectal cancer, and its mechanism of development is not well understood. In this study, we aimed to clarify the molecular characteristics of MAC via in silico analysis using The Cancer Genome Atlas database. The expression of genes on chromosome 20q (Chr20q) was negatively associated with the expression of MUC2, which is a key molecule that can be used to distinguish between MAC and nonmucinous adenocarcinoma (NMAC). This was consistent with a significant difference in copy number alteration of Chr20q between the two histological types. We further identified 475 differentially expressed genes (DEGs) between MAC and NMAC, and some of the Chr20q genes among the DEGs are considered to be pivotal genes used to define MAC. Both in vitro and in vivo analysis showed that simultaneous knockdown of POFUT1 and PLAGL2, both of which are located on Chr20q, promoted MUC2 expression. Moreover, these genes were highly expressed in NMAC but not in MAC according to the results of immunohistological studies using human samples. In conclusion, POFUT1 and PLAGL2 are considered to be important for defining MAC, and these genes are associated with MUC2 expression.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

The Prognostic Impact of Preoperative Osteopenia in Patients With Colorectal Cancer.

BACKGROUND: Osteopenia, a condition in which bone mineral density is lower than normal, is a noted risk factor that leads to a shortened healthy life expectancy. OBJECTIVE: To investigate the prognostic impact of preoperative osteopenia in patients with colorectal cancer. DESIGN: This was a retrospective study. SETTING: This study was conducted at a university hospital. PATIENTS: A total of 1086 patients with stage I to III colorectal cancer who underwent curative resection. MAIN OUTCOME MEASURES: Osteopenia was evaluated with CT. Overall survival, disease-specific survival, and recurrence-free survival were the primary end points. RESULTS: Osteopenia was identified in 300 patients (27.6%). Compared with the no osteopenia group, the 5-year overall survival (74.0% vs 93.4%, p < 0.001), disease-specific survival (81.6% vs 97.2%, p < 0.001), and recurrence-free survival rates (57.1% vs 88.3%, p < 0.001) were significantly lower in the osteopenia group. Multivariate analyses showed that preoperative osteopenia was significantly associated with worse overall survival (HR: 4.135; 95% CI, 2.963-5.770; p < 0.001), disease-specific survival (HR: 7.673; 95% CI, 4.646-12.675; p < 0.001), and recurrence-free survival (HR: 5.039; 95% CI, 3.811-6.662; p < 0.001). The prognosis of the osteopenia group was poorer than that of the no osteopenia group in every stage: 5-year overall survival (stage I: 89.4% vs 96.9%, p = 0.028; stage II: 76.5% vs 91.9%, p < 0.001; stage III: 56.4% vs 90.8%, p < 0.001) and 5-year recurrence-free survival (stage I: 85.4% vs 96.6%, p = 0.002; stage II: 62.0% vs 86.5%, p < 0.001; stage III: 26.4% vs 80.0%, p < 0.001). LIMITATIONS: The main limitations are retrospective single-institutional features and races of the study population. CONCLUSIONS: Preoperative osteopenia could be a strong predictive marker for long-term prognosis in colorectal cancer regardless of stage. EL IMPACTO PRONSTICO DE LA OSTEOPENIA PREOPERATORIA EN PACIENTES CON CNCER COLORRECTAL: ANTECEDENTES:La osteopenia, una afección en la que la densidad mineral ósea es más baja de lo normal, es un relevante factor de riesgo que conduce a una expectativa menor de vida saludable.OBJETIVO:Investigar el impacto pronóstico de la osteopenia preoperatoria en pacientes con cáncer colorrectal (CCR).DISEÑO:Un estudio retrospectivo.AJUSTE:Estudio realizado en un hospital universitario.PACIENTES:Un total de 1.086 pacientes con CCR en estadio I-III sometidos a una resección curativa.PRINCIPALES MEDIDAS DE RESULTADO:La osteopenia se evaluó con imágenes de tomografía computarizada. La supervivencia global la supervivencia específica de la enfermedad y la supervivencia libre de recurrencia fueron los criterios de valoración primaria.RESULTADOS:Se identificó osteopenia en 300 pacientes (27,6%). En comparación con el grupo sin osteopenia, las tasas de supervivencia global a 5 años (74,0% frente a 93,4%, p < 0,001), supervivencia especifica de la enfermedad (81,6 % frente a 97,2%, p < 0,001) tasas de supervivencia libre de recurrencia (57,1% frente a 88,3%, p < 0,001) fueron significativamente más bajas en el grupo de osteopenia. Los análisis multivariados mostraron que la osteopenia preoperatoria se asoció significativamente con una peor supervivencia global (HR 4,135; IC 95% 2,963-5,770; p < 0,001), supervivencia especifica de la enfermedad (HR 7,673; IC 95% 4,646-12,675; p < 0,001) y tasas de supervivencia libre de recurrencia (HR 5,039; IC 95% 3,811-6,662; p < 0,001). El pronóstico del grupo con osteopenia fue peor que el del grupo sin osteopenia en todos los estadios: supervivencia global a 5 años (estadio I: 89,4% frente a 96,9%, p = 0,028; estadio II: 76,5% frente a 91,9%, p < 0,001; estadio III: 56,4% frente a 90,8%, p < 0,001) y tasas de supervivencia libre de recurrencia a 5 años (estadio I: 85,4% frente a 96,6%, p < 0,002; estadio II: 62,0% frente a 86,5%, p < 0,001; estadio III: 26,4% frente a 80,0%, p < 0,001).LIMITACIONES:Las principales limitaciones son las características retrospectivas de una sola institución y las razas de la población de estudio.CONCLUSIONES:La osteopenia preoperatoria puede ser un fuerte marcador predictivo para el pronóstico a largo plazo en CCR independientemente de la etapa. (Traducción-Dr. Fidel Ruiz Healy ).

Drainage pattern of the splenic flexure vein and its accompanying arteries using three-dimensional computed tomography angiography: a single-centre study of 600 patients.

AIM: The splenic flexure has variable vascular anatomy, and the details of the venous forms are not known. In this study, we report the flow pattern of the splenic flexure vein (SFV) and the positional relationship between the SFV and arteries such as the accessory middle colic artery (AMCA). METHODS: This was a single-centre study using preoperative enhanced CT colonography images of 600 colorectal surgery patients. CT images were reconstructed into 3D angiography. SFV was defined as a vein flowing centrally from the marginal vein of the splenic flexure visible on CT. AMCA was defined as the artery feeding the left side of the transverse colon, separate from the left branch of the middle colic artery. RESULTS: The SFV returned to the inferior mesenteric vein (IMV) in 494 cases (82.3%), the superior mesenteric vein in 51 cases (8.5%) and the splenic vein in seven cases (1.2%). The AMCA was present in 244 cases (40.7%). The AMCA branched from the superior mesenteric artery or its branches in 227 cases (93.0% of cases with existing AMCA). In the 552 cases in which the SFV returned to the IMV, superior mesenteric vein or splenic vein, the left colic artery was the most frequent artery accompanying the SFV (42.2%), followed by the AMCA (38.1%) and the left branch of the middle colic artery (14.3%). CONCLUSIONS: The most common flow pattern of the vein in the splenic flexure is from the SFV to IMV. The SFV is frequently accompanied by the left colic artery or AMCA.

The Prognostic Nutritional Index is a Predictive Marker for Postoperative Complications in Patients with Late-Onset Ulcerative Colitis.

PURPOSE: The number of patients with late-onset ulcerative colitis (UC) requiring surgery has increased in recent years. The risk of postoperative complications is higher in the elderly, so preoperative assessment is important. We aimed to explore the performance of preoperative assessment of nutritional markers for predicting postoperative complications in patients with late-onset UC. METHODS: We retrospectively analysed 140 medically refractory UC patients who underwent surgery. The association between age at UC onset and risk of postoperative complications was explored using a fractional polynomial model. Uni- and multi-variate logistic regression analyses were performed to identify nutritional markers associated with postoperative complications. RESULTS: The polynomial model showed patients with UC onset after 50 years of age had an increased risk of postoperative complications. Late-onset (LO) UC, an onset occurring after 50 years old, was associated with a higher risk of incisional surgical site infection (SSI) and intra-abdominal abscess than early-onset (EO) UC. Compared with the EO group, the LO group had fewer nutritional markers that were significantly associated with postoperative complications. The prognostic nutritional index (PNI) was calculated using the albumin level and the total lymphocyte count, and it was the only index that was significant in the LO group (odds ratio 0.872 95% CI 0.77-0.99, P = 0.03). CONCLUSIONS: It was more difficult to use nutritional status to predict the risk of postoperative complications in patients with late-onset UC than in patients with early-onset ulcerative colitis. PNI may be a useful nutritional marker for patients with both late- and early-onset UC.

Prognostic Impact of Main Lymph Node Metastasis in Patients with Colon Cancer.

BACKGROUND: Although extended lymph node dissection during colon cancer surgery is recommended in both Western and Eastern countries, the perception and clinical significance of main lymph node metastasis (MLNM) remains controversial. METHODS: In total, 1557 patients with colon cancer who underwent curative resection with D3 dissection were retrospectively analyzed. Clinicopathological factors associated with MLNM were analyzed. Kaplan-Meier survival analysis and log-rank tests were used to compare the prognosis between the MLNM and non-MLNM groups. RESULTS: Multivariate analysis showed that overall survival (OS) [hazard ratio, 2.117 (0.939-4.774), p = 0.071] and recurrence-free survival (RFS) [hazard ratio, 2.183 (1.182-4.031), p = 0.013] were affected by the MLNM status independent of the TNM stage. Survival analysis demonstrated that among patients with stage III disease, the OS and RFS rates were significantly different between patients with and without MLNM (OS: p = 0.0147, RFS: p = 0.0001). However, the OS and RFS rates were not significantly different between patients who had stage III disease with MLNM and patients who had stage IV disease (OS: p = 0.5901, RFS: p = 0.9610). CONCLUSIONS: MLNM is an independent prognostic factor for patients with colon cancer. The addition of the MLNM status to the current TNM classification may enhance the prognostic value of the TNM staging system and the clinical efficacy of adjuvant therapy in patients with colon cancer.

The evaluation of postoperative bowel dysfunction in Japanese patients with rectal cancer.

PURPOSE: The present study assessed postoperative bowel dysfunction in Japanese patients with rectal cancer, including patients who underwent preoperative radiotherapy (RT). METHODS: A total of 277 rectal cancer patients who underwent primary resection were included in the analyses. A questionnaire survey was administered using the low anterior resection syndrome (LARS) score and Wexner score. Scores were determined one year after rectal surgery or diverting ileostomy closure. The LARS score was categorized as minor LARS (21-29) and major LARS (30-42). RESULTS: The proportions of patients with minor and major LARS were significantly larger and Wexner scores significantly higher in patients with distal tumors and a lower anastomosis level than in those with proximal tumors and a higher anastomosis level. Among the patients with lower rectal cancer, the proportions with minor and major LARS were similar between those with and without preoperative RT. The Wexner scores in patients with preoperative RT were significantly higher than in patients without RT. A distal tumor location and lower anastomosis level were independent risk factors of major LARS in multivariate analyses. CONCLUSION: A distal tumor location, low anastomosis level, and preoperative RT might be associated with postoperative bowel dysfunction in rectal cancer patients.

Incidence and Prognostic Value of Lavage Cytology in Colorectal Cancer.

BACKGROUND: Lavage cytology is a method to detect cancer cells released within the abdominal cavity. It has been widely utilized, in particular, for gastric cancer. However, its clinical significance has not yet been determined in colorectal cancer. OBJECTIVE: This study aimed to investigate the frequency of lavage cytology positivity and its influence on the prognosis of patients with colorectal cancer. DESIGN: This is a single-institution retrospective observational study. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: We retrospectively analyzed 3135 colorectal cancer cases from 2007 to 2013 at our institution. Intraoperative peritoneal washing cytology was performed just after the start of the operation. Fluids were centrifuged for 5 minutes at 2500 rotations per minute, cell pellets were smeared on microscope glass slides, and Papanicolaou staining was performed. MAIN OUTCOME MEASURES: The primary outcome was the 5-year overall survival rate. The secondary outcome was the 5-year recurrence rate. RESULTS: Lavage cytology positivity was detected in 19 (2.0%) and 86 (16.9%) cases of stage III and IV colorectal cancer; however, no positive cases were found in stage I and II colorectal cancer. Lavage cytology positivity was an independent prognostic factor in stage III and IV colorectal cancer in the multivariate analysis (5-year mortality HR 3.59 [1.69-7.64] in stage III, 2.23 [1.15-4.31] in stage IV). The prognosis of the 5-year survival rate was significantly worse in the lavage cytology-positive group in stages III and IV. In terms of recurrence, the results of the lavage cytology-positive group in stage III were similar to those of the lavage cytology-positive/negative group in stage IV (73.7%, 70.0%, and 75.0%). LIMITATIONS: This study was limited by its retrospective study design. CONCLUSIONS: Lavage cytology positivity is an independent prognostic and regulatory factor of stage IV colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B770.INCIDENCIA Y VALOR PRONÓSTICO EN LA CITOLOGÍA DEL LAVADO PERITONEAL EN CÁNCER COLORECTALANTECEDENTES:La citología del lavado peritoneal es un método para detectar células cancerosas liberadas dentro de la cavidad abdominal. Se ha utilizado ampliamente, en particular para el cáncer gástrico. Sin embargo, aún no se ha determinado su importancia clínica en el cáncer colorrectal.OBJETIVO:Este estudio tuvo como objetivo investigar la frecuencia de positividad de la citología del lavado y su influencia en el pronóstico de los pacientes con cáncer colorrectal.DISEÑO:Este fue un estudio observacional retrospectivo de una sola institución.DISENTORNO CLÍNICO:El estudio se llevó a cabo en un centro oncológico integral.PACIENTES:Analizamos retrospectivamente 3.135 casos de cáncer colorrectal desde 2007 hasta 2013 en nuestra institución. La citología de lavado peritoneal intraoperatorio se realizó inmediatamente después del inicio de la operación. Los fluidos se centrifugaron durante 5 min a 2.500 rpm, los sedimentos celulares se extendieron sobre portaobjetos de vidrio de microscopio y se realizó la tinción con Papanicolaou.DISPRINCIPALES MEDIDAS DE VALORACIÓN:El primer resultado fueron las tasas de supervivencia general a 5 años. El segundo resultado las tasas de recurrencia a los 5 años.RESULTADOS:Se detectó positividad en la citología de lavado en 19 (2,0%) y 86 (16,9%) casos de cáncer colorrectal en estadio III y IV, respectivamente; sin embargo, no se encontraron casos positivos en el cáncer colorrectal en estadio I y II. La positividad de la citología de lavado fue un factor pronóstico independiente en el cáncer colorrectal en estadio III y IV en el análisis multivariado [cociente de riesgo de mortalidad a 5 años 3,59 (1,69-7,64), en estadio III, 2,23 (1,15-4,31), en estadio IV]. El pronóstico de la tasa de supervivencia a 5 años fue significativamente peor en el grupo con citología de lavado positiva en los estadios III y IV. En cuanto a la recurrencia, los resultados del grupo de lavado con citología positiva en el estadio III fueron similares a los del grupo de lavado con citología positiva / negativa en el estadio IV (73,7%, 70,0% y 75,0%).LIMITACIONES:Este estudio estuvo limitado por su diseño de estudio retrospectivo.CONCLUSIONES:La positividad de la citología de lavado es un factor pronóstico y regulador independiente del cáncer colorrectal en estadio IV. Consulte Video Resumen en http://links.lww.com/DCR/B770. (Traducción- Dr. Ingrid Melo).

Real-world application of next-generation sequencing-based test for surgically resectable colorectal cancer in clinical practice.

Aim: To evaluate the significance of next-generation sequencing-based gene panel testing in surgically resectable colorectal cancer by analyzing real-world data. Materials & methods: A total of 107 colorectal cancer patients who underwent curative surgery were included, and correlations between next-generation sequencing data and clinicopathological findings were evaluated. Results: More combination patterns in gene alteration were identified in advanced-stage tumors than in early-stage tumors. The copy number alteration count was significantly lower in right-sided colon tumors and early-stage tumors. Homologous recombination deficiency was more often identified in advanced-stage tumors, and high homologous recombination deficiency status was useful for identifying high-risk stage II tumors. Conclusion: Homologous recombination deficiency was identified as a useful result of gene panel testing with novel utility in clinical practice.

The prognostic impact of preoperative mean corpuscular volume in colorectal cancer.

OBJECTIVE: The relationship between preoperative mean corpuscular volume and postoperative prognosis has been reported in some cancers recently, but no certain consensus has been reached, especially for colorectal cancer. We evaluated the usefulness of mean corpuscular volume as a prognostic factor in colorectal cancer patients. METHODS: This study included 1003 patients with colorectal cancer who underwent curative surgery in a single institution. The relationship between mean corpuscular volume values and postoperative recurrence was evaluated by fractional polynomial model. Based on the result, patients were divided into groups according to mean corpuscular volume values. Clinicopathological factors and long-term outcomes were compared between the groups. RESULTS: The risk of postoperative recurrence according to mean corpuscular volume value showed a J-shaped curve, suggesting that both low and high mean corpuscular volume have high risk. Low mean corpuscular volume (≤84 fl) group was oncologically advanced in terms of pathological tumor stage, histological grade and lymphatic invasion with higher inflammation markers. High mean corpuscular volume (>95 fl) group had higher frequency of drinking habit with higher values of aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase. Abnormal mean corpuscular volume group including these two groups showed significantly worse disease-free survival than the other (P < 0.001). Multivariate analysis suggested that abnormal mean corpuscular volume was an independent risk factor for postoperative recurrence (hazard ratio, 1.344; 95% confidence interval, 1.005-1.796; P = 0.046). Furthermore, its prognostic impact was more significant in pStage III than in other stages. CONCLUSION: Preoperative low and high mean corpuscular volume is a poor prognostic factor in colorectal cancer patients. It could be a predictive marker to estimate worse survival outcome after surgery.

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.

Horizontal spread of pericolic lymph node metastasis as a prognostic factor for recurrence in Stage III colorectal cancer.

AIM: Main lymph node (LN) metastasis dissected with a high vascular tie at the root of the feeding artery is a poor prognostic factor in colorectal cancer (CRC). However, the effects of horizontal spread on recurrence after curative resection remain unclear. The purpose of this study is to evaluate the relationship between the horizontal spread of LN metastasis and recurrence in CRC. METHOD: In this retrospective study, 189 CRC patients (98 men, 91 women) who underwent curative resection at our hospital from 2003 to 2018 and had only pericolic LN metastasis were divided into two groups: patients with LN metastasis beside the tumour only (T group, n = 121) and those with LN metastasis with horizontal spread (S group, n = 68) (mean follow-up period 50.9 ± 34.1 months). The primary outcome was recurrence-free survival (RFS). We investigated the correlation between clinicopathological background factors and recurrence using Cox regression analysis. RESULTS: Fewer than three LN metastases (N1) were found in 157 patients (107 T group, 50 S group), and four or more metastases (N2a) were found in 32 patients (14 T group, 18 S group). Univariate analyses revealed significantly shorter RFS in the S group [hazard ratio (HR) 1.95, 95% CI 1.07-3.55; p = 0.03). Multivariate analyses revealed that horizontal spread is an independent risk factor for recurrence (HR 1.95, 95% CI 1.05-3.68; p = 0.03). CONCLUSION: Although further investigation is needed, horizontal spread of LN metastasis is a prognostic factor for recurrence in Stage III CRC.

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.

Analysis of Clinicopathological Characteristics of Appendiceal Tumors in Japan: A Multicenter Collaborative Retrospective Clinical Study- A Japanese Nationwide Survey.

BACKGROUND: Appendiceal tumor has recently been treated differently from colorectal cancer. However, obtaining knowledge of this disease is difficult because of its rareness. OBJECTIVE: This study aimed to investigate the clinicopathological characteristics of appendiceal tumors in a Japanese cohort. DESIGN: This was a nationwide multi-institution retrospective observational study. SETTING: This study was conducted at the participating tertiary referral hospitals. PATIENTS: Patients with appendiceal tumor who were diagnosed between 2000 and 2017 were included. MAIN OUTCOME MEASURES: The primary outcome measured was the total survivability. RESULTS: A total of 922 patients from the 43 facilities that participated were identified. Of these, 114 patients were diagnosed with cancer other than adenocarcinomas. The remaining 760 patients, with the exception of 48 patients with unknown survival data, were eligible for the final cohort analysis. Of these 760 patients, 515 (67.8%) had mucinous adenocarcinomas and 245 (32.2%) had nonmucinous adenocarcinomas. Within the mucinous adenocarcinoma group, 267 patients (35.1%) were diagnosed as having low-grade appendiceal mucinous neoplasm. The 5-year survival rate of mucinous adenocarcinoma (83.1%) was superior to that of nonmucinous adenocarcinoma (62.0%; p < 0.01). Regarding mucinous adenocarcinoma, multivariate analysis revealed that high differentiation grade (American Joint Committee on Cancer grade 2/3), distant metastases, and R2 operation were significantly associated with a higher 5-year mortality rate. The 5-year survival rate was significantly better for low-grade appendiceal mucinous neoplasms (93.3%) than for other mucinous adenocarcinomas (72.1%; p < 0.01). LIMITATIONS: This study was limited by its retrospective study design. CONCLUSIONS: We cumulatively investigated appendiceal tumors in a multicenter retrospective study; this is the first such report from Asia. Grouping the grades as per the American Joint Committee on Cancer was useful as a prognostic indicator of appendiceal mucinous adenocarcinomas, including low-grade appendiceal mucinous neoplasm. See Video Abstract at http://links.lww.com/DCR/B282. ANÁLISIS DE LAS CARACTERÍSTICAS CLINICOPATOLÓGICAS DE LOS TUMORES APENDICULARES EN JAPÓN: UN ESTUDIO CLÍNICO RETROSPECTIVO COLABORATIVO MULTICÉNTRICO: UNA ENCUESTA NACIONAL JAPONESA: El tumor apendicular recientemente se ha tratado de manera diferente al cáncer colorrectal. Sin embargo, obtener conocimiento de esta enfermedad es difícil debido a su rareza.Este estudio tuvo como objetivo investigar las características clinicopatológicas de los tumores apendiculares en una cohorte Japonesa.Este fue un estudio observacional retrospectivo de múltiples instituciones a nivel nacional.Este estudio se realizó en los hospitales de referencia terciarios participantes.se incluyeron pacientes con tumor apendicular que fueron diagnosticados entre el 2000 y 2017.El resultado primario medido fue la supervivencia total.Se identificaron un total de 922 pacientes de las 43 instalaciones que participaron. De estos, 114 pacientes fueron diagnosticados con cáncer distinto de adenocarcinomas. Los 760 pacientes restantes, excepto 48 pacientes con datos de supervivencia desconocidos, fueron elegibles para el análisis de cohorte final. De estos 760 pacientes, 515 (67,8%) tenían adenocarcinomas mucinosos y 245 (32,2%) tenían adenocarcinomas no mucinosos. Dentro del grupo de adenocarcinoma mucinoso, 267 pacientes (35,1%) fueron diagnosticados con neoplasia mucínica apendicular de bajo grado (LAMN). La tasa de supervivencia a 5 años del adenocarcinoma mucinoso (83.1%) fue superior a la del adenocarcinoma no mucinoso (62,0%) (p <0,01). Con respecto al adenocarcinoma mucinoso, el análisis multivariado reveló que el alto grado de diferenciación (Comité Estadounidense Conjunto sobre el Cáncer grado 2/3), las metástasis a distancia y la operación R2 se asociaron significativamente con una mayor tasa de mortalidad a 5 años. La tasa de supervivencia a 5 años fue significativamente mejor para las neoplasias mucinosas apendiculares de bajo grado (93.3%) que para otros adenocarcinomas mucinosos (72,1%) (p <0,01).Este estudio fue limitado por su diseño de estudio retrospectivo.Investigamos acumulativamente los tumores apendiculares en un estudio retrospectivo multicéntrico y este es el primer informe de este tipo de Asia. Agrupar los grados según el Comité Estadounidense Conjunto sobre el Cáncer fue útil como indicador pronóstico de los adenocarcinomas mucinosos apendiculares, incluida la neoplasia mucínica apendicular de bajo grado. Consulte Video Resumen en http://links.lww.com/DCR/B282. (Traducción-Dr. Yesenia Rojas-Khalil).

Interleukin-13 and its signaling pathway is associated with obesity-related colorectal tumorigenesis.

The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6-week-old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK-Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)-13 and IL-13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL-13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL-13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti-inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL-13, could play an important role in the carcinogenesis of obesity-related CRC.

Age, Preoperative Subcutaneous Fat Area, and Open Laparotomy are Risk Factors for Incisional Hernia following Colorectal Cancer Surgery.

BACKGROUND: Although incisional hernia (IH) is a common complication of abdominal surgery, the incidence rate and risk factors are not well known. The objectives of this study are to determine the incidence rate of IH following colorectal cancer surgery and to describe the associated risk factors. METHODS: Between 2005 and 2010, patients who underwent surgery to treat colorectal cancer were examined. The diagnosis of IH was performed by CT scan, and the visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus were calculated using a 3D-image analysis system. Survival analysis was used to assess the incidence and risk factors of IH. RESULTS: A total of 626 patients (326 open, 300 laparoscopic) were included in this study, with median follow-up of 54 (range 2-97) months. Forty patients were diagnosed with postoperative IH, and the cumulative, 5-year incidence of IH was 7.3 %. Univariate analysis revealed that age, body mass index, waist circumference, hip circumference, open laparotomy, wound infection, VFA, and SFA were significantly associated with incidence of IH. Multivariate analysis revealed that age [hazard ratio (HR) 1.043 (1.005-1.083), p = 0.027], open laparotomy [HR 4.410 (1.018-19.095), p = 0.047], and SFA [HR 1.013 (1.004-1.022), p = 0.005] were significant risk factors for developing IH. CONCLUSIONS: Higher age and SFA, along with open surgery, are risk factors for developing IH.

Preoperative serum cholinesterase as a prognostic factor in patients with colorectal cancer.

Aim: Serum cholinesterase (ChE) levels are considered to reflect nutritional status. Although ChE has been well documented as a prognostic factor for some cancers, no clear consensus on its use for colorectal cancer (CRC) has been reached. The aim of this study was to investigate the relationship between preoperative serum ChE and postoperative long-term prognosis in CRC patients. Methods: A total of 1053 CRC patients who underwent curative surgery were included in this study. The correlations between the preoperative ChE value and overall survival (OS) or cancer-specific survival (CSS) were assessed. By dividing patients into two groups according to their ChE value, OS and CSS were compared between the groups. Results: Multivariate analysis revealed that the continuous ChE value was a significant predictor of OS (hazard ratio, 0.996; 95% CI, 0.993-0.998; p = 0.002) and CSS (hazard ratio, 0.994; 95% CI, 0.991-0.998; p = 0.001), independent of other variables. The low-ChE (≤234 U/L) group had a significantly poorer prognosis than the high-ChE (>234 U/L) group for both OS (5-year OS for low ChE and high ChE: 79.8% and 93.3%, respectively; p < 0.001) and CSS (5-year CSS for low ChE and high ChE: 84.8% and 95.6%, respectively; p < 0.001). Conclusions: Lower preoperative serum ChE levels are a predictive factor of poor prognosis for CRC patients. As serum ChE levels can be measured quickly and evaluated easily, ChE could become a useful marker for predicting the postoperative long-term outcomes of CRC patients.

Mesenteric location of lymph node metastasis for colorectal cancer.

BACKGROUND: The number of lymph node metastasis (LNM) is a strong prognostic factor in the treatment of colorectal cancer (CRC). However, the impact of the mesentery location on LNM remains unclear. We assessed the impact LNM location on the recurrence of stage III CRC. METHODS: Subjects with CRC and pathologically positive LNM were enrolled retrospectively. We defined three groups: LNM adjacent to the tumour (group A), metastases with horizontal or vertical spread (group B), and metastases with both horizontal and vertical spread (group C). Recurrence-free survival (RFS) was the primary outcome measure used for the study. RESULTS: A total of 241 (Group A: 121, B: 90, and C: 30) patients were recruited for the study. Multivariate analysis by Cox regression model indicated LNM location to be an independent predisposing risk factor for recurrence [group B: Hazard ratio (HR) 2.01, 95% Confidential interval (CI) 1.12-3.60, P = 0.019; group C: HR 3.00, 95% CI 1.34-6.72, P = 0.008]. Addition of mesentery spread to the N classification was significant risk factor for recurrence (mN2a: HR 2.01, 95% CI 1.07-3.78, P = 0.029; mN2b: HR 3.96, 95% CI 2.12-7.40, P < 0.01). Comparison of Harrell's C-index values was conducted, and the modified N staging risk was 0.6377, whereas the TNM N stage classification was 0.5869. CONCLUSION: Mesentery location of LNM was a risk factor and consideration of it might be beneficial for accurate prediction of CRC prognosis.

Delayed-Onset Organ/Space Surgical Site Infection Worsens Prognosis in High-Risk Stage II and III Colorectal Cancer.

BACKGROUND: It is unclear how early- and delayed-onset organ/space surgical site infections (SSIs) affect the long-term prognosis of patients with colorectal cancer, who are potential candidates for adjuvant chemotherapy. This study aimed to investigate the association between the timing of SSI onset and clinical outcome. METHODS: This retrospective, multicenter cohort study evaluated patients who were diagnosed with high-risk stage II or III colorectal cancer and underwent elective surgery between 2010 and 2020. Five-year recurrence-free survival (RFS) was the primary endpoint and was compared between early SSI, delayed SSI (divided based on the median date of SSI onset), and non-SSI groups. RESULTS: A total of 2,065 patients were included. Organ/space SSI was diagnosed in 91 patients (4.4%), with a median onset of 6 days after surgery. The early-onset SSI group had a higher proportion of patients with Clavien-Dindo grade ≥IIIb SSI than the delayed-onset SSI. Patients who received adjuvant chemotherapy (AC) had earlier organ/space SSI onset than those who did not. The adjusted hazard ratio of 5-year RFS in the delayed-onset SSI was 2.58 (95% confidence interval: 1.43-4.65; p = 0.002): higher than that in the early-onset SSI, with the non-SSI as the reference. CONCLUSIONS: Delayed-onset organ/space SSI worsened long-term prognosis compared to early-onset, and this may be due to delayed initiation of AC. Patients who are clinically suspected of having lymph node metastasis might need additional intervention to prevent delays in commencing AC due to the delayed SSI.